Category: Vaccine

Polio

After no reported cases of wild polio for 19 weeks, vaccination efforts boosted at last endemic spots in Pakistan and Afghanistan

Sat 16 Mar 2024 09.00 EDT

The world is tantalisingly close to eradicating polio with no confirmed cases of wild polio anywhere so far this year. But experts warn that vaccination efforts and funding must not falter if the world is to rid itself of a human infectious disease for the second time in history, after smallpox.

There have been no reported cases of wild polio infection in people for the last 19 weeks. Figures from the World Health Organization reveal that the last confirmed cases were on the borders of Pakistan and Afghanistan in October and September 2023 respectively; these are the last nations on Earth where polio is endemic.

To have gone 19 straight weeks is a long period to go without a single case, thats why there is some hope [of eradication], Gordon McInally, president of Rotary International, a founding partner in the Global Polio Eradication Initiative (GPEI), told the Observer. All of us who are involved in this, every week we get an email giving us the updated figures and every week when I click open that email my heart rate goes up until I see the number in the hope that it will be zero and not one, or worse. But we take it week by week.

But those involved in eradication efforts are taking nothing for granted. The programme has come under fire before for its almost-there narrative, as described in a report last September by the Independent Monitoring Board, led by Liam Donaldson, a former chief medical officer for England.

Still, said McInally, if they can get through another 33 weeks (one full year after the last case), they will be celebrating cautiously, and if the world stays two years disease-free they can officially declare the global eradication of polio.

While the absence of confirmed cases is really encouraging, Aidan OLeary, director for polio eradication at the WHO, said: Its important we dont call the figures great. The campaign needs to be aggressive in closing any immunisation gaps, he added.

The latest WHO figures do reveal 34 samples of wild poliovirus detected from environmental and other sources in the first three months of this year, including from surveillance samples of sewage (where shed virus may circulate). We are identifying environmental isolates which does indicate theres some transmission, said OLeary, adding this needs to be zero too.

OLeary, McInally and other stakeholders met Andrew Mitchell, the minister for development, and his team on Wednesday to update them on polio, and ask the UK government to continue with its funding, which ends this year. They are asking the Foreign, Commonwealth and Development Office for 100m for the next two years. GPEIs goal is to eradicate polio by 2026.

The UK government has been the second biggest contributing government after the US towards eradicating polio, said McInally. He said funding is crucial because were at that challenging point in time where because of the geography, the nomadic nature of many of the people were trying to reach, its not easy to reach everybody to get it finished, and there is a realisation that unless we finish it completely we run the risk of it bubbling up again.

If they fail to eradicate polio in Afghanistan and Pakistan, WHO modelling suggests there could be a global resurgence resulting in some 200,000 new cases of polio each year within 10 years. Until this is done, McInally said, polio is only a plane-ride away. Imported polioviruses caused alarm in 2022 when an unvaccinated adult in New York was paralysed by the disease, and poliovirus was detected in sewage in London.

But McInally is hopeful, in part because of the programmes success in India 27 March will mark the countrys 10-year anniversary since it became officially polio-free. There are some parallelswith rural India which give him hope. Many people said you will never get rid of polio from Indiaand it was done.

Immunisations have been stepped up in Afghanistan and Pakistan; with the programme extending its target age for immunising children from under five to under 10, said OLeary, and synchronising on both sides of the border.

Another crucial challenge is vaccine-derived poliovirus transmission. This derives from the oral polio vaccine, still used in some regions, which harnesses live but weakened poliovirus.

This would not cause issues of itself, but if immunisation rates are low in a population, the vaccine strain can circulate and genetically change over time, and in rare cases cause paralysis like wild polio.

Any case is a worry, said McInally. But once we can eliminate wild virus then the vaccine-derived cases will clear up relatively quickly.

OLeary notes that there were 1,000 cases of polio a day in 125 countries in 1988 when the GPEI started. He likens the polio programme to running a marathon with a few hundred metres to go. Nonetheless he remained cautious: Eradication is a zero-sum game. We have to be very clear-eyed when we look back and everything is zero, then we can say its great.

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Global eradication of polio tantalisingly close with UK urged to keep up funding - The Guardian

Donald Trump set off a panic in some of the more extreme corners of his base last week during President Bidens State of the Union.

Trumps offense? Taking credit for the coronavirus vaccines that Biden hailed.

Alex Jones threatened to go on the warpath if Trump kept it up. Michael Flynn agreed with Joness plea for Trump to stop. And Charlie Kirk chimed in among his fellow right-wing influencers with a warning of electoral peril for Trump.

The reason for that supposed peril is the independent candidacy of perhaps the countrys most prominent vaccine critic, Robert F. Kennedy Jr. Kennedy hasnt played up his dubious and false vaccine views too much in his campaign, but he attacked Trump for his comment. Then news broke Tuesday that Kennedy has considered prominent vaccine critic and NFL quarterback Aaron Rodgers for his running mate.

All of which raises a question that has lurked beneath the surface of this campaign: Could Trumps role in forging the coronavirus vaccines and his frequent praise for them send portions of his partys growing anti-vaccine contingent into Kennedys camp?

Kennedy currently polls in the double digits. But despite being much more popular among Republicans than Democrats, he pulls about evenly from the two partys bases. At this point, theories about how Kennedys switch from the Democratic primary to an independent run might hurt Trump (raises hand) havent been borne out.

But that doesnt mean Republicans havent been concerned about it. And the concern now seems to be peaking among some Trump allies.

Do not give RFK any reason to trim at our base, to give people a little uncertainty, Kirk cautioned Trump, adding that I would stay away from the vaccine issue.

Trump has treated the issue gently in recent years. He often criticizes vaccine mandates, but hes been understandably reluctant to glom on to conspiracy theories about the safety of vaccines that he helped fast-track. And hes on the record plenty of times vouching for the vaccines and encouraging people to get them.

Florida Gov. Ron DeSantis (R) tried to outflank Trump on vaccines in the primaries, and that obviously didnt pan out. But that doesnt mean it couldnt loom in the general election for a small but significant number of base voters.

The main question is how many Republicans feel strongly enough about this issue.

The Republican base is broadly skeptical of the coronavirus vaccines and has gotten vaccinated at much lower rates than Democrats apparently contributing to many more covid deaths in Republican-leaning areas.

But not wanting the vaccines is different from being adamantly opposed to them and potentially opposing politicians who support them.

A few surveys help us drill down a little more.

A September KFF poll showed fully 39 percent of Republicans said they were not at all confident that the coronavirus vaccines were safe. And for many of them, this skepticism extended to other vaccines 19 percent for the RSV vaccine and 15 percent for flu vaccines.

Another survey around the same time showed 27 percent of Republicans said vaccines in general were at least somewhat unsafe for children.

Notably, that poll also compared Trump supporters with supporters of other GOP primary candidates. And Trump supporters were actually twice as likely to say the vaccines were unsafe (34 percent to 17 percent).

That suggests Trump has largely locked down most of his partys strongest vaccine critics. Despite his role in pushing for the vaccines, and however much hes praised the vaccines, it doesnt seem to have cost him at least, to the extent people have actually processed all of that.

But the contrast with DeSantis and other GOP candidates who dipped their toe into vaccine skepticism was somewhat muddled. DeSantis, for instance, had strongly promoted the vaccines early on.

Kennedy presents a more direct contrast, and he seems to be leaning in on this issue a bit more now. To the extent he wants to press this issue and (baselessly) pitch Trump as the father of a dangerous vaccine, it could force portions of Trumps base into a choice they havent faced before.

Maybe the anti-vaccine portion of his base will prove it truly believes in Trump and that the details are fungible, as it has on so many other issues.

But its rare you see Trump booed at his own rally, as he was when he brought up the vaccines in 2021. And last summer, Trump seemed to recognize how problematic this issue could be for him.

I really dont want to talk about it, Trump told Fox News, because, as a Republican, its not a great thing to talk about, because for some reason its just not.

That might be less of an option in a race against Kennedy.

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Analysis | Could anti-vaccine Republicans ditch Trump for Robert F. Kennedy Jr.? - The Washington Post

A Defense Department Inspector General review of the militarys COVID vaccine exemption process found that while the services largely followed policy when considering waivers, the Army and Air Force routinely overran deadlines, according to a report released Thursday.

The review also found a range of discharge types and reentry codes for service members involuntarily separated after vaccine refusal, leaving some troops with full benefits after being kicked out, while others received partial benefits.

Prolonged delays in addressing requests for religious accommodations could impact a service members job placement and impede the commands ability to make well-informed deployment and assignment choices, said Defense Department Inspector General Robert Storch said in a release.

The review began in February 2022, prompted by IG hotline calls alleging that the services were rejecting exemption requests en masse. In June that year, then-Inspector General Sean ODonnell sent Defense Secretary Lloyd Austin a memo with preliminary findings, including concerns that requests were being processed too quickly and without thorough review.

The denial memorandums we reviewed generally did not reflect an individualized analysis, demonstrating that the Senior Military Official considered the full range of facts and circumstances relevant to the particular religious accommodation request, ODonnell said.

These concerns also prompted multiple lawsuits against DoD and the services, alleging that adjudication authorities were blanketly denying religious waiver requests. One case resulted in a judge halting the Air Force from discharging anyone for vaccine refusal after a waiver denial.

In 2023, after federal legislation required Austin to repeal the mandate in January, DOD settled two of the lawsuits by paying the complainants legal fees.

In the end, the IG found that the Army and Air Force actually took longer to approve requests than their policies required.

While the Army has a 90-day deadline for processing requests, the cases reviewed averaged 192 days to receive a decision. In the Air Force, 35 reviewed requests averaged 168 days to adjudication, though the deadline was 30 days.

When Austin announced in August 2021 that the COVID-19 vaccine would become required, vaccine exemptions in the military were rare. Most were for medical or administrative reasons, like an allergy, a pregnancy or someone preparing to separate from service, rather than the highly subjective religious exemption requests that flooded the services after the mandate came down.

Policy requires that sincerely held religious beliefs be accommodated as long as they do not impact military readiness, unit cohesion, good order and discipline, or health and safety.

The IG found that decision authorities weighed expert advice while considering the health risks of allowing someone to go unvaccinated, and that in the end, each case was examined individually before making a decision.

But the unprecedented number of requests 16,000 from active duty troops as of January 2023 slowed down the adjudication process, the IG found.

At the same time, though the services followed DOD guidelines for discharges, those guidelines didnt have uniform rules for using various types of discharges and reentry codes, which govern whether someone can re-join the military again at a later date.

As a result, discharged service members experienced different impacts to their educational benefits and eligibility to reenlist in military service after discharge, according to the report, as most vaccine refusals resulted in general discharges, which specifically denies GI bill benefits.

The IG recommended reviewing the exemption process to find ways to make it more efficient during high-volume periods, as well as creating standardized policy for discharges and reentry codes after vaccine refusal.

DOD accepted both recommendations and has efforts underway to address them, according to the report.

Meghann Myers is the Pentagon bureau chief at Military Times. She covers operations, policy, personnel, leadership and other issues affecting service members.

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Services were slow to process COVID vaccine exemptions, watchdog finds - Military Times

In my mind, the spring season will always be associated with COVID-19.

In spring 2020, the federal government declared a nationwide emergency, and life drastically changed. Schools and businesses closed, and masks and social distancing were mandated across much of the nation.

In spring 2021, after the vaccine rollout, the Centers for Disease Control and Prevention said those who were fully vaccinated against COVID-19 could safely gather with others who were vaccinated without masks or social distancing.

In spring 2022, with the increased rates of vaccination across the U.S., the universal indoor mask mandate came to an end.

In spring 2023, the federal declaration of COVID-19 as a public health emergency ended.

Now, as spring 2024 fast approaches, the CDC reminds Americans that even though the public health emergency is over, the risks associated with COVID-19 are not. But those risks are higher in some groups than others. Therefore, the agency recommends that adults age 65 and older receive an additional COVID-19 vaccine, which is updated to protect against a recently dominant variant and is effective against the current dominant strain.

The shot is covered by Medicare. But do you really need yet another COVID-19 shot?

As a geriatrician who exclusively cares for people over 65 years of age, this is a question Ive been asked many times over the past few years.

In early 2024, the short answer is yes.

Compared with other age groups, older adults have the worst outcomes with a COVID-19 infection. Increased age is, simply put, a major risk factor.

In January 2024, the average death rate from COVID-19 for all ages was just under 3 in 100,000 people. But for those ages 65 to 74, it was higher about 5 for every 100,000. And for people 75 and older, the rate jumped to nearly 30 in 100,000.

Even now, four years after the start of the pandemic, people 65 years old and up are about twice as likely to die from COVID-19 than the rest of the population. People 75 years old and up are 10 times more likely to die from COVID-19.

These numbers are scary. But the No. 1 action people can take to decrease their risk is to get vaccinated and keep up to date on vaccinations to ensure top immune response. Being appropriately vaccinated is as critical in 2024 as it was in 2021 to help prevent infection, hospitalization and death from COVID-19.

The updated COVID-19 vaccine has been shown to be safe and effective, with the benefits of vaccination continuing to outweigh the potential risks of infection.

The CDC has been observing side effects on the more than 230 million Americans who are considered fully vaccinated with what it calls the most intense safety monitoring in U.S. history. Common side effects soon after receiving the vaccine include discomfort at the injection site, transient muscle or joint aches, and fever.

These symptoms can be alleviated with over-the-counter pain medicines or a cold compress to the site after receiving the vaccine. Side effects are less likely if you are well hydrated when you get your vaccine.

Repeat infections carry increased risk, not just from the infection itself, but also for developing long COVID as well as other illnesses. Recent evidence shows that even mild to moderate COVID-19 infection can negatively affect cognition, with changes similar to seven years of brain aging. But being up to date with COVID-19 immunization has a fourfold decrease in risk of developing long COVID symptoms if you do get infected.

Read more: Mounting research shows that COVID-19 leaves its mark on the brain, including with significant drops in IQ scores

Known as immunosenescence, this puts people at higher risk of infection, including severe infection, and decreased ability to maintain immune response to vaccination as they get older. The older one gets over 75, or over 65 with other medical conditions the more immunosenescence takes effect.

All this is why, if youre in this age group, even if you received your last COVID-19 vaccine in fall 2023, the spring 2024 shot is still essential to boost your immune system so it can act quickly if you are exposed to the virus.

The bottom line: If youre 65 or older, its time for another COVID-19 shot.

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COVID-19 vaccines: CDC says people ages 65 and up should get a shot this spring a geriatrician explains why it's ... - The Conversation

As rates of childhood vaccination decline and with measles on the rise again, a KFF Health Misinformation Tracking Poll, fielded in late February, examines the extent to which adults have heard and believe misinformation about the measles vaccine. The poll also examines the publics views of the U.S. government and social media companies role in moderating false health claims online.

While most of the publicincluding parentshavent heard misinformation about the measles vaccine, many are uncertain about the validity of one specific false claim. About one in five adults (18%, including 19% of parents of children under age 18) say they have heard or read the claim, Getting the measles vaccine is more dangerous than becoming infected with measles.

A relatively small share leans towards believing the claim is true. Regardless of whether they have heard the claim, a fifth of adults (19%), including one quarter of parents (25%), say the claim is definitely or probably true. Six percent of U.S. adultsincluding about one in ten (9%) parentssay they have heard the claim and think it is probably or definitely true.

Across partisans, levels of educational attainment, and race and ethnicity, fewer than five percent of adults say that the claim is definitely true, meaning that there are few ardent believers in this piece of misinformation. However, independents (37%) and Republicans (21%) are less likely than Democrats (59%) to be certain that the claim is definitely false. Those without a college degree (29%) are also less likely to say that the claim is false than those with a college degree (55%).

Large Shares Support Social Media Companies in Restricting Health Misinformation at the Expense of Certain Freedoms

Later this March, the Supreme Court will hear arguments in three important cases related to misinformation on social media that will have implications for how the U.S. government and social media companies interact with users and can moderate information.

Two-thirds (68%) of the public views the spread of health misinformation on social media as a bigger problem than censorship of speech on social media platforms (31%). This sentiment is in turn reflected in opinions about what kind of action social media companies should take to curb the spread of false health claims.

Large shares of the public support social media companies in tamping down on misinformation even at the expense of certain freedoms. About two-thirds (66%) of adults overall say, Social media companies should restrict false health information, even if it limits people from freely publishing or accessing information, while one-third instead say Peoples freedom to publish and access health information should be protected, even if it means false information can also be published.

The public is more divided about whether the U.S. government should take action. Nearly six in ten adults overall (57%) say, The U.S. government should require social media companies to take steps to restrict false health information, even if it limits people from freely publishing or accessing information, while about four in ten (42%) say Peoples freedom to publish and access health information should be protected, even if it means false information can also be published.

There are partisan divisions on both these questions, with Democrats more likely than independents or Republicans to favor both the government and social media companies taking action to restrict false health information. Notably, however, majorities of Democrats (82%), independents (57%), and Republicans (56%) say that social media companies should take steps to restrict health misinformation even if it limits certain freedoms.

The Health Misinformation Tracking Poll is part of a new KFF program area focused on identifying and monitoring health misinformation and trust in the United States, emphasizing communities that are most adversely affected by misinformation, including people of color, immigrants, and rural communities.

Designed and analyzed by public opinion researchers at KFF, the poll was conducted from February 20-28, 2024, online and by telephone among a nationally representative sample of 1,316 U.S. adults including 283 parents. Interviews were conducted in English and in Spanish. The margin of sampling error is plus or minus 3 percentage points for the full sample and 7 percentage points for the sample of parents. For results based on other subgroups, the margin of sampling error may be higher.

More here:

Most Parents Haven't Heard Misinformation About the Measles Vaccine though Significant Shares Are Uncertain About ... - KFF

Cancer treatments have continuously improved with increasing knowledge about the tumor and the immune system. Starting with surgery and radiation as effective interventions, followed by targeting rapidly diving cells with chemotherapy, researchers gradually expanded the range of cancer treatment options.

More recently, they turned to immunotherapy to target tumors more precisely. These approaches include monoclonal antibodies against tumor antigens, checkpoint inhibitors that block tumors from accessing suppressive proteins on immune cells, and chimeric antigen receptor (CAR) T cells engineered to recognize specific tumor antigens. Each of these approaches uniquely targets tumors to stop their growth or even kill the cancerous cells. However, these immunotherapeutic modalities involve targeting a singular antigen on tumors, and no therapy to date provides long-lasting immunity against possible future tumors, opening the possibility of tumor escape and re-emergence once therapy stops. Vaccines against cancer offer a potential solution to both problems.

Researchers have explored the possibility of using vaccination as a therapy against cancer since the 1990s.1 However, despite their appeal, turning the immune system into a therapy against cancer has proven to be challenging.

Cancer vaccines can either be preventative or therapeutic. Currently approved preventative cancer vaccines include the hepatitis B vaccine and human papillomavirus vaccine, both of which generate immunity against a specific virus that can cause cancer after infection. However, developing a preventative vaccine against spontaneous tumors is a much taller task.

The day before a cancer cell develops, it is a normal cell, said Christopher Schliehe, an immunologist at Erasmus University Medical Center who studies mechanisms of antigen presentation through major histocompatibility complex class I (MHC-I). You cannot vaccinate against that because its yourself.

Unlike viruses and bacteria, which have proteins and sugars that scientists can target for a vaccine, it is not currently possible to predict what mutation will occur in a cell to render a tumorigenic protein to formulate a vaccine against. Instead, researchers are interested in a model of vaccination that is used therapeutically.

T cells target cancer cells for destruction.

A therapeutic cancer vaccine introduces one or more tumor antigens to the immune system and prompts these cells to activate against the antigens, in turn, targeting and destroying the tumor. Tumor antigens come in one of two categories: tumor associated antigens (TAA) and tumor specific antigens (TSA).2 TAA are found on normal cells but at much lower densities than on cancerous cells. They can be more general targets across different patients tumors, making them ideal for a generalized vaccine goal, but because they are a self-protein, there are few T cells available to recognize these antigens. In contrast, TSA arise from mutations that alter one or more amino acids in a protein. This increases the likelihood of T cells recognizing these antigens but makes them more specific to an individuals tumor.

Studies in the 1970s that used inactivated tumor cellscombined with bacterial components, often the live vaccine bacillus Calmette Gurin, yielded conflicting results.3,4 However, this concept truly began taking form with the discoveries of dendritic cells functions in antigen presentation and stimulation of T cells, coupled with the identification of mutant antigens in tumors.5-9 Researchers incubated dendritic cells isolated from patients with either whole tumors or specific tumor peptides and then reintroduced the cells into patients.1, 10-12 These antigen presenting cells activated T cells against the tumor targets.

Its a type of immune therapy that will persist for a long time, said Eli Gilboa, a cancer immunologist at the University of Miami who studied RNA-pulsed dendritic cells as vaccine candidates.13,14 Since this therapy introduces functional antigen-pulsed dendritic cells into patients, the activated T cells also produce memory T cells analogously to immune responses against infections or preventative vaccines.15,16 This could provide long-term protection against tumor re-emergence.

However, similar to preventative vaccines against an infectious disease, the antigen chosen for a cancer vaccine is important. One of the considerations is targeting something that the tumor needs to stay a tumor, said Erika Crosby, a cancer immunologist at Duke University who studies the tumor microenvironment for developing therapeutic approaches. Whether researchers target a TAA or TSA, some of these mutated or upregulated proteins are more responsible for the cells abnormal growth and survival than others and are referred to as drivers. While a tumor may evade immune recognition by ceasing expression of certain antigens, it cannot easily stop producing its drivers, so researchers target these proteins that are more likely to be available for the immune system to recognize.17

Additionally, because therapeutic vaccines consist of antigen presenting cells that activate T cells, this becomes a dynamic therapy that can adapt to the tumor. As tumors die, they expose new antigens that dendritic cells can use to activate new T cells.18 This further reduces the likelihood of tumors evading this type of therapy by altering their antigens. An effective anticancer vaccine is not only going to allow us to put pressure on maybe a driver antigen or multiple driver antigens in tumors, but also allow us to get this epitope spreading, Crosby explained. That is going to help us keep fighting the tumor as it evolves.

Cancer vaccines offer the opportunity to use the patients own immune system in the fight against tumors.

1. Antigen preparation: Scientists can produce cancer vaccines against tumors by using the patients tumor as a source of antigen or by synthesizing peptides from tumor antigens.

2. Antigen delivery: Researchers use different vaccine platforms to deliver the antigens: patient-derived dendritic cells, adeno-associated viral vectors, and lipid nanoparticles.

3. Antigen presentation: Once administered, these antigens eventually find their way to patient dendritic cells, or are immediately expressed on dendritic cells if they are used as the vehicle. The dendritic cells travel to lymph nodes to activate antigen-specific T cells.

4. Anti-tumor immunity: Once activated, these tumor-antigen-specific T cells will multiply (a) and travel to the tumor, where they help target the tumor cells for destruction (b). Some activated T cells will become memory cells (c, shown in purple); these will reside in the lymph node or nearby tissue to protect the body against future recurrences of the same type of cancer.

Despite the promise and potential advantages of therapeutic cancer vaccines, only one, Sipuleucel-T, a dendritic cell-based vaccine, has received Food and Drug Administration approval in almost thirty years of investigation.19 The dendritic cell-based platform requires the ability to isolate, prepare, and then administer adequate numbers of antigen-pulsed cells for each individual patient, which is both labor-intensive and costly, making them less attractive to pharmaceutical companies.20,21 Although improved generation methods and the ability to outsource these efforts alleviated some of the strain, these therapies are still not as widely applicable as other immunotherapies that can be used in more patients and have shown more progress in clinical trials.22,23

While the previous decade saw the landmark approval with Sipuleucel-T, it still does not cure cancer and only extends survival by four months on average. In many other clinical trials, researchers experienced similar setbacks, where despite demonstrating safety and generating responsive cells, these formulations failed to significantly improve cancer outcomes.24

To elicit an effective immune response against cancer is particularly challenging because the cancer is expecting an immune response, Gilboa said. These overactive cells must fly under the radar of the immune system to survive, so many of these cells have developed mechanisms to evade immune defenses. The tumor microenvironment is so suppressive that you could pour T cells on top of it, and theyre not going to be able to do anything, Crosby said.

Even if tumor-targeting T cells access the individual tumor cells, they often struggle to engage with their targets because many cancer cells reduce the expression of key immune molecules, such as MHC-I, to evade immune detection. You can have the best T cell response, and you can have the best vaccine or the best transgenic T cell therapy, but if the tumor itself is not presenting the antigen on MHC class one, then we have a big problem, because then the T cells cannot see the targets, said Schliehe.

For vaccine-generated immune cells to effectively attack and eliminate tumor cells, they must be able to penetrate the suppressive tumor environment and access their targets. This is easier to accomplish if treatments can get an early start before the tumor has a chance to establish its defenses.

You have to think about all the things that the cancer has done to the immune response to favor its survival, and thats a tough mountain to overcome, said Brian Czerniecki, a physician scientist at Moffitt Cancer Center. For cancer vaccines, the earlier they are used, the more effective they will be.

Czerniecki treats patients with breast cancer, and like many others, he targets human epidermal growth factor 2 (HER2), a driver protein that is shared across many patient tumors, using dendritic cell-based vaccines. However, in his previous clinical trials, he recruited patients who were in the early stages of cancer and administered the vaccine to the patients lymph nodes, as opposed to intravenously or intramuscularly, prior to them starting chemotherapy. He found that this cancer vaccination approach drastically shrunk tumor sizes.25 Czerniecki also found thatintratumoral vaccination in mice effectively reduced tumor sizes, offering another promising option for patients in the future.26 You can actually make this stuff disappear, he said.

To elicit an effective immune response against cancer is particularly challenging because the cancer is expecting an immune response

Eli Gilboa, University of Miami

Coupling vaccination with existing chemotherapy or immunotherapy, such as checkpoint inhibitors, to circumvent the tumor microenvironment also offers a solution to break through tumor defenses.27-29 However, the antigen still must be displayed for T cells to engage and eliminate the tumor cells, highlighting the importance of restarting MHC-I surface presentation, which is interrupted in tumor cells at times due to mutations.30 If the MHC-I gene is mutated, this may be resolved by introducing an intact MHC-I copy using a vector.31 Often though, MHC-I gene expression is only downregulated and the gene is intact, so stimulatory cytokines could be sufficient to restart expression.32 Another idea demonstrated by Schliehes group is to use small molecules called proteolysis-targeting chimeras (PROTAC), which fuse target proteins to a protein tag for cellular degradation and in turn, promote MHC-I expression.33 In tumors, these could force cells to present these antigen-bearing complexes and the mutated antigens bound to them, which can improve vaccination success.

Better identification and selection of target antigens will also continue to propel cancer vaccines forward. Advancements in sequencing and predictive algorithms to find and validate novel tumor antigens in cancers could improve the outcomes of clinical trials by targeting antigens most likely to induce successful immune responses.34

Finally, giving cancer vaccines a twenty-first century makeover may make them not only more successful, but also more accessible. Crosby and her group replaced dendritic cells with viral platforms that introduce the HER2 antigen to dendritic cells in vivo.16,17 This approach can alleviate the complications surrounding isolating, preparing, and then readministering antigen-loaded dendritic cells to patients. Furthermore, ongoing research on neoantigens, particularly shared antigens across different tumors in various patients, can improve personalized cancer vaccines and help develop widely applicable therapeutic vaccines for patients.35

After almost fifty years of hope and promise, cancer vaccines are poised to join the repertoire of immunotherapies. Alongside existing therapies, cancer vaccines may produce immune responses that make tumors more accessible, revitalize the immune response against them, and improve the actions of other regimens to target and destroy cancerous cells. However, as Gilboa explained, battling cancer is a series of stepwise successes in improving patients lives. We need patience and humility in recognizing the enormous challenge in treating cancer, he said.

References

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Cancer Vaccination as a Promising New Treatment Against Tumors - The Scientist

When COVID hit in the winter of 2020, hospitals were overflowing with the sick and dying. Public health experts worried that wed be isolating for years because, although vaccines were possible, none had ever been developed in fewer than four years. Yet, within weeks of the identification of the viruss genetic structure, two companies had settled on the basic frameworks for mRNA vaccines, which were then developed on an accelerated timeline. Just as remarkable, after six months of testing, we were told they were over 90 percent effective against COVID.

With businesses and schools operating remotely for most of 2020 and the early part of 2021, vaccines were the best hope for emerging quickly from the worst pandemic in a century. And, to a large extent, those hopes materialised. Vaccines saved countless lives and may have reduced disease transmission in early variants. But they were neither as effective nor long-lasting as had originally been touted, did not significantly lower transmission in later variants, and had nasty side-effects for a small minority. Perhaps most importantly, a large proportion of the population did not like vaccine mandates (which in many cases were deemed illegal).

The fallout from COVID vaccine policies continues, and it's not a healthy sight. Vaccine rates appear to be dropping. And trust in public health advice is falling faster if my conversations with physicians in Montgomery County, Pennsylvania, are anything to go by. This has worrying implications. As vaccination rates fall, at first the impact will be small, until it isnt. Depending on the disease and the vaccine, somewhere between 60 and 95 percent of a population must be vaccinated (or have had the disease and recovered from it) to reach herd immunity. Once rates fall below that threshold, the disease spreads rapidly. The health and economic costs of diseases such as measles, diphtheria, and smallpox were once enormous. Vaccination changed that. Indeed, smallpox was eliminated. But falling vaccination rates have already led to a resurgence in measles, a disease that deserves to be consigned to history.

Vaccines: a brilliant discovery

Over two hundred years ago, British physician Edward Jenner intentionally infected a boy with cowpox pus, hoping it would protect against the similar but far more lethal smallpox. Jenners success began the scientific formalization of centuries-old efforts to inoculate people against various maladies, in what is now known as vaccination (from the Latin for cow, vacca).

It works! It works! It works!: Jonas Salk and the Vaccine that Conquered Polio

Sydney. London. Toronto.

Vaccines were so successful and their benefits so much greater than their risks that, in the 19th century, US states began mandating smallpox vaccination for children. Although there were legal challenges to these mandates, in 1905 they were upheld by the US Supreme Court in a key decision. It is worth reading from the decision to see that the notion of compulsory vaccination campaigns is not new:

In line with the Supreme Court decision, federal agencies such as the Centers for Disease Control (CDC) have been recommending vaccinations since at least 1914 for whooping cough (pertussis), and states have been enforcing those recommendations by law.

The Pew Research Center chart below illustrates the panoply of useful vaccinations that have saved millions of lives and when they first were recommended by the CDC.

Pew also pulled together all the data on vaccine mandates, noting, Of the 16 immunizations the CDC recommends for children and teens, all 50 states (plus the District of Columbia) mandate diphtheria, tetanus, pertussis (whooping cough), polio, measles, rubella and chickenpox.

So we have been living with vaccine mandates for a long time. All except those with a medical or religious exemption have been required to take these vaccines, and the vast majority have done so without concern. And that is true across most developed nations. Growing up in England, I received most of those vaccines at roughly the same ages as my American counterparts would have (and I was required to prove that I had been vaccinated when I obtained my permanent residency here in the U.S.).

Pennsylvania, where I now live and the location of my original research, requires all of the above-listed vaccines. For children to access childcare and school, hepatitis A and B, rotavirus, Hib, pneumococcal conjugate, and influenza vaccines are also required.

And except for a few noisy skeptics, many of whom have touted discredited research that fraudulently and falsely claimed a link between autism and vaccines, these requirements have passed almost unnoticed. So, what changed with COVID?

The COVID vaccine story

With hindsight, its easy to see that COVID vaccines were oversold. The initial claims that they were more than 90 percent effective, might prevent transmission, and had no obvious side-effects didnt survive scrutiny. While obviously a lifesaver for manyparticularly those with two or more comorbiditieswithin a matter of weeks, stories of the vaccinated becoming sick and transmitting the disease to family members were rife. Vaccines did not prevent disease transmission but they did lower viral loads and hence probably reduced transmission of the Alpha variantbut not the much more virulent Delta.

Boosters were required as potency waned dramatically after about three months. The virus also mutated, becoming more virulent but less dangerous, which also changed the calculus of those considering taking the vaccine. Was it worth a sore arm and possibly a couple of sick days for a disease that, at worst, was likely to be just a bad cold for most people?

Nevertheless, federal authorities demanded vaccination even when someone had just had COVID, which was illogical given that the natural immunity provided by having contracted a disease is usually greater than the passive immunity obtained from vaccination. Social media became inflamed with stories about vaccinated young people with myocarditis who had not been infected with COVID (a rare but real, dangerous, and sometimes lethal side-effect), as well as disgust that the companies making the vaccines were making billions of dollars and were immune from prosecution when the vaccines caused harm. All the while, politiciansand scientists advising politiciansdenied problems, maintained the story of high efficacy, and mandated vaccines for work and school.

Lastly, even the strongest vaccine advocates, such as former presidential advisors Francis Collins and Anthony Fauci, admit that vaccine hesitancy has grown.

As I spoke to physicians in Montgomery County, I expected to hear that these concerns have been raised by patients, especially in the more Republican-voting areas, partly because Congressional Republicans had been vocal in their opposition to vaccine mandates and may have influenced opinion in Republican areas. My early results offer a much more nuanced picture of the nature of vaccine hesitancy following the COVID vaccination campaigns.

Physicians in Montgomery County, PA

Primary physicians oversee many vaccinations and also address many questions from patients about vaccines, including ones about efficacy and safety. Montgomery County is predominantly Democrat-voting, but two of its fourteen districts are moderately Republican. I surveyed 124 primary physicians in the county to understand what changes, if any, in vaccine uptake and opinions had occurred among their patients since the pandemic began. I also split the sample between the large, heavily Democratic area (107 physicians) and the smaller, moderately Republican area (17 physicians).

Vaccine Hesitancy and the Pandemic: Physician Survey Responses - International Center for Law & Economics

Executive Summary Vaccines for the SARS-CoV-2 virus saved countless lives and are a modern science miracle. But they had risks, were not as effective as . . .

Its important to realize that my survey data are imprecise since they are primarily based on the recall (of up to four years) of busy physicians each dealing with dozens of patients. Thus, small differences over time or between districts may well be the results of poor recall or biases due to survey design. However, significant differences could well point to identifiable trends.

As expected, nearly all patients (adults, children, and infants) received the first round of COVID vaccines in early 2021. But by the fall of 2023, far fewer adults and very few infants had taken the latest booster. This trend was even more pronounced in the more Republican areas, where fewer than half the adults had taken the latest booster (and this was confined to those with comorbidities, signaling that, under the advice of their physicians, those patients knew they were most at risk and acted accordingly). Although some evidenceindicates that Republicans are more likely to die due to lack of vaccine uptake.

According to most physicians, patients were fully aware that vaccines were less effective than had originally been touted. Physicians reported patient phrases like a small chance of myocarditis with a vaccine for a disease that would likely be a bad cold, explaining why few took the latest booster.

COVID is one disease among many; the other diseases that require vaccinations have not disappeared. Not one physician reported an increase in vaccine uptake for these other diseases, and approximately a third reported no change. Two thirds (and slightly more in the Republican areas) saw a decrease in vaccination uptake. This is a very broad measure. More detailed surveys are required to understand exactly what types of vaccines are being missed: the yearly and not particularly effective flu vaccines; or the far more important and less frequent (often a one-off in childhood) vaccines for diseases such as measles, polio, and tuberculosis. We also do not know by how much vaccine rates are falling.

Nevertheless, that rates are falling is potentially worrying and deserving of attention.

I asked the physicians: Is it just the risks of COVID vaccines that are leading to a decline in all vaccination rates?

Most physicians report patient concerns about the safety of COVID and, increasingly, other vaccines. Patients are uncertain of, but worried about, social media reports of vaccine harm. One can scoff at social media as a source of scientific truth, but as one physician said, Given that social media was the only place that supported the notion that SARS-CoV-2 came from a lab or that drugs like Ivermectin might work, were [patients] wrong to believe it? Social media allowed discussion of other theories and concerns, some of which turned out to be true; thus, many patients were inclined to worry. These patients were less likely than average to take the vaccine and were definitely not likely to let their children. Some of these patients talked about the lies told by health authorities; Anthony Fauci was named repeatedly.

More than a few patients were apparently very angry about having to take a mandatory vaccine that might be unsafe and was not clinically required if one had recently had the disease. Even some physicians were concerned about the scientific illiteracy of health authorities demanding COVID vaccines be administered to people who had recently had the disease. This led to a total distrust of vaccine policy among some patients, which definitely led to a lowering of flu vaccine uptake. Its too early to tell for other vaccines, said one physician.

Physicians mentioned several other concerns of patients ranging from arguably sensible ones such as distrust of pharmaceutical companies and the incompetence of government officials to more outlandish claims, for example, that tracker chips are inserted into vaccines and that the vaccines cause cancer. As one physician put it, when government advice is unreliable, people can believe almost anything. For some people, every unexplained young death is now attributed to COVID vaccines.

Vexed by the Un-Vaxxed

Civil society is based on the fundamental premise that we give up certain liberties to secure tranquility, defense, welfare, and greater liberty, such as the freedom from fatal diseases.

One can understand the desire of health authorities to get everyone vaccinated. With herd immunity only being achieved through high levels of vaccination or recovery from disease, it is entirely reasonable to encourage vaccination. But the conclusion from my survey is that misleading the public and overselling the vaccines backfired and played into the hands of perennial anti-vaxxers.

It is not that surprising that uptake of COVID vaccine boosters by infants and children collapsed last year and fell markedly among adults. One comment made by a few physicians was that uptake was close to zero for adults under 40 while it was nearly universal among adults over 70 and those with comorbidities. This suggests that much of the public has a good understanding of the scientific situationwith those most at risk from COVID taking the vaccine and those least at risk choosing to avoid the side-effectswhich is very positive news.

The lesson for health authorities is that they should trust people to understand the science and do what is in their self-interest instead of badgering them with simplistic (and often incorrect) information. While the Supreme Court has confirmed the right of federal authorities to impose vaccine mandates, and vaccine technology has improved so that vaccines can be designed and produced rapidly, it does not mean authorities should mandate vaccines. Or if they do, they should reassess the mandates routinely so as not to undermine public confidence in their authority.

Link:

Vaccine Hesitancy and the Covid Pandemic - Quillette

During the childs October 511 health care encounters, 247 health care workers and 177 patients and patient companions were considered to have been exposed, including 13 children aged <1 year, five immunosuppressed children, and one child aged >1 year with no history of MMR vaccination. Among these 19 children, two received a dose of MMR vaccine within 72 hours of the exposure, and 13 received immune globulin.

The index patients household contacts included two siblings with no history of MMR vaccination and with serologic testing indicating measles susceptibility. One sibling, aged 4 years, (patient B) arrived in the United States at the same time as the index patient (September 29). The second sibling, aged 9 years, (patient C) had arrived in the United States in January 2023. Both siblings developed measles while in quarantine with rash onsets on October 22 (patient B) and November 1 (patient C). Patient B also reported fever, cough, coryza, and conjunctivitis; patient C also reported fever. Neither child was hospitalized, although patient B required an ED visit at hospital A for supportive care. On October 17, exposure notification letters were delivered to all residents in the apartment building where the index patient lived.

On October 30, hospital A notified CCDPH of another child, aged 2 years, (patient D) who had been evaluated in an ED early that morning with fever, cough, and coryza, then discharged. The family of that child lived in the same 2-story apartment building as the index patient, but on a different floor. Patient D had no history of MMR vaccine; the childs parents reported objections to MMR vaccine based on personal beliefs and perceptions about vaccine side effects. Measles was confirmed in this child by RT-PCR testing on October 30; rash onset occurred on November 1. The families of patients AC and patient D had different cultural backgrounds from one another and spoke different primary languages; both families independently reported no contact with the other family. Their apartment units did not have shared ventilation; however, laundry facilities and building entrances were shared.

On October 31, testing was also performed for a sibling of patient D, a child aged 1 year (patient E), also with no history of MMR vaccine, who had isolated coryza and who attended a child care facility on October 30 while symptomatic; a nasopharyngeal swab collected in the home confirmed measles by RT-PCR testing. Attendees and staff members of the child care facility were notified the same day. One child aged 2 months received immune globulin, one child aged 11 months received 1 dose of MMR vaccine, and 11 children who had received their first MMR vaccine dose received an early second dose as post-exposure prophylaxis.** Fever in patient E did not occur until November 6, and rash did not appear until November 9, which was 9 days after the positive RT-PCR test result and child care facility notification. Measles testing is indicated for susceptible contacts of measles cases when the contact has prodromal symptoms (i.e., fever, cough, coryza, or conjunctivitis); however, isolated coryza experienced by this patient at the time of specimen collection might not have been related to measles. Because testing for measles before fever onset is not typically performed, an accurate infectious period for this patient was difficult to ascertain. Patient Es symptoms resolved without requiring emergency care or hospitalization. This activity was reviewed by CDC, deemed not research, and was conducted consistent with applicable federal law and CDC policy.

Originally posted here:

Notes from the Field: Measles Outbreak Cook County, Illinois, OctoberNovember 2023 | MMWR - CDC

Astudy today in the New England Journal of Medicine discusses a phase 3 randomized, controlled trial of GSK's respiratory syncytial virus (RSV) vaccine in pregnant women that was stopped early owing to an increased risk of preterm birth.

Researchers from GSK and the Duke University School of Medicine assessed the efficacy and safety of the RSVPreF3-Mat vaccine in 5,328 pregnant women aged 18 to 49 years and 5,233 infants from November 2020 to February 2022, when enrollment and vaccination were stopped after a link to preterm birth was noted.

The trial was conducted at sites in 24 countries on six continents, with roughly half of the participants in the vaccine and control groups from low- and middle-income countries (LMICs). The team randomly assigned participants in a 2:1 ratio to receive either RSVPreF3-Mat or a placebo between 24 and 34 weeks' gestation. In total, 3,426 infants whose mothers received the vaccine and 1,711 infants whose mothers received placebo were followed from birth to 6 months.

RSV is a leading cause of lower respiratory tract disease in children and can be particularly severe in infants younger than 6 months old, especially those in LMICs.

In July 2023, the US Food and Drug Administration (FDA) approved nirsevimab (brand name, Beyfortus), a long-acting monoclonal antibody,for RSV prevention in infants. In August 2023, the FDA approved the first RSV vaccine based on the RSV prefusion F protein (Pfizer's bivalent [two-strain] RSVPreF; brand name, Abryvso) for pregnant women from 32 to 36 weeks' gestation; it isn't given before 32 weeks' gestation because of a potential risk of preterm birth. Abryvso is also approved for use in people aged 60 years and older.

RSVPreF3-Mat is a monovalent, or single-strain, vaccine.

Sixteen and 24 infants in the vaccine and placebo groups, respectively, had medically assessed RSV-associated lower respiratory tract disease (vaccine effectiveness [VE], 65.5%; 95% credible interval [CrI], 37.5% to 82.0%), and 8 and 14, respectively, had severe RSV (VE, 69.0%; 95% CrI, 33.0% to 87.6%).

Of the 3,494 infants in the vaccine group, 237 (6.8%) were born early, compared with 86 of 1,739 (4.9%) in the placebo group (relative risk [RR], 1.37). Also 13 of 3,494 (0.4%) and 3 of 1,739 (0.2%), respectively, died (RR, 2.16), an imbalance seen primarily in LMICs (RR, 1.56 vs 1.04 in high-income countries). The authors said the disparity was likely at least partly attributable to the greater percentage of preterm births in the vaccine group.

The results of this trial, in which enrollment was stopped early because of safety concerns, suggest that the risks of any and severe medically assessed RSV-associated lower respiratory tract disease among infants were lower with the candidate maternal RSV vaccine than with placebo but that the risk of preterm birth was higher with the candidate vaccine.

In other words, for every 54 infants born to vaccine recipients, 1 additional preterm birth occurred, with the time from vaccination to preterm birth varying from weeks to months. Among the infants born early, very preterm birth (28 to 32 weeks' gestation) or extremely preterm birth (less than 28 weeks' gestation) occurred in 13 of 237 (5.5%) in the vaccine group and 2 of 86 (2.3%) in the placebo group. No other safety signals were reported.

"The results of this trial, in which enrollment was stopped early because of safety concerns, suggest that the risks of any and severe medically assessed RSV-associated lower respiratory tract disease among infants were lower with the candidate maternal RSV vaccine than with placebo but that the risk of preterm birth was higher with the candidate vaccine," the researchers wrote.

In a related commentary, Sonja Rasmussen, MD,of Johns Hopkins University, and Denise Jamieson, MD, MPH, of the University of Iowa, noted that it's unknown whether the safety signal in the RSVPreF3-Mat trial was real or a chance event.

Given the findings of the present trial and the modest imbalance in the incidence of preterm birth in the phase 3 trial of the bivalent vaccine [Abryvso], postmarketing surveillance of the bivalent vaccine is warranted.

"Despite many post hoc analyses, the authors were unable to identify a mechanism by which the receipt of RSVPreF3-Mat might have increased the risk of preterm birth," they wrote. "However, given the findings of the present trial and the modest imbalance in the incidence of preterm birth in the phase 3 trial of the bivalent vaccine [Abryvso], postmarketing surveillance of the bivalent vaccine is warranted."

"Even if there is a true association between the receipt of the bivalent vaccine and preterm birth, it is essential to weigh this small risk against the proven benefits of maternal RSV vaccination," they added. "Moreover, any potential risk of preterm birth associated with the receipt of the bivalent vaccine is reduced by the administration of the vaccine at 32 weeks or more of gestation."

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Study details why phase 3 trial of GSK's RSV vaccine for pregnant women was halted early - University of Minnesota Twin Cities

The Centers for Disease Control and Prevention updated its guidance Wednesday for travelers in the wake of a global rise in measles outbreaks, as cases have mountedacross 17 states.

Americans planning to travel abroad should consult their doctors at least six weeks before traveling if they are unsure about whether they are up to date on their vaccines, the agency now says, in order to avoid catching the highly contagious virus during their trip.

The CDC previously said in November that travelers only needed to schedule an appointment at least one month before their trip, in order to have enough time to get vaccinated.

click to expand

Russia and Malaysia were also added Wednesday to the CDC's map of 46 countries now facing large measles outbreaks. However, the agency warns that the global rise in measles cases remains a threat in other parts of the world too.

"Measles spreads rapidly and may become a risk to travelers in places not included on the list above. CDC recommends all travelers are fully vaccinated against measles when traveling to any international destination," the agency says.

It is not clear what prompted the CDC's new measles guidance tweaks. A spokesperson for the agency did not immediately answer a request for comment.

In recent weeks, health authorities have ramped up their plea for Americans to get vaccinated before spring break travel this year.

Officials have cited recent outbreaks linked to travelers who were infected abroad and had been eligible to be vaccinated.

Those include a cluster over the winter in Philadelphia, linked to an unvaccinated baby. The infant had been old enough to get a shot of the measles-mumps-rubella or MMR vaccine, which is recommended for travelers at least 6 months old.

Another had been in Idaho, which state health authorities linked to an unvaccinated adult who traveled to Europe, where many countries are now facing resurgent outbreaks of the virus.

"The World Health Organization has noted a significant increase in measles cases worldwide, with a 30-fold increase in Europe. This includes popular international tourist destinations for Americans, like England," the CDC said in a report on March 8.

Two doses of MMR vaccine offers 97% protection against measles, the CDC says, and at least one dose offers 93%. The shot offers lifelong protection against measles.

Most Americans got two doses of the vaccine by the time they were 6 years old, under CDC recommendations and widespread school requirements, though vaccination rates have slipped in recent years.

For adults born after 1957 who are unsure if they are protected, all are recommended to get at least one dose of the vaccine if they do not have evidence of immunity, like records of vaccination or previous infection.

In the United States, state and local health authorities have announced at least 55 confirmed or suspected cases of measles so far this year across 17 states.

That is close to the 58 total measles cases the CDC says were reported for all of 2023. The last peak of yearly measles cases was in 2019. That year 1,274 infections were reported, making up the most on record in a single year since 1992.

Most new cases in the past week have been in Illinois, where Chicago health authorities have been responding to an outbreak in a migrant shelter. That outbreak prompted the deployment of CDC and state teams to aid the response, as the city has sought to screen and vaccinate hundreds potentially exposed.

New infections have also been announced over the past week in California and Arizona.

A spokesperson for the California Department of Public Health said Wednesday there were four reported measles cases statewide, and that "cases have been linked to travel to countries with epidemics in the wake of decreased routine immunization."

Hundreds may have been exposed at a hospital in Sacramento, authorities warned on March 8, after a child contracted the virus following a trip outside of the country.

State officials said their measles trends remain "similar to pre-pandemic levels" so far.

Officials in Arizona's Coconino County also announced a new case on March 11. Three previous infections were reported this year in Arizona's Maricopa County, which spans Phoenix, but the new case wasn't linked to those or to international travel, a county health and human services department spokesperson said Tuesday.

Alexander Tin is a digital reporter for CBS News based in the Washington, D.C. bureau. He covers the Biden administration's public health agencies, including the federal response to infectious disease outbreaks like COVID-19.

The rest is here:

Going abroad? Time to check if you're up to date on measles immunity, CDC says - CBS News