Category: Vaccine

FOND DU LAC (WMTV) -- A woman in Fond du Lac who survived a harrowing brush with death is celebrating a major milestone this year. Twenty years ago, she became the first person in the world to survive rabies without receiving the life-saving vaccine.

Its almost surreal to think, you know, 20 years, said Jeanna Giese. My life changed completely when I got sick,

Back in 2004 in Fond du Lac, Giese was 15 years old. She attended church with her mother on a Sunday morning. Suddenly, a bat was spotted flying around during the service.

It flew to the back of the church and one of the ushers swatted it down, said Giese. Being an animal lover, Giese asked her mother if she could pick the bat up and take it outside. Her mother agreed.

As she was about to place the bat into a tree, Gieses life changed forever.

It did manage to stretch over and bite me in the finger and that hurt. I always get asked Did it hurt? Did you feel it? Yeah, I felt it. It hurt a lot.

Giese says she pulled the bats fang out of her left index finger. The mark on her finger was almost microscopic. She wasnt bleeding because there wasnt an open wound. Giese and her mother cleaned her finger with hydrogen peroxide and went on with their lives.

But about three weeks later, Giese began to feel extremely lethargic and nauseous.

I woke up and I could not get out of bed, my face was flush, I could hardly move, said Giese.

Her parents took her to St. Agnes Hospital in Fond du Lac. Doctors tested for meningitis and Lyme Disease, among others. Everything came back negative. Doctors were stumped as to why Giese was so sick. As her condition continued to get worse, the decision was made to transfer her to Childrens Hospital of Wisconsin in Wauwatosa.

This was actually the second time I was on call here, I knew nobody, said Dr. Rodney Willoughby. Dr. Willoughby was a pediatric doctor specializing in infectious diseases when he first met Giese. He was brand new at Childrens Hospital.

Dr. Willoughby sent samples to the Centers for Disease Control in Georgia and the diagnosis was confirmed. Giese had rabies.

Well, I thought she was going to die, said Dr. Willoughby. Thats what they all did. Thats about the extent of my knowledge of rabies at the time was that there wasnt much to do. Its really 100% fatal.

Dr. Willoughby says as this point, it was too late to administer the life-saving rabies vaccine.

The classic, conventional rabies vaccine has never failed since its introduction in the United States in the 1970s, explained Dr. Willoughby. Its probably our most efficacious and effective vaccine although fortunately, we dont have to use it often.

At this point, doctors hit a crossroads. Giese says doctors told her parents that she would either die in the hospital or they could take her home so she could die there. But Dr. Willoughby wasnt ready to give up just yet. He decided to try something experimental.

Whenever you improvise, the odds are against you, so you always worry, he said.

Dr. Willoughby decided to put Giese in a medically induced coma, a move never attempted before with a patient suffering from rabies.

He kind of came up with this idea to put me into a coma to kind of separate my brain and my body and let my own immune system fight off the virus, said Giese.

Most rabies patients die because the brain over-stimulates the heart and causes it to stop. So, the idea that we could just suppress the brain so it couldnt work as hard and so that it didnt stop the body from living -- that seemed like a reasonable idea and almost seemed too obvious, added Dr. Willoughby.

Giese laid in a coma for the next 14 days.

They didnt know if I woke up, if I was going to be me or a vegetable or anything, said Giese.

But then Giese slowly began to wake up.

He said Look over at your mom and I moved my eyes and thats when they were like Shes in there, Giese said.

Giese eventually started to move her arms and attempted to talk.

I was basically a newborn baby at the age of 15. I couldnt do anything, said Giese.

I mean, we made a lot of progress, said Dr. Willoughby. We had no idea how she was going to come out of it. We had no idea what the complications were.

Over the next few weeks and months, Giese slowly started to regain control of her life. She re-learned how to walk and underwent strenuous physical, occupational, and speech therapy.

The road to recovery was very long and painful. I dont quit. I guess its personal stubbornness, Giese said with a laugh.

Giese is now known the world over as a medical marvel. She is the first person on record to survive rabies without getting the vaccine.

Local media has covered her story extensively, including when she graduated from high school and when she became a mother. Today, she works at the Childrens Museum of Fond du Lac and is the proud mother of three children.

I always wanted to be a mom and now I am one and its just fantastic. I love my kids so much, she said.

According to Dr. Willoughby, there are just 45 known survivors of rabies. He says 18 of those survivors are from whats now called the Milwaukee Protocol.

Shes done very thing that youd want for any of your patients, so its just a total delight, said Dr. Willoughby.

All these years later, Giese is still an animal lover. Even bats. But spiders are where she draws the line.

A lot of people are astonished that I actually love bats! Giese laughed.

Shes been open about sharing her story in the hopes that she can inspire someone else who may be facing impossible odds.

I never gave up. I always wanted to try. Find that thing you believe in and never let it go, she said.

Rabies in the United States is pretty rare. The CDC says this can because of successful pet vaccination and animal control programs and public health surveillance and testing.

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20 years later, Fond du Lac woman reflects on being 1st to survive rabies without vaccine - Fox11online.com

The FDA has approved the cancer vaccine, WGc-043 (WestGene), an Epstein-Barr (EB) virus-related mRNA therapeutic cancer vaccine, for an investigational new drug (IND) application. The IND application allows the vaccine to be used in clinical trials with human subjects, which can be significant in the fight against cancers and serve as a positive advancement in cancer treatment.1

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The IND approval offers a new hope to patients who have advanced EB virus-related cancers. EB virus is highly associated with more than 10 malignancies, including different types of cancer (nasopharyngeal carcinoma [NPC], natural killer T-cell lymphoma [NKTL], as well as gastric, lung, breast, liver, esophageal, and cervical cancers) and autoimmune diseases (eg, multiple sclerosis and systemic lupus erythematosus).1

According to experts, the WGc-043 vaccine has promising efficacy, a low toxicity, broad applicability, efficient scalability, and cost effectiveness. The vaccine has already completed investigator-initiated trials that treated NPC and NKTL, and demonstrated superior efficacy and safety compared with other available mRNA therapeutic vaccines.1

Currently, a phase 1 clinical trial (NCT05714748) is recruiting participants to determine a therapeutic candidate vaccine that targets EB virus-related malignant tumors in patients who were between 18 and 70 years of age that failed second-line standard therapy. The investigators used 20 g as the starting point, and doses increased using an escalation scheme. Each participant received 1 corresponding dose, and an intramuscular injection was administered again every 7 days. After 4 doses, the fifth dose was given after a 1-month interval. The trials primary end points were frequency and number of adverse events (AEs), objective response rate, progression-free survival, and overall survival (OS).2

Another mRNA-based vaccine, mRNA-4157, showed efficacy in prolonging recurrence-free survival (RFS) in patients with resected high-risk melanoma when used in combination with pembrolizumab (Keytruda; Merck & Co) and when used as an adjuvant therapy. The randomized, open-label, phase 2 trial (NCT03897881) that mRNA-4157 plus pembrolizumab was evaluated in had also demonstrated a reduced risk of death by approximately 44% compared to pembrolizumab alone.3

At a median follow-up point of 101 and 105 weeks, recurrence or death was reported in 24 of 107 patients (22.4%) in the vaccine plus pembrolizumab arm, and in the pembrolizumab alone arm, it was 20 of 50 patients (40%). Additionally, RFS rates (95% CI) at 18 months were 78.6% (69.0%, 85.6%) in those who received the combination regimen compared with 62.2% (46.9%, 74.3%) in the monotherapy arm. The combination had also demonstrated a reduction in the risk of recurrence or death by 44% (HR = 0.561; 95% CI: (0.309, 1.017). There were no clinically meaningful AEs, according to the investigators, with treatment-related AEs reported being grade 1 or 2 in severity. The most common grade 3 AE in this trial related to mRNA-4157 was fatigue.3

Additionally, a more recent vaccine demonstrated positive improvements in survival; however, this vaccine was not mRNA-based. Similar to the prior study, this second-generation vaccine was also administered in patients who had melanoma, and the findings demonstrated positive OS rates in both the second-generation vaccine and a first-generation vaccine, but OS was better in those who received the prior. Additionally, younger men with earlier-stage melanoma were shown to benefit from vaccination more than other participants. At 10 years, OS estimates were 0.840.05 (SE) and 0.720.11 for men and women, respectively.4

The WGc-043 vaccine was developed by WestGene, a biotech company that specializes in mRNA technology. Currently, the company has a pipeline of over 20 mRNA-based therapeutic products that target a variety of diseases. If successfully launched, WGc-043 will provide a treatment option for patients who either have advanced EB virus-positive solid tumors or hematologic malignancies.1

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FDA Approves WGc-043, EB Virus-Related mRNA Therapeutic Cancer Vaccine for Use in Clinical Trials - Pharmacy Times

Children and teachers with suspected whooping cough should be excluded from classes for up to three weeks, according to official guidance.

The UK Health Security Agency (UKHSA) says youngstersshould isolate for 21 days 'from the onset of symptoms' to avoid spreading the killer bug, if they have not had antibiotics.

However, it's feared thousands of kids with minor coughs could be kept at home needlessly by worried parents, leading to a repeat of the Covid self-isolation nightmare.

Tory MP David Davis criticised the advice as overly-cautious, saying children should be tested, treated and sent back to class.

He said: 'The obvious response would be to put them on antibiotics and return them to school as quickly as possible.

'We should have learned the lesson from Covid that children are robust in the face of most illnesses. It's vitally important to maintain the continuity of education.

'Being away from school for weeks on end can put children behind in critical areas of their study, and they may not recover.

'Plainly, the right approach is to is to use medical procedures to accelerate their return, not to take an overcautious delay which could do real damage to their education.'

Whooping cough has killed five babies this year amid fears of the worst outbreak in 40 years. Almost 3,000 cases have been reported so far this year, three times the total for the whole of 2023.

The illness can be diagnosed with a PCR test and treated with antibiotics, reducing the necessary isolation time to 48 hours. But it's feared under-pressure GPs may struggle to meet demand.

Official guidance on the UKHSA website states that children should be excluded from school for at least 21 days after symptoms start. Suspected cases should be reported to them, and text messages will be sent to parents whose children attend a school with a confirmed case.

Teachers and staff at nurseries and schools should also isolate if they suffer 'active uncontrollable coughing', it adds.

A spokesman for the UKHSA said: 'If anyone in your family is diagnosed with whooping cough, it's important they stay at home and do not go into work, school or nursery until 48 hours after starting antibiotics, or 3 weeks after symptoms start if they have not had antibiotics.

'This helps to prevent the spread of infection, especially to vulnerable groups. However, vaccination remains the best protection for babies and children.'

A whooping cough vaccine for pregnant women to protect their babies was introduced in October 2012. Immediately after that, the number of baby deaths fell.

The UKHSA has blamed the current outbreak on a steady decline in the uptake of vaccines among expectant mums.Experts say this is due to a mixture of vaccine hesitancy, lack of awareness and the cancellation of many 'non essential' services during the Covid pandemic.

However, it's believed that three of the five grieving mothers had jabs during pregnancy to protect their children.

In the 1980s, the government published terrifying adverts telling parents that whooping cough can cause vomiting, weight loss, brain damage and death in children.

Dr Saleyha Ahsan, a London-based A&E doctor, said the Department of Health should go back to publicising the deadly danger of the illness to boost vaccine uptake, as they did in the 1980s and '90s.

'There is a lack of knowledge about how deadly and dangerous whooping cough can be,' she said. 'In the 1980s there was lots of coverage about how dangerous whooping cough was.

'I was a teenager then and was terrified because I had two little baby sisters. I used to bug my mum to make sure they had their vaccines because I was terrified by the pictures I was seeing.

'Publicity works. In Australia they've really gone for it, and awareness there among the general public is significantly more than here. Our vaccine uptake has gone down to about 59.5 per cent, and in some parts of London it's down to 36 per cent. Those places are the ones with worst rates of really sick babies.

'I've spoken to mums who've lost their babies to whooping cough - every one is a massive advocate for the vaccine. It's about education and reassurance. It's not all down to mums, the healthcare profession has to take a role in this.'

She added childhood whooping cough vaccines stop working after 10 years, so the NHS should consider giving boosters to adults, as they do in the US.

'Education is needed for the public, for mums, and across the healthcare profession as well, because I didn't realise it and colleagues also didn't,' she said.

'It's important. It's a highly contagious disease, it's easily spread, it's very difficult to diagnose, and if it reaches a child under two months, it can kill them. It's a discussion we need to have.'

Kerry Pearson, from Dartford, Kent, has urged all pregnant women to take the whooping cough jab after her newborn Polly spent 10 days in a coma with the infection.

In April, at just two weeks old, she developed a rattly cough that left her struggling to breathe.

She said: 'I knew nothing about whooping cough it was just something from my grandparents' era. There's no treatment and no cure, we're just having to wait and it's unbearable.

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'If I'd had the vaccine during my pregnancy I'd have passed on the antibodies in my breastmilk. The vaccine should be routinely offered with every pregnancy.

'I just want people to be aware, you should have the whooping cough vaccine when you're pregnant.If you're not offered it then please demand it.'

'If you're an anti-vaxxer please reconsider this is deadly to infants it's not worth the risk. Nothing is worth going through what we're going through.

'We need to educate people about the vaccine and the symptoms.

'Whooping cough is dangerous to newborns and I want people to know what to look out for.'

What is whooping cough?

Whooping cough is a serious and highly contagious respiratory disease that infects the lungs and breathing tubes.

Also called pertussis, it's caused by the bacteria Bordetella pertussis. After or between bouts of coughing, patients may gasp for air and produce the characteristic 'whoop' noise.

The disease is also sometimes called the '100-day cough' as it can last for 612 weeks.

It is most serious in babies under six months as it can cause breathing difficulties, dehydration, pneumonia and seizures.

It is generally less severe in older children and adults.

What are the symptoms?

Typically, the first signs of whooping cough are similar to a cold, such as a runny nose and sore throat, though a high temperature is uncommon.

After about a week, coughing bouts will start that last for a few minutes and are worse at night.

Many infants and younger children with whooping cough have the coughing fits and accompanying whoop, but not all do.

And sometimes babies don't cough or whoop as older kids do but may show signs of difficulties breathing.

The infection is generally milder in teenagers and adults than in babies and children, especially those who have been vaccinated.

How does it spread?

Whooping cough is very contagious and can be spread through tiny drops of fluid from an infected person's nose or mouth.

It can be spread when an infected person sneezes, coughs, or laughs. Others can catch it by inhaling the drops or getting the bacteria on their hands and then touching their mouths or noses.

Symptoms usually appear about 7 to 10 days after exposure symptoms can appear up to 21 days after a person is infected.

People are most contagious at the earliest stages and for up to about two weeks after the cough begins.

Why are cases rising?

More than 2,700 whooping cough cases have been reported across the country so far in 2024, with 1,319 cases reported in March alone, according to the UKHSA.

This compares to 858 cases throughout the entirety of 2023.

Cases of whooping cough peak every four or so years but the pandemic saw a dramatic fall in the incidence of whooping cough and other respiratory infections as a result of reduced mixing of people.

Professor Andrew Preston from the University of Baths Milner Centre for Evolution, said cases have been rising since the end of restrictions and a peak year had been expected to arise soon.

Vaccination rates in infants have declined compared to pre-pandemic levels, down from over 96 per cent coverage to just under 93 per cent last year.

Likewise, uptake of the maternal booster dropped from a high of 70 per cent to under 60 per cent.

This has left many more young babies and infants susceptible to infection.

Who can get the jab?

The vaccine is routinely offered three times including to women in pregnancy as it can protect the baby during the first few weeks of life.

Doctors suggest the best time to have it is soon after the 16th week of pregnancy.

The 6-in-1 vaccine is then offered to babies at 8, 12 and 16 weeks of age and a booster at 3 years and 4 months.

Older children and adults arent routinely vaccinated, except during pregnancy or a whooping cough outbreak.

My child is vaccinated, can they still get whooping cough?

Yes. Vaccines are never 100 per cent effective but do offer the best defence against the disease.

As with Covid jabs, even if they do not stop your child getting the illness, the likelihood is that it will be less severe.

As well as reducing overall severity, people who are vaccinated are likely to suffer from the cough for a shorter period.

Is whooping cough treatable?

Yes, although treatment depends on age and how long it has been since catching the infection.

Children under 6 months who are very ill and people with severe symptoms will usually be admitted to hospital for treatment.

People diagnosed during the first 3 weeks of infection may be prescribed antibiotics to take at home.

These will help stop the infection spreading to others but may not reduce the symptoms.

Those who have had whooping cough for more than 3 weeks will not normally need treatment as they are no longer contagious and antibiotics are unlikely to help.

Rest, drinking plenty of fluids and painkillers such as paracetamol or ibuprofen, should be taken for a fever.

Cough medicines are unlikely to be effective and are often not suitable for young children so should be avoided.

What should I do if Im worried my child has it?

First, call your GP or NHS 111 and explain the symptoms.

They may then arrange for you or your child to come in for tests and treatment.

If you or your child are taking antibiotics for whooping cough, you need to be careful not to spread the infection to others.

The NHS recommends those infected stay away from nursery, school or work until 2 days after the start of antibiotic treatment or, if not taking antibiotics 3 weeks from when the coughing bouts started.

Childrens mouths and nose should be covered with a tissue when coughing or sneezing and these should be disposed of immediately.

Hands should be washed regularly with soap and water.

My child isnt vaccinated. Am I too late?

No. It is best to have vaccines on time, but they can still have whooping cough as part of the 6-in-1 vaccine up to the age of 10.

Babies are given 3 doses of the 6-in-1 vaccine as part of the NHS vaccination schedule at 8, 12 and 16 weeks.

They are also offered a 4-in-1 pre-school booster, aged 3 years 4 months If your child has missed their 6-in-1 vaccinations, contact their GP surgery.

Original post:

School chaos fears as kids suspected of having whooping cough should be excluded for up to 3 weeks amid 'worst - Daily Mail

AstraZeneca has started to pull its Covid-19 vaccine from global markets because of low demand, the pharmaceutical giant said. The decision closes the chapter on a shot that was widely used in the early stages of vaccination drives in many parts of the world before being supplanted by rivals that were better suited to take on an evolving virus.

The move was not related to any concerns about the shots side effects, the company said.

Since the vaccine was approved in Britain in December 2020, over three billion doses have been supplied globally. But in the past few years, demand has plummeted as other manufacturers have released shots tailored to newer variants and countries have opted to use those. AstraZenecas shot, which was developed with Oxford University, is no longer being manufactured or supplied.

The company said it had decided to voluntarily withdraw all licenses to market its Covid vaccine. That process began months ago, and very few active licenses remain, the company said. The Telegraph in Britain earlier reported the decision on Tuesday.

In March, AstraZeneca requested that the vaccine be withdrawn from most European countries. The European Commission approved the move, which went into effect this week.

Sheena Cruickshank, an immunologist at the University of Manchester, said the companys decision to pull the shot was not a surprise. Unlike other manufacturers, AstraZeneca did not update its shot to target emerging virus variants because it used a vaccine technology, known as a viral vector, that was less amenable to such changes.

There was just a recognition that it wasnt going to be a vaccine that could continue to evolve for what we need now, and that it wasnt really useful now because the SARS-CoV-2 virus has changed too much, Dr. Cruickshank said.

In clinical trials, AstraZenecas shot did not perform as well in preventing Covid as Pfizers and Modernas shots did in their own studies, but AstraZenecas still proved highly effective in preventing serious illness and death from the virus.

Concerns about a link between AstraZenecas shot and an extremely rare but serious blood clotting disorder contributed to less demand for the vaccine. Its product information was updated in April 2021 to include risks about the potential side effect. AstraZenecas vaccine was cheaper and easier to transport and store than its competitors. It became the predominant vaccine used in developing countries for much of 2021, when shots from Pfizer and Moderna were mostly going to wealthy nations.

Kim Blomley, an AstraZeneca spokesman, said the company was incredibly proud of the vaccines role in ending the coronavirus pandemic.

The vaccine was distributed in more than 170 countries, and most of its doses were administered in 2021. It was never administered in the United States outside clinical trials.

Excerpt from:

AstraZeneca Withdraws Covid Vaccine Worldwide, Citing Low Demand - The New York Times

Amid the safety concerns over AstraZeneca's Covid vaccine Covishield and Vaxzevria, the pharmaceutical giant on Tuesday said it has initiated to withdraw its Vaxzevria vaccine globally, The Telegraph reported. The company, however, said the move is due to a surplus of available updated vaccines since the Covid-19 pandemic, adding that this has led to the decline in demand for the vaccine.

The Telegraph report added that AstraZeneca's application to withdraw the Vaxzervria vaccine was made on March 5 and came into effect on May 7.

Meanwhile, on Tuesday, the company also withdrew marketing authorisation for the vaccine within Europe, reported Reuters.

AstraZeneca's latest move comes days after the Anglo-Swedish drugmaker admitted in a legal document submitted that its Covid vaccines, in very rare cases, can cause Thrombosis Thrombocytopenia Syndrome (TTS) - a rare syndrome characterized by blood clots (thrombosis) and low platelet counts (thrombocytopenia).

However, it also noted that the syndrome can be detected, even if there is no vaccination, adding that expert testimony will be required to determine causation in every case.

Despite this, the company maintained that extensive clinical trial data and real-world evidence consistently support the vaccine's safety and efficacy. It also reaffirmed that the company's first priority is patient safety.

Our sympathy goes out to anyone who has lost loved ones or reported health problems. Patient safety is our highest priority, and regulatory authorities have clear and stringent standards to ensure the safe use of all medicines, including vaccines, a spokesperson for AstraZeneca said in a statement last week.

The pharmaceutical company has been fighting a class action lawsuit against its Covid-19 vaccines, allegedly leading to several deaths across the world. It first began after a man, identified as Jamie Scott, filed a complaint against AstraZeneca, saying that he developed a blood clot and bleed on his brain, which left him with a severe brain impairment after injecting the vaccine.

Additionally, over 50 cases have been filed in the court against AstraZeneca over its vaccine effects.

The Telegraph earlier reported that AstraZeneca has admitted in court papers that its Covid vaccine, Covishield, can cause rare side effect. Covishield was developed by AstraZeneca and was produced by the Serum Institute of India.

The Supreme Court will soon hear a petition on the rare side effects associated with Covishield. While a hearing date has not yet been set, Chief Justice of India DY Chandrachud has acknowledged the petition demanding an expert panel to investigate the vaccine's side effects.

(With inputs from Reuters)

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AstraZeneca to withdraw Covid vaccine worldwide amid safety issues: Report - Hindustan Times

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AstraZeneca to withdraw Covid-19 vaccine Vaxzevria globally on weak demand - Business Standard

Patient characteristics and safety

A total of 23 patients with resection-eligible WHO grade III or IV glioma were enrolled and randomized between September 2010 and August 2014. All patients received ATL-DC vaccination as an initial series of 3 biweekly bilateral upper extremity injections of 2.5x10e6 ATL-DCs followed by up to 7 booster injections at 4-month intervals. Randomization allocated nine into the adjuvant TLR-7/8 agonist (resiquimod, 0.2% gel, 3M, applied to ATL-DC injection site days 0, 2, 4 post-DC injection) group, nine into the adjuvant TLR-3 agonist (poly-ICLC, 20mcg/kg IM, Oncovir, upper extremity, at time of DC injection) group, and five to the adjuvant placebo arm where patients received either carrier gel without resiquimod or IM saline injection. (Fig.1A, Supplementary Fig.1). All patients were followed for clinical evaluations, toxicity, survival, imaging changes, as well as in-depth systemic immune monitoring. Baseline patient characteristics are presented and segregated by treatment group in Table1 (see also Supplementary Data1). The median age was 45.3 (range 26.272.8) years, and 57% of the enrolled patients were male. Patients were enrolled prior to the 2016 update to the WHO classification of central nervous system tumors; 65% (n=15) had histopathological diagnoses of WHO Grade IV glioblastoma (now consistent with IDH wild-type glioblastoma), while 35% (n=8) of the patients were WHO Grade III (all of which would now classify as IDH-mutant astrocytoma or oligodendroglioma). Fifty-two percent (n=12) of patients were treated following recurrence, while 48% (n=11) were treated in the newly diagnosed setting. All patients were treated following surgical resection and standard-of-care treatment. The molecular characteristics of the patient tumors are outlined in Table1. Overall, MGMT methylation was seen in 35% (n=8), IDH mutations were observed in 35% (n=8, all grade III), and EGFR amplification was seen in 44% (n=10, all glioblastoma) of patients, consistent with the heterogenous population of malignant glioma patients. There were no statistically significant differences in age, sex, Karnofsky performance status, MGMT methylation status, pre- or postsurgery enhancing tumor volume, nor steroid administration at enrollment. No statistically significant differences were observed between the molecular characteristics, although the number of patients in each treatment group was small.

A Timeline of PBMC acquisition and analysis using CyTOF and/or RNAseq. V = vaccine, D = Day. (Figure created with the help of BioRender). B Schematic of differential gene expression analysis performed on pre-treatment and post-treatment PBMCs of indicated treatment groups. Differentially expressed genes (DEGs) in TLR agonist-treated groups are compared against their changes in the placebo group to identify DEGs specific to the TLR-agonist groups. C, D Enriched gene set terms in Gene Ontology Biological Process (C) or ARCHS4 TF Coexp (D) datasets that significantly overlap with the union of DEGs from ATL-DC + poly-ICLC and ATL-DC + resiquimod groups (P values, FDR-adjusted, two-sided fisher exact test). E Differential gene expression (pre vs. post-treatment fold change, in log2) of representative antigen presentation and IFN-related genes across treatment groups (P values, two-sided Welch t test). F Gene set enrichment score differences (pre vs. post-treatment, delta GSVA score) of representative IFN-related genesets across treatment groups (P values, two-sided Welch t test). G Heatmap of single-sample, gene set enrichment scores (GSVA) of type I and type II interferon genesets in pre-treatment, ATL-DC + placebo, ATL-DC+poly-ICLC and ATL-DC+resiquimod samples. The number of sample pairs analyzed in panels E and F are: ATL-DC+placebo, 5 pairs; ATL-DC+poly-ICLC, 8 pairs; ATL-DC+resiquimod, 8 pairs. The rectangular box in each boxplot represents the interquartile range (IQR), spanning from the first quartile (25th percentile, bottom of box) to the third quartile (75th percentile top of box). Inside the box, the median (50th percentile) is marked. The whiskers (shown as lines extending from the box) extend to the largest and smallest non-outlier values within 1.5 times the IQR, while outliers lie beyond the whiskers.

Overall, the addition of a TLR agonist-induced only Grade 1-2 treatment-related adverse events (TRAEs), and all adverse events reported resolved without further treatment or hospitalization (Table2). The most common TRAEs were rash (39%), fever (35%), and fatigue (26%; see Table2), and were more common in patients treated with resiquimod and poly-ICLC. 88.9% of patients who received resiquimod reported a temporary localized, cutaneous rash that resolved without further treatment. Other observed adverse events were not uncommon in the setting of postoperative central nervous system (CNS) tumor treatment. However, no serious adverse events (Grade 3-4) attributable to the treatment were observed. As such, the addition of a TLR agonist to ATL-DC vaccination in malignant glioma patients was found to be safe and tolerable.

The primary endpoint of this clinical trial was to evaluate systemic immune response changes induced by ATL-DC vaccination with and without TLR agonist administration. As such, we collected PBMCs at baseline (pre-treatment), one day after the vaccination (on treatment), and then following the completion of the treatment cycle (post-treatment) of each patient (Fig.1A). We aimed to understand how the adjuvant administration of TLR agonists modified the immune response in comparison with ATL-DC vaccination alone (placebo control).

We first performed paired bulk RNA-seq on patient-matched, pre-treatment and post-treatment PBMC samples that passed QC (see sample list in Supplementary Data1C). For each gene, we computed the difference between its expression in the pre- and post-samples of patients in each treatment group: ATL-DC+placebo (n=5 pairs); ATL-DC+poly-ICLC (n=8 pairs); ATL-DC+resiquimod (n=8 pairs); for brevity, we refer to them as placebo, poly-ICLC and resiquimod, respectively. To identify expression changes specific to the TLR agonist groups, we identified genes whose average upregulation in the TLR agonist pairs (poly-ICLC or resiquimod) were at least two-fold higher than the placebo pairs (Fig.1B, Supplementary Data2A, see Methods).

Genes upregulated in the TLR agonist groups were involved in antigen processing and were enriched with known interferon-stimulated genes (ISGs) (Fig.1CE, Supplementary Data2B, C). This observation was also confirmed by per-sample gene set enrichment analysis, where the TLR agonist-treated groups displayed higher enrichment of both type I and II interferon downstream gene sets compared to ATL-DC/placebo (Fig.1F, Supplementary Data2D, E). PBMC samples with higher absolute enrichment scores of interferon gene sets were dominated by post-treatment samples from both grade III and IV glioma patients in the TLR-agonist-treated groups (Fig.1G). The two TLR agonist-treated groups showed a largely similar trend in treatment-induced gene expression changes, which included a measurable increase in the expression of ISGs in the peripheral blood of malignant glioma patients. However, we noted that the resiquimod group had a more heterogenous response, which resulted in a lower degree of statistical significance compared to that of the poly-ICLC group.

We performed CyTOF on PBMC timepoints with a 27-marker heavy metal antibody-conjugated panel for 20 of the 23 patients where sufficient material was available (placebo, n=4 pairs; poly-ICLC, n=9 pairs; resiquimod, n=7 pairs; see Supplementary Data1C, 3A, 3B). The panel was selected to be able to broadly characterize different immune cell types, activation/effector, memory, and exhaustion phenotypes, with a bias towards T-cell relevant markers. The different immune cell type populations were visualized by the uniform manifold approximation and projection (UMAP) method (Fig.2A), which we broadly assigned to seven different major immune populations based off the normalized heatmap marker expression (Fig.2B).

A A UMAP projection of the pre- and post-treatment PBMC sample pairs from twenty patients (placebo, n=4 pairs; poly-ICLC, n=9 pairs; resiquimod, n=7 pairs). Clustering was performed with a random sampling of 5,000 cells from each patient. B Heatmap of normalized expression of all 27 cell markers within cell populations identified in the patient PBMCs. C, D Normalized expression of indicated markers in monocyte (C), or T cell populations (D) within the PBMC samples of patients from indicated treatment groups. P values, two-sided Wilcoxon rank sum test. E, UMAP projection of the PBMC-derived single cells (n=99,590). The immune subset associated with each cluster is inferred based on the clusters differentially expressed transcripts. Canonical markers of known immune subsets are shown. F, G Heatmaps showing the union of recurrent DEGs computed between ATL-DC treated samples (combined with placebo, resiquimod or poly-ICLC) and pre-treatment samples in the myeloid populations (F) or lymphocyte populations (G). Shown in the heatmaps are the log fold change values of the DEGs in each cell population grouped by their treatment groups. The number of sample pairs analyzed in C and D are: ATL-DC+placebo, 4 pairs; ATL-DC+poly-ICLC, 9 pairs; ATL-DC+resiquimod, 7 pairs. The rectangular box in each boxplot represents the interquartile range (IQR), spanning from the first quartile (25th percentile, bottom of box) to the third quartile (75th percentile the top of box). Inside the box, the median (50th percentile) is marked. The whiskers (shown as lines extending from the box) extend to the largest and smallest non-outlier values within 1.5 times the IQR, while outliers lie beyond the whiskers.

After 3 cycles of treatment, the post-treatment samples of patients in the TLR agonist groups showed a significant increase in the proportion of proliferating Ki67+CD14+ classical monocytes (Fig.2C, Supplementary Data3C). Such findings were corroborated by the increased monocyte fraction and CD14 transcript expression after ATL-DC+TLR agonist-treated samples (Supplementary Fig.2A, B, Supplementary Data3D). ATL-DC+TLR agonist treatment induced PD-1 expression in CD4 T cell population and increased the T-cell normalized expression of PDCD1 (the transcript that encodes PD-1 protein) and TCF7 (a marker of progenitor-like T cells) (Fig.2D, Supplementary Fig.2C). Moreover, expression of markers associated with irreversible T cell exhaustion, such as CD38 and CD3933,34, were also significantly reduced after ATL-DC+TLR agonist treatment (Fig.2D, Supplementary Fig.2D). Increased expression of PD-1 and decreased expression of CD38 and CD39 suggest the addition of the TLR agonists led to enhanced systemic T cell activity and cellular fitness in the patient.

To delineate the changes induced by ATL-DC and TLR agonist treatment in discrete peripheral blood immune cell subsets, we performed single-cell RNA-seq on selected patients at baseline and then following the completion of therapy. We analyzed two representative sample pairs from each cohort (placebo, poly-ICLC, and resiquimod) (Supplementary Data1C, 3E). We identified a total of twelve clusters from the total PBMC immune cell population and annotated these clusters based on differentially expressed gene markers in each cluster. From the initial clustering, we were able to identify multiple populations of CD4+ and CD8+ T cells, two populations of NK cells, three monocytic cell populations, B cell, and dendritic cells (type 2 conventional dendritic cells (cDC2) and plasmacytoid dendritic cells (pDCs), in accordance with the previous characterization of these cell types in peripheral blood (Fig.2E and Supplementary Fig.2E, F).

Differential gene expression analysis across the different lymphoid and myeloid populations revealed concordant upregulation of known ISGs (e.g. IFI6/35/44L, ISG15/20, IFIT3, IFITM1/3, GBP1/5, MX1, STAT1, and CXCL10) and antigen presentation-related proteasomes (PSMB9 and PSME2) in both TLR agonist sample pairs. The magnitude of induction was weaker in the paired PBMC samples obtained from the resiquimod group compared to the poly-ICLC group (Fig.2F, G).

Thus, our combination of high dimensional proteomics, bulk and single-cell RNAseq demonstrates how adjuvant TLR administration in conjunction with ATL-DC reproducibly increases the proportion of canonical CD14+ monocytes within the systemic blood circulation. This TLR agonist administration was also associated with enhanced T cell activity, coupled with decreased expression of CD38 and CD39 and their downstream T cell-suppressive adenosine pathway33,34,35. ATL-DC+TLR agonist-driven induction of ISGs across lymphoid and myeloid populations identified in our scRNAseq analysis corroborated our bulk transcriptomic analysis. Given the consistent changes observed with TLR agonist administration, we examined whether these systemic measurements correlated the observed progression-free and overall-survival differences between these patient populations to speculate on their contribution.

Median follow-up of patients treated on this clinical trial was 2.2 years after surgery, although the long-term survivors have now been followed for over 10 years. Median progression-free survival (PFS) was 8.1 months; and median overall survival (OS) was 26.6 months. Although this clinical trial was not designed or powered to detect effects of these treatments on survival between the treatment groups, there were noticeable differences in median survival between the treatments groups for both OS (placebo: 7.7 months, poly-ICLC: 52.5 months, and resiquimod: 16.7 months; log-rank P=0.017) and PFS (placebo: 5.5 months, poly-ICLC: 31.4 months and resiquimod: 8.1 months; log-rank P=0.0012) (Fig.3A). Because the trial included patients with both grade III and IV tumors, we stratified our analysis based on tumor grade. When we analyzed only the grade IV (GBM) patients, we observed a trend towards improved PFS (log-rank P=0.068) and OS (P not significant) (Fig.3B). Interestingly, for the IDH mutant/Grade III cohort, all four patients that received ATL-DC + poly-ICLC treatment are still alive at the data cutoff date (three of the patients have survival > 120 months and one > 112 months), and they have significantly longer OS and PFS compared to the other (n=4) grade III patients who received ATL-DC + resiquimod or ATL-DC alone where median OS was 15.73 months (Fig.3C).

AC Progression-free survival (PFS, top) and overall survival (OS, bottom) of all patients (A), patient subset with GBM (B), or grade III glioma (C) in indicated treatment groups. P values, log-rank test. D, E, Multivariate Cox proportional hazards analysis assessing the hazard ratios of tumor progression in TLR agonist treatment groups against placebo in all patients (D) or GBM subset (E) after adjusting for other clinical covariates (Tx_Group=treatment group, RecurNum=number of recurrences prior to ATL-DC treatment). In the forest plot, the squares are the hazard ratio (HR) estimates, the error bars are 95% confidence interval (CI) of the HR, the P value of each covariate is based on its Wald statistics, the P values are not adjusted. In D, the sample distribution in each covariate is Tx_Group: placebo=5, poly-ICLC=9, resiquimod=9; Grade: III=8, IV=15; MGMT_methylation: True=8, False=15. In E, Tx_Group: placebo=4, poly-ICLC=5, resiquimod=6. F, MR-computed volumes of post-treatment, recurrent tumors in indicated treatment groups. Treatment groups: Placebo (n=5), Resiquimod (n=8); Poly ICLC (n=9). P values, unpaired, two-sided Wilcoxon rank sum test.

We performed multivariate Cox proportional hazard (PH) analysis, adjusting for clinical variables that are significantly correlated with OS or PFS as a single variable (tumor grade, MGMT methylation status, and number of recurrences). Our analysis confirmed that patients in the poly-ICLC and resiquimod treatment groups had a lower risk of progression that was independent of grade, MGMT methylation, and number of recurrences (Fig.3D). Risk of death was significantly lower in the poly-ICLC group, while the resiquimod group showed a similar trend that was not statistically significant (Supplementary Fig.3A). In the GBM patient subset, TLR agonist treatment also significantly lowered risk of recurrence, but not risk of death (Fig.3E, Supplementary Fig.3B).

To determine whether this treatment directly impacted tumor volume, MR imaging was performed, and contrast-enhancing tumor volume was quantified over time. We noted that the rate of tumor volume increase over time in the ATL-DC/placebo treatment cohort was higher than in the ATL-DC/resiquimod treatment (p=0.022) and the ATL-DC/poly-ICLC treatment groups (P<0.001; Fig.3F). Anecdotally, we observed an increased T2/FLAIR MRI signal after completion of the vaccine series in two of the four long-term survivors who received ATL-DC/poly-ICLC (Supplementary Fig.3C, D), although such findings are potentially confounded by prior radiation therapy, and thus we cannot ascribe such changes solely to the vaccine/TLR agonist intervention. However, this increased post-vaccination T2/FLAIR on MRI was not seen in patients who did not receive poly-ICLC (not shown).

Finally, we asked if the magnitude of interferon pathway induction by the adjuvant TLR agonist treatment directly correlated with OS or PFS. This could allow for the use of an interferon activity score as a biomarker for productive anti-tumor immune responses following ATL-DC immunotherapy. To this end, we stratified the patients by the median GSVA score of the HALLMARK INTERFERON GAMMA RESPONSE gene set in post-treatment PBMC samples. We confirmed that patients whose post-treatment samples displayed higher interferon gene set scores (median) had longer OS and PFS than those with lower scores (Fig.4A, Supplementary Fig.4A). Separate analyses on the grade IV (GBM) and grade III glioma patients showed a concordant trend but with a lower degree of statistical significance; this was likely caused by the small sample sizes. Notably, multivariate Cox PH analysis strongly suggested that the interferon gene set score is a significant predictor of tumor recurrence (Fig.4B, C) and death (Supplementary Fig.4B), even after adjusting for other potentially confounding clinical variables. To ensure that the correlation is not specific to this single gene set, we confirmed that the gene set scores of other interferon gene sets after ATL-DC treatment are also positively correlated with the patients OS and PFS (Supplementary Data4A, B). Such findings can be confirmed in larger subsequent studies.

A Kaplan-Meier progression-free survival curves of all patients (left), GBM (center), and Grade III glioma subsets (right) stratified by their HALLMARK_INTERFERON_GAMMA_RESPONSE GSVA scores in their post-treatment PBMCs. P values, log-rank test. B, C Multivariate Cox proportional hazards analysis assessing hazard ratios of tumor progression in patients with high HALLMARK_INTERFERON_GAMMA_RESPONSE GSVA score in all patients (B) or GBM subset (C) after adjusting for other clinical covariates. In the forest plot, the squares are the hazard ratio (HR) estimates, the error bars are 95% confidence interval (CI) of the HR, the P value of each covariate is based on its Wald statistics, the P values are not adjusted. In B, the sample distribution in each covariate is GSVA score (post-Tx):

Taken together, these data suggest that the addition of TLR agonists to ATL-DC vaccination shifts towards an interferon-induced immune response in both lymphoid and myeloid cells. Poly-ICLC and resiquimod appear to upregulate similar ISGs but with different magnitude. Enhancing systemic ISG-signaling may reflect an environment more favorable towards the generation of an antitumor immune response and clinical effects.

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TLR agonists polarize interferon responses in conjunction with dendritic cell vaccination in malignant glioma: a ... - Nature.com

More than one in nine eligible children nationally did not receive any dose of the measles vaccine in the 2019-21 period and nearly 30% received just one dose. This worrying fact came to light after frequent outbreaks of measles post-Covid prompted researchers from the health ministry's immunization division, Banaras Hindu University and the Bill and Melinda Gates Foundation to take a closer look at vaccination data from the National Family Health Survey (NFHS-5). In some districts in Uttar Pradesh, with high number of births, prevalence of zero-dose children was as high as 34.2% in Prayagraj and 32.2% in Hapur. In almost all northeastern states, zero-dose prevalence was roughly 25%. In a paper published in the journal Vaccine, the researchers investigated dose-wise measles vaccination coverage and explored gaps in immunization focusing on zero-dose, one-dose, and two-dose coverage among children aged 24-35 months. The study analysed information from 43,864 children taking into account socio-demographic variables such as birth order, wealth quintile, gender, social group, religion, residence, mother education, delivery-related factors, and media exposure. The study noted that a significant percentage of children receiving zero doses signalled a concerning gap in immunization coverage. The analysis showed considerable variations between states and districts in zero-dose prevalence. Even within a state, there were significant differences at the district level. For instance, in Arunachal Pradesh, West Siang district had the highest prevalence of children classified as zero-dose cases, 49.6%, while Lower Dibang Valley district had 2.8%. Another major cluster region was in UP where Prayagraj and Banda districts had 34.2% and 32.2% respectively, while in Hapur and Etawah 2.6% and 2.1% were zero-dose children. The analysis found children with higher birth orders and those from the poorest wealth quintile exhibited a higher percentage of zero doses. Mothers with lower levels of education showed increased odds of having zero-dose measles children. Additionally, mothers with limited media exposure demonstrated a higher probability of their children having a zero-dose status for measles. "Measles outbreak is considered an early warning sign for immunization programmes and can be effectively used as a signal for tracing missed and dropout children and overall systems strengthening. It is an ideal tracer as measles outbreaks visibly signal clusters with suboptimal immunization service delivery and can drive prioritisation of targeted interventions to improve programme performance and advocacy," stated the paper. Measles outbreaks were reported in 2022 from several districts of Maharashtra, Bihar, Gujarat, Haryana, Jharkhand, Kerala and Delhi, and measles-related deaths were also recorded subsequently. With humans being the only reservoir for the measles virus and no documented evidence of asymptomatic carriers, it is believed it can be eliminated. In 2017, India adopted the 'National Strategic Plan for Achieving and Sustaining Measles and Rubella Elimination'. In Sept 2022, India adopted a roadmap for eliminating measles and rubella. There is an urgency to reach at least 95% coverage for both doses of measles vaccine as unvaccinated (zero-dose) children "pose an immediate health risk, amplify disease transmission, and act as a barrier to the measles elimination goal". "With consistent efforts, the country aims to catch up on the immunization gaps and vaccinate dropped-out and left-out children this year through Intensified Mission Indradhanush (IMI) 5.0 campaigns. So far six phases of Intensified Mission Indradhanush (IMI) have been conducted from 2017 to 2022 with a focus on measles rubella (MR) elimination vaccinating approximately 1.9 million children," stated the paper.

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Spurt in post-Covid measles cases reveals big gaps in vaccination - The Times of India

Lets get this in perspective. The AstraZeneca (AZ) Covid vaccine is being withdrawn worldwide after the pharmaceutical company admitted in a British court that it can, in rare cases, cause fatal blood clots.

More than 50 families are currently taking legal steps for compensation, claiming the jab was defective and caused long-term injury or death to their loved ones.

Sadly, given that the Covid vaccine campaign was by far the biggest in world history and that it had to be done at unprecedented speed such isolated tragedies were, Im afraid, inevitable.

The question is whether, on a population-wide basis, the benefit of the vaccines outweighed the risks and on that score, the evidence is overwhelming.

Yes, the Governments medical advisers were overly optimistic when they speculated during the pandemic that, if the whole population could be vaccinated, our collective immunity could be raised to the point that the virus itself was eradicated. This has never happened, as ongoing Covid waves still prove.

More than 50 families are currently taking legal steps for compensation, claiming the jab was defective and caused long-term injury or death to their loved ones

But we must never lose sight of the full picture. More than three billion AZ doses were given worldwide, and an estimated 6.5 million lives were saved.

And in all probability, I am one of them.

In November last year, aged 85, I caught the virus for the first time and spent five days in hospital, weak, exhausted and constantly breathless.

F or two days, I was on oxygen. The part of my brain that has been obsessed with medicine all my life found this experience rather interesting. Im not sure that my family viewed it in quite the same light.

I owe my survival, I believe, to the fact that I had the AZ vaccine early in 2021, followed by three boosters. In my case, some of the batches came from Pfizer as well as AZ, but all the data shows they were approximately equal when it came to reducing the severity of the disease.

Multiply my own case by many millions and its obvious that mass vaccination not only enabled legions of patients aged 60 and over to withstand the worst of the disease it also kept our hospitals from being overwhelmed and collapsing into chaos.

Conspiracy theorists have seized on AZs recent court admission, claiming it proves the drug companies pushed dangerous and ineffective vaccines on the world.

But in the event, only a few people comparatively speaking were so unlucky as to suffer from blood clots or other serious complications.

Why these clots occurred in a very small number of people, we do not yet know, but no one could have predicted them.

And so Im sorry to disappoint the conspiracy theorists, but there was nothing opportunistic about these jabs or the way they were produced.

It is worth recapping here how the AZ vaccine worked. The Oxford University scientists behind it produced a genetically engineered form of Covid-19, which could not cause illness but which did help patients to produce their own protective immune response.

One theory is that the damage suffered by some people was caused by a specific component of the vaccine: an adenovirus, which was used as a sort of carrier to kickstart an immune reaction in the patient. The danger was missed in trials, however, because this adverse reaction was so exceptionally rare.

For the people affected, it is a tragedy but it is no reason to dismiss the vaccines out of hand.

Why, today, do so many people remain doubtful about the Covid jabs and unwilling to see them as the modern miracle they really are?

In part, this is down to the mood of terror as the pandemic first took hold.

As pictures hit the news of Italian intensive care units in crisis at the beginning of March 2020, panic spread even faster than Covid itself. Conflicting opinions on the best course of action became dizzying and deafening: some urged draconian lockdowns, others pleaded for the use of face masks and hand-washing, still others insisted the risks were being exaggerated.

Professor Hugh Pennington: I owe my survival, I believe, to the fact that I had the AZ vaccine early in 2021, followed by three boosters

The country became a hotbed for competing conspiracy theories, fuelled by social media some of which were malicious and generated by troll farms in hostile nations.

(Such lurid claims continue even now, of course, with anti-vaxxers blaming every medical condition, from the collapse of footballers on the pitch to the Princess of Waless cancer diagnosis, on the vaccine.)

Cast your mind back to those dark and confused days, and remember how loud were the calls from politicians and NHS staff for any means of preventing the spread of Covid, since a cure seemed out of reach as it still does.

Yet heres the thing. Even though the AZ vaccine was hailed as an innovation when it was first approved for use in the UK at the end of December 2020, it was actually the culmination of many years work.

Much of the technology was, in fact, waiting to be used when Covid-19 first emerged in 2020. The AZ team even had a candidate vaccine ready by February that year before the British government had given serious consideration to the need for any lockdown.

S o those who claim the drug companies hurried out experimental, untested, recklessly dangerous vaccines are seriously wide of the mark.

Finally, on December 8, 2020, what then prime minister Boris Johnson memorably described as the scientific cavalry coming over the brow of the hill arrived.

Yet there were widespread misunderstandings about how the new jabs would work. Most lay people seemed to expect the Covid vaccine to form an impenetrable barrier against disease. Thats how we tend to view jabs against everything from TB to measles, polio to smallpox.

The reality, in the case of the Covid vaccines, is different. They are more of a superpower, making our bodies stronger and better able to fight off an enemy . . . like Popeye when he eats spinach.

And like Popeye, we dont stay superhuman for ever. The power wears off and needs to be renewed from time to time. Yet even if they werent a magic shield, the vaccines proved to be essential.

Though they had limited success in stopping the virus from multiplying in the mouth, nose and throat, they were highly effective at minimising the risk of serious Covid infection in the rest of the body, such as the lungs and vital organs. This saved countless lives.

What they also did less well, as we eventually found out, was stopping the spread of the disease through the air from our mouths and noses. Of course, none of this was clear amid the panic of the pandemic and even today, we find ourselves searching for answers. The debate continues about how much good and how much harm was done by lockdown, for example.

So yes, many questions remain. It is now clear that, for a tiny minority of people, the decision to be jabbed proved disastrous.

But we should remember that bigger picture, too. Without the jabs, Britains older population would have been decimated.

Even with the introduction of the vaccines, Britain lost up to 230,000 people to the virus. Without the jabs, many thousands more would have died.

And I am probably one of them.

Hugh Pennington is an emeritus professor of bacteriology at the University of Aberdeen.

PAT HAGAN: Was it rushed out? How many died from it in the UK? And could you still suffer from side-effects?

The jab was the first in a series of vaccinations to offer a glimmer of hope that we might be able to tackle the virus

The AstraZeneca jab is said to have saved more than 6.5million lives globally in the first year of use alone.

But yesterday, the manufacturer revealed its pulling the plug on its game-changing Covid-19 vaccine, after 50million doses were given in the UK.

Unveiled in January 2021, ten months after the World Health Organisation declared Covid-19 a global emergency, the jab was the first in a series of vaccinations to offer a glimmer of hope that we might be able to tackle the virus.

It was hailed as one of the great scientific achievements of the modern era, slashing the time it normally takes to get a new vaccine on the market from almost a decade to just months.

And in February 2022, Professor Sarah Gilbert, a vaccine specialist at Oxford University and one of the pioneers behind the AstraZeneca (AZ) jab, was made a Dame in recognition of this work.

But the vaccine remains controversial.

The manufacturer is being sued by more than 50 alleged victims and grieving relatives in a multi-million-pound High Court action.

In one case its claimed a 35-year-old mother-of-two, Alpa Tailor, died from adverse side-effects after the jab; another claimant, Jamie Scott, a father-of-two, says hes been left with a permanent brain injury.

So whats the truth about the jab and why is it being scrapped?

Its no longer any use. In an official announcement earlier this week, Cambridge-based AstraZeneca said it was shutting down production due to a surplus of available updated vaccines which target new variants of the virus.

Basically, that means the virus has evolved so much from its early strains that the AZ jab is much less effective than the dozens of more up-to-date ones developed by other drug companies.

The vaccine has had its time, says Peter Openshaw, professor of experimental medicine at Imperial College London. But it was really fundamental in terms of pushing forward the vaccine agenda. Theres no doubt at all that it saved millions of lives.

It is true to say that, fairly early on in the pandemic, several countries suspended the use of the AZ vaccine after reports that some patients had subsequently developed life-threatening blood clots particularly in the brain.

These countries included Denmark, Norway, Iceland, Austria and Italy. Germany banned it in the under-60s.

And in April 2021, the Medicines and Healthcare Products Regulatory Agency (MHRA) admitted there was a possible link between the jab and rare blood clots, known as thrombosis with thrombocytopenia syndrome, which raises the risk of a stroke.

A later analysis at Oxford University suggested that for every 10 million people given the jab, roughly 66 would get a clot in their veins.

In contrast, Covid caused an average of 12,614 clots in veins. Even taking the contraceptive pill was a bigger risk than the jab.

Shortly afterwards, it was announced that those under 30 in the UK would be offered alternative jabs.

Last month, AstraZeneca admitted for the first time that the jab could cause clotting problems in very rare cases.

Professor Adam Finn, an infectious disease specialist at Bristol University, told the Today programme on Radio 4: Its very clear that this vaccine was associated with clotting thats been clear for a long time but only recently acknowledged [by AstraZeneca].

But he insisted this rare side-effect was not relevant to the withdrawal of the AZ vaccine.

One of the breathtaking features of the AZ vaccine story was the pace at which it was developed.

The speed with which it was developed was phenomenal, says Professor Openshaw.

This aroused concerns among some sections of the public that the vaccine had been rushed and lacked appropriate safety checks. But experts are adamant no corners were cut.

Furthermore, very rare side-effects, such as the vaccine-related clots, wont always show up in drug trials where only a few hundred, or a few thousand people, are involved.

They often only come to light when millions more people are given them.

Professor Openshaw says: We have to be honest and say everything we take in terms of medicine carries a risk, however small, but this has to be balanced against the enormous good they can do.

Clinical trials suggested the AZ vaccine was roughly 72 per cent effective at preventing symptomatic Covid-19 infections when patients were given two doses spaced four to 12 weeks apart.

But the UK switched to using mRNA vaccines, made by Pfizer and Moderna, as these were found to be more effective (the Pfizer vaccine was 97 per cent effective against symptomatic Covid).

Figures from the MHRA show 81 deaths in the UK are possibly linked with adverse blood-clotting reactions to the AZ vaccine. That doesnt mean the jab has been confirmed as the cause of death.

The 51 victims and relatives of alleged victims are claiming damages worth up 100million.

They argue that the risk of life-threatening clots means the vaccine was not as safe as individuals were entitled to expect.

They also believe the Government vaccine damage scheme is flawed. It only makes a payout if it can be proved someone died from the vaccine or was left severely disabled.

Professor Finn says: Anyone who has received the vaccine in the past without any problems is not at risk of any side-effects now.

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Professor Hugh Pennington admits: I owe my life to AstraZeneca jab - Daily Mail

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European countries have reported a surge in whooping coughc ases in first quarter of 2024, with 10 times as many identified as in each of the previous two years.

Nearly 60,000 cases were reported by European Union and European Economic Area countries over the period, the European Centre for Disease Prevention and Control said on Wednesday, with 11 deaths in infants and eight among older adults.

In the UK cases of whooping cough could reach a 40-year high in 2024, experts have warned amid a rapid rise in cases.

Whooping cough, or pertussis, is a bacterial infection of the lungs and airways, and is endemic in Europe. It can be very dangerous for young babies or older people.

Bigger whooping cough epidemics are expected every 3-5 years even in countries with high vaccination rates, the ECDC said, although a slight dip in immunisation during the COVID-19 pandemic may have been a factor in the rise. Circulation of whooping cough was also very low during the pandemic and its related restrictions on movement, making the rise seem larger.

After about a week, you or your child:

The cough may last for several weeks or months.

The numbers are still historically high, though. In the first three months of 2024, there have already been as many cases as there were in an average year between 2012 and 2019.

The agency noted that much of the population had missed out on natural boosting of their immunity to whooping cough because they had not been exposed to it during the pandemic.

Babies under six months are at particular risk from the infection.

Its essential to remember the lives at stake, especially our little ones. Vaccines against pertussis have proven to be safe and effective, said ECDC Director Andrea Ammon.

Most European countries routinely immunise children against pertussis and many also vaccinate pregnant women to protect their babies.

The ECDC said some countries may want to consider giving boosters to older children and adults too, as immunity can wane.

Paul Hunter, professor in medicine at the University of East Anglia (UEA), said: For most adults the whooping cough is not life threatening, though can be very unpleasant.

This is a chronic repeated bout of coughing which can be so bad that people feel it a struggle to breathe in again.

It used to be much more common in the last century up until the vaccine was introduced.

However, this current year looks like we may see more cases than we have seen in any of the last 40 years.

Prof Hunter said that a number of factors could be behind the rise in cases, including: a drop in vaccine uptake; reduced population immunity due to a fall in cases linked to social distancing measures during the pandemic; and a scare over vaccines in the early 2000s which led to a group of people aged around 21 who did not complete their vaccination.

He added: The infection can affect anyone who is not vaccinated and even some that are.

However, the main risk of death or severe long-term complications is seen in young children, especially those under three months old.

It is this age group that are most at risk of death and developing longer-term problems such as brain damage.

The problem is that this age group is too young for the vaccine in most circumstances.

That is why we offer vaccine to pregnant women. Not to protect them but to protect their babies during the riskiest first months of life.

Vaccine uptake in pregnant women has been falling quite markedly in recent years.

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Doctors warn of deadly whooping cough epidemic sweeping Europe - The Independent