Category: Vaccine

COVID-19 was the first global outbreak for which a brand new vaccine was developed in just one year. This was lightning fast compared to previous vaccine development efforts, but in 2021, countries like the UK and US came up with a radically more ambitious goal of producing vaccines, diagnostic tests and treatments for scaling up within 100 days of a pandemic threat being identified.

Now, Japan has announced it will invest US$ 2 billion in achieving the same goal through its Strategic Center of Biomedical Advanced Vaccine Research and Development for Preparedness and Response (SCARDA), due to formally launch next month.

The intensified spread of COVID-19 through the emergence of highly contagious variants such as Omicron was a factor in the creation of the centre. In late 2021, Prime Minister Fumio Kishida said he wanted to fundamentally reinforce crisis management.

Early in the pandemic, Gavi and partners set up the COVAX facility to ensure equitable access to COVID-19 vaccines and a market for manufacturers supplying them. For organisations like Gavi, Japans investment is welcome, paving the way for future collaborations with Japan in the case of future pandemics.

In March this year, the global health community came together at The Global Pandemic Preparedness Summit, led by the UK government and the Coalition for Epidemic Preparedness Innovations (CEPI), to turn the moonshot goal of a 100-day vaccine into a reality.

Compressing the vaccine development timeline to just 100 days will mean as much preparation as possible. This means anticipating future threats a universal vaccine against coronaviruses is high on the list as three coronaviruses (MERS-CoV, SARS and COVID-19) have caused global outbreaks already.

Another goal to speed up vaccine development will be to build a library of vaccine candidates against other threats. The ability to leapfrog from work done on MERS vaccines, for instance, meant that COVID-19 vaccine development could be sped up.

Developing a vaccine in 100 days will need to be followed by rapid scale-up, and there will also need to be investment in manufacturing innovations that can support scale-up, especially in low-income settings.

Japanese researchers speaking to Nature said that the country appreciates the value of developing research capacity and early, preparatory investment in vaccines so that when an emergency does arise, the country is ready to respond. Although the country did invest in COVID-19 vaccine development, nearly three years after the pandemic started the most advanced vaccine candidates are still in clinical trials and not approved for use.

Of the $2 billion, $1.2 billion will go to vaccine research and development projects, and $400 million to support start-ups in drug development. The final $400 million will create a virtual network of centres of excellence for basic research in vaccine science as well as testing vaccine candidates in early-stage trials.

The centre will invest in vaccine research for eight pathogens, including coronaviruses, monkeypox, dengue virus and Zika virus. The vaccines being developed include a range of delivery technologies, such as mRNA technology (that was used for some COVID-19 vaccines), viral vectors and recombinant proteins. The idea is to find seeds for future vaccines, Dr Yoshihiro Kawaoka, a virologist at the University of Tokyo told Nature.

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Japan invests to ensure pandemic vaccines can be made in 100 days - Gavi, the Vaccine Alliance

The HIV virus mutates at a really high rate, he says. We hear so much about variants of COVID-19, but it doesnt mutate nearly as rapidly as HIV does.

Whats more, the HIV virus has a different structure that sets it apart from other common viruses, Wessner notes. The surface proteins on it are heavily coated with sugars, he says. This makes it harder for our immune system to recognize the virus proteins and mount a response.

Theres one more hurdle that makes the development of an HIV vaccine challenging: When youre exposed to a virus, either through infection or a vaccine, your body develops antibodies, or proteins that your immune system makes to help fight the virus. These antibodies also protect you against future infection. But most people infected with HIV dont develop whats known as broadly neutralizing antibodies, which are needed to fight variants, as they do with other viruses, Wessner explains. That means their bodies cant clear the virus after an initial infection, and it also makes it much harder for potential vaccines to block new infections.

The mRNA vaccines approved to prevent infection with COVID-19 were revolutionary. And the exact same technology may be what gets us to the finish line for an HIV vaccine, says Steven Deeks, M.D., an HIV specialist, vaccine researcher and professor of medicine at the University of California, San Francisco (UCSF).

AnmRNA vaccineworks by delivering a piece of genetic material that instructs your body to make a protein fragment of the virus, which your immune system recognizes and remembers, so it can create a robust immune response if its exposed to it again.

With this technology, we can develop new vaccines and test them much more quickly than we did in the past, Deeks says. This means researchers will be able to design vaccines rapidly and learn whether they are able to create the broadly neutralizing antibodies required for a successful HIV vaccine.

But the COVID-19 pandemic has also created some hurdles for vaccine development.

Weve seen a lot of setbacks in our HIV goals, as resources that could have gone towards HIV vaccine research went towards creating a COVID-19 vaccine instead, says Monica Gandhi, M.D., professor of medicine and director of the UCSF Center for AIDS Research in San Francisco. In addition, there are concerns that some of the vaccine hesitancy seen during the COVID-19 pandemic could spill over to an HIV vaccine, when one is finally developed, Wessner says. We saw this with the human papillomavirus vaccine as well, he says. There may be a lot of resistance if an HIV vaccine becomes available to the general public.

Up until recently, the most promising line of research was investigating whether injecting healthy people with broadly neutralizing antibodies can protect against HIV. Scientists mass-produced one antibody, known as the VRC01 antibody, discovered in the blood of a patient living with HIV.

Initial research suggested that it might be up to 75 percent effective in preventing HIV transmission. Buta 2021 studythat followed more than 4,000 at-risk people for 20 months found that this antibody was able to block only about 30 percent of the HIV strains circulating in a community.

Go here to read the rest:

Will We Ever Have a Vaccine for HIV? - AARP

In a recent study published in JAMA Network, researchers described the human monkeypox virus infection after vaccination with the modified Vaccinia Ankara-Bavarian Nordic (MVA-BN) vaccine.

MVA-BN is a live, non-replicating vaccination that protects adults from contracting smallpox and monkeypox. While immunogenicity studies point to substantial response rates following the two-dose series with MVA-BN vaccination, evidence of clinical use effectiveness is scarce. Since local health departments struggle to procure MVA-BN, many have adopted a single-dose strategy to utilize the current supply best. Additional strategies to administer lower volume doses intradermally have also been employed.

The present study described monkeypox infections observed following a single dose of MVA-BN.

Howard Brown Health (HBH) started using real-time reverse transcriptase-polymerase chain reaction (RT-PCR) testing to identify monkeypox in May 2022. On June 28th, 2022, HBH started distributing MVA-BN to qualified individuals. The study included individuals who tested monkeypox positive between June 28th, 2022, and September 9th 2022, a minimum of one day after receiving the first dose of the MVA-BN.

From the electronic medical record (EMR), all instances of monkeypox-positive cases during the study period were retrieved. The EMR and a study of a statewide computerized database for the exchange of immunization records were then used to determine the patient's vaccination status.

Following vaccination, confirmed cases of monkeypox were divided into four groups based on the number of days until positivity- one to seven days, eight to 14 days, 15 to 28 days, and more than 28 days. The EMR was used to extract information on demographics, human immunodeficiency virus (HIV) status and virologic suppression, and use of HIV preexposure prophylaxis.

During the trial period, 7,339 people at HBH received their first dosage of MVA-BN, while 400 patients tested positive for monkeypox. Among 90 individuals who tested monkeypox-positive a minimum of one day after immunization, 73.5% displayed viral loads less than 200 copies/mL, 91% were cisgender, and 37.8% had HIV.

The team noted that 37 cases occurred one to seven days while 32 cases were reported eight to 14 days after vaccination. This accounted for 77% of all cases diagnosed after vaccination. It took an average of 8.5 days from vaccination to infection. Furthermore, 36.2% of the cases that occurred one to 14 days after vaccination were HIV-positive individuals, 96% of whom were virologically suppressed. Preexposure prophylaxis was used by 54% of early post-vaccination cases that did not have HIV infection.

Two instances of monkeypox occurred more than 14 days after the second dosage of MVA-BN, which were included in the total eight cases diagnosed 28 days after the first MVA-BN vaccination. All eight patients identified as cisgender males, 50% of whom had HIV and were virologically suppressed. Less than ten lesions were observed in all patients except one. Due to the severity of their anogenital symptoms, one patient received tecovirimat antiviral medication.

Overall, the study findings showed that most monkeypox-positive cases noted after MVA-BN vaccination occurred within two weeks of the first dose before the vaccine was likely to display full efficacy.

Read more here:

Study finds the majority of post-vaccination monkeypox infections occur within 2 weeks of receiving the first dose of MVA-BN - News-Medical.Net

A study funded by the Centers for Disease Control and Prevention (CDC) has found a positive association betweenvaccine-related aluminum exposure and persistent asthma.

The study (pdf), published on Sept. 28 in themedical journal Academic Pediatrics, sought to assess the association between cumulative aluminum exposure from vaccines before age 24 months [2 years of age] and see whether this group of children developed asthma between ages 2 and 5.

Authors of the retrospective cohort study included current and former CDC staffers. They analyzed data from a cohort of326,991 children whowere born between 2008 and 2014 at seven medical care organizations across the United States that participate in theVaccine Safety Datalink, a network of health groups that collaborate with the CDC in studying vaccine safety.

Results of the observational study showed that children who were vaccinated with most or all of the recommended aluminum-containing vaccines (>3.00 mg aluminum exposure) had at least a 36 percent higher risk of being diagnosed with persistent asthma than kids who got fewer vaccines (3.00 mg aluminum exposure).

About 6 percent of the children with eczema and 2.1 percent of the children without eczema developed persistent asthma in the study.Each additional milligram of vaccine-related aluminum exposure was associated with 1.26- and 1.19-times higher rates of persistent asthma among children with and without eczema, respectively.

Overall, there was a positive association between vaccine-related aluminum exposure and persistent asthma, the authors said. They did not conclude that the results suggest any causative link. [A]dditional investigation of this hypothesis appears warranted, they added.

On its website, the CDC said that itis not changing vaccine recommendations based on this single study, but further investigation is needed into this potential safety signal.

In a statement to multiple outlets, the agency noted that the study has important limitations that the authors acknowledge. It added about the study, We recognize these results may sound concerning to some parents, but there continues to be overwhelming evidence of the benefits of vaccines.

The studys lead author, Matthew Daley, said that even if a link were found between vaccine-related aluminum exposure and persistent asthma, the benefits of the vaccines are still likely to outweigh the asthma risk. But in such a case, the link could possibly prompt new work to redesign vaccines, he said.

Several previous studies didnt find a link between aluminum-containing childhood vaccines and allergies and asthma. But other research has linked aluminum in industrial workplaces to asthma. And mice injected with aluminum suffer an immune system reaction that causes the kind of airway inflammation seen in childhood asthma.

Based on what I consider limited animal data, there is a theoretical risk that the aluminum in vaccines could influence allergy risk, Daley said.

The study was prompted in 2013 after the Institute of Medicine, now known as the National Academy of Medicine, called for more federal researchinto the safety of childhood vaccines, including their use of aluminum.

By age 2, children should be vaccinated against 15 diseases, according to U.S. recommendations. Aluminum adjuvants are in vaccines for seven of them.

According to the CDC on itswebsite,Aluminum-containing adjuvants are vaccine ingredients that have been used in vaccines since the 1930s. An adjuvant is an ingredient used in some vaccines to help spark a stronger immune response. In other words, adjuvants help vaccines work better, according to the CDC.

Adjuvanted vaccines can cause more local reactions (such as redness, swelling, and pain at the injection site) and more systemic reactions (such as fever, chills and body aches) than non-adjuvanted vaccines, the CDC website reads.

The agency noted that aluminum is among the common metals found in nature and is present in air, food, and water.

Increased rates in allergies and asthma among children in the United States were noted during a 30-year period starting in about 1980, and some scientists wondered if there was a connection between that and vaccines that contained aluminum.

The CDC pointed out toSTAT in an emailed statement that the increase in asthma among young children starting around 1980 is before aluminum was added to vaccines, which was around 1991.

It also told the outlet that other factors that could not be measured by the study authors could have contributed to an increase in asthma in children.These include family history of asthma, secondhand smoking, as well as other ways of exposure to aluminum or other contaminants via diet or the environment that may contribute to poor health and contribute to the childs asthma.

We hope that additional studies can quickly provide more clarity, but at least from the national trend data, it appears that addition of aluminum-adjuvanted vaccines do not account for the overall trends that we see, the CDC told STAT.

Brian Hooker, the chief scientific officer for Childrens Health Defense, said that the study has conceded that asthma [is] correlated with aluminum exposure in both children with eczema and children without eczema.

He noted that the CDC-funded study did not compare results of the vaccinated children with children who werent exposed to aluminum at all in their vaccines. A true comparison should be [done] between the maximum aluminum exposure at 2 years of age (which is about 4 mg total injected aluminum adjuvant) and a zero exposure group, he said, reported The Defender.

Hooker cited an analysis he authored with Neil Miller, published in 2020, that showed an odds ratio of 4.49 (statistically significant) for asthma in vaccinated children versus unvaccinated children. He said the analysis was based on cases of vaccines in the first year of life. The CDC seems to be confirming my results here, he said.

The Associated Press contributed to this report.

Read more:

'Positive Association' Between Vaccine-Related Aluminum Exposure and Persistent Asthma: CDC-Funded Study - The Epoch Times

Vaccines are critical to global health security, being the most effective form of prevention and control of the spread of communicable diseases, some of which are particularly serious and potentially life-threatening. Vaccines crucial role and high-priority nature become even more evident in cases of pandemic, endemic or epidemic events.

Despite the major role of vaccines in healthcare systems on a global level, few countries explicitly indicate which pricing mechanisms they are subject to as part of the traditional pricing and reimbursement (P&R) process. Germany is one of the most striking cases, reportedly using international reference pricing (IRP) for vaccines to calculate discounts paid by pharmacies to the statutory health insurance funds. Otherwise, their characterisation within P&R frameworks is generally shrouded in ambiguity, with no specific mention of vaccines with respect to core pricing legislation. This produces substantial uncertainty on whether the same rules are applied, or rather if they benefit from any plausible exception.

Vaccine manufacturers are, therefore, required to make additional efforts in understanding the various national regulatory landscapes, the consequence of which leads to important challenges in optimising their market access and pricing strategy across multiple markets worldwide.

The 2022 edition of GlobalDatas International Reference Pricing (IRP) Strategic Guidebook responds to this need to provide greater clarity in the field, integrating the results of extensive screening and interpretation of legislation and broader regulatory frameworks complemented by primary research insights. The newly added section on IRP and Vaccines provides an immediate repository investigating how vaccines are considered within the P&R setting, with a specific focus on IRP application, taking concrete action to navigate the prevailing opaqueness of the subject.

The deep-dive investigation covers a total of 30 markets worldwide, across all regions: Albania, Algeria, Austria, Azerbaijan, Bahrain, Belgium, Bosnia and Herzegovina, Brazil, Bulgaria, Canada, Croatia, Cyprus, Denmark, Finland, France, Germany, Greece, Ireland, Italy, Japan, Moldova, North Macedonia, Norway, Romania, Saudi Arabia, Slovakia, Slovenia, Spain, Switzerland, and Turkey.

The analysis reveals that vaccines are not exempted from IRP considerations, and should represent an integral part of a vaccine manufacturers comprehensive launch and pricing strategy. While IRP applies without any exception in only six cases, ten countries allow IRP application if specific conditions are met. For an additional 12 geographies, there is concrete potential IRP could apply the same way as for any other drug, even if final decisions might be case-dependent. Just two markets do not make use of IRP while evaluating vaccines as part of the traditional P&R process.

Among countries applying IRP to vaccines, it is worth noting that only a few of them have introduced a different pricing mechanism more favourable to vaccines provided their role is deemed critical to public health or essential by the World Health Organisation (WHO). As an additional reflection, combination vaccines are surrounded by an even more heightened degree of uncertainty, with pricing mechanisms potentially adjusted to mirror the ones applied to combination drugs more generally.

The 2022 edition of the GlobalData International Reference Pricing (IRP) Strategic Guidebook also includes one more new section on IRP and Combination Drugs with a deep-dive investigation across 23 countries into IRP applied to fixed-dose combination drugs (FDCs), in the attempt to provide more clarity on this topic as well. Only nine markets present separate pricing mechanisms for FDCs from that of single-INN drugs.

Learn more about the GlobalData International Reference Pricing (IRP) Strategic Guidebook, 2022 edition.

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IRP and vaccines: navigating the uncertainties - Pharmaceutical Technology

A large collective of researchers may be one step closer to developing a vaccine against HIV after engineering a protein that triggers a widespread antibody response.

Scientists have identified promising broadly neutralizing antibodies (bnAbs) that could be used to create a vaccine against HIV, according to a study conducted by Scripps Research, IAVI, the Ragon Institute, and Moderna, Inc.

Human genes make bnAbs, which are antibodies that can fight against multiple variants of a virus. The idea behind creating this vaccine is to identify the right types of bnAbs and human genes to create an mRNA vaccine that prevents the infection or spread of HIV.

Our 2 studies describe a collaborative effort to genetically and structurally understand bnAbs, and ultimately reverse engineer vaccines to elicit these bnAbs, said senior author William Schief, PhD, a Scripps Research professor and executive director of vaccine design at IAVI's Neutralizing Antibody Center at Scripps Research, in a press release.

The research teams from Scripps and IAVI first engineered a priming immunogen for (what would be) the first dose of the HIV vaccine. This manufactured spike protein would bind to specific nave B cells, also called germline precursors.

Nave B cells are antibody-producing white blood cells, and bnAbs come from these cells. The team analyzed 1.2 billion antibody sequences in a large database, which revealed 2 bnAbs that contained the most nave B cells. The team suggested that these 2 bnAbs would thus be the best defense against HIV.

Finding the bnAbs we need is like searching for a needle in a haystack, said co-first author Zachary Berndsen, PhD, assistant professor of biochemistry at the University of Missouri, in a press release. To make an effective vaccine, we must first find the precursor antibodies that can eventually become bnAbs, while also seeing if those precursor antibodies are common enough throughout the general population to stimulate.

The researchers then collaborated with researchers from Ragon Institute. They tested the engineered HIV spike protein in mice and found that it did elicit a response in germline precursor cells. This results in a nave B cell that expresses the apex bnAbs, which can defend against the virus.

This is a very important step, as it shows that vaccinating with our immunogen can actually elicit responses from the precursors we were targeting, said co-first author Jordan Willis, PhD, senior principal scientist at the IAVI Neutralizing Antibody Center at Scripps Research, in the press release. We also showed that vaccinating with an unmodified HIV protein could not elicit those responses, which proves that our affinity engineering was required."

The HIV mRNA vaccine, which would come from Moderna, would be similar to the COVID-19 vaccine. The benefits are that mRNA vaccines are easier and faster to manufacture, and provide better antibody responses compared to a normal vaccine. The researchers anticipate that they will eventually test this vaccine in human clinical trials.

We and our collaborators are building on this approach, developing and testing immunogens to drive the later stages of bnAb maturation, said Facundo Batista, PhD, associate director of the Ragon Institute, in the press release.

Reference

Scripps Research Institute. Scientists design and validate promising HIV vaccine strategy. EurekAlert. October 3, 2022. Accessed on October 5, 2022. https://www.eurekalert.org/news-releases/966725

Original post:

Researchers Suggest That Engineering Specific B Cell Response Could Make the First HIV Vaccine Possible - Pharmacy Times

Vaccination strategies to manage animal health continue to evolve with advances in technology to produce and administer vaccines. In general, vaccines activate adaptive immunity in animals to a specific pathogen. The animal can then be more resilient to that specific pathogen exposure later in life. However, the impact of nutrition during vaccination on vaccine efficacy and subsequent animal performance is quite unclear.

Spray-dried plasma (SDP) is commonly used in pig diets to mitigate some of the detrimental effects associated with excessive immune system activation caused by abrupt dietary changes, environmental and behaviour stress and pathogen exposure during the post-weaning period. SDP is a mixture of functional proteins including albumen, globulin, transferrin, peptides, growth factors and other components that improve diet digestibility, growth, feed efficiency, health and survival of animals. SDP modulates the efficiency of the activated immune system to return to homeostasis more rapidly. It thereby spares more nutrient use for productive purposes.

In mice and layers, immunity was modulated after dietary supplementation with SDP. So what about pigs?

During the widespread emergence of porcine circovirus diseases, and specifically porcine circovirus 2 (PCV2) systemic disease, some vaccination strategies proposed to vaccinate pigs around weaning even though weaned pigs typically experience post-weaning stress and lowered feed intake and have non-mature immune systems.

Multiple studies have shown that starter diets containing SDP increase post-weaning growth and feed intake and improve feed efficiency. A study was conducted with weaned pigs to determine the effects of vaccination with a combined vaccine against PCV2 and Mycoplasma hyopneumoniae (M. hyo) or saline injected at day 3 post-weaning and fed a starter diet for 14 days post-weaning with 0% or 6% SDP on antibody development and wean-to-finish performance of pigs.

After pigs were moved to the grow-finish facility (day 63 of study), 1 pig per pen was inoculated with PCV2 virus to expose the other pigs to the virus. Regardless of the starter diet fed, vaccinated pigs maintained a much higher seropositivity against PCV2 throughout the wean-to-finish periods, while non-vaccinated pigs experienced declining antibody levels up to day 63 of the study and then increasing levels towards the end of the finishing period after their exposure to PCV2.

Furthermore, pigs fed the starter diet with SDP had improved growth during the initial 14 days after weaning, independent of vaccination. Cumulative mortality was reduced for pigs fed the starter diet with SDP by the end of nursery phase (day 48 of study) and by the end of the finishing period (day 145 of study), while vaccinated pigs had reduced mortality from day 48 to day 145. Mortality during the nursery period was primarily associated with bacterial infections. Both the vaccinated pigs and those fed the starter diet with SDP had a heavier carcass weight.

These results suggest that the higher nutrient intake of pigs fed the starter diet with SDP during vaccination and the post-weaning stress period improved their resilience against secondary bacterial infections. In conclusion, the strategy of using SDP in the starter diet along with vaccination supported the best long-term beneficial effects on survival to market and carcass weight in this study.

Since African Swine Fever virus (ASFv) has become widespread in several countries, efforts to develop an effective vaccine have progressed, with some promising prototypes under development. This year (2022), a team around the Institute of Agrifood Research and Technology (IRTA-CReSA) in Spain compared the efficacy of BA71CD2, an experimental vaccine prototype, using pigs fed with diets containing either 0% or 8% porcine SDP and later put in direct contact with pigs infected with ASFv Georgia 2007/01.

The team used 24 weaned pigs randomly divided into a group of 16 test pigs and 8 trojan pigs.

8 vaccinated test piglets received a diet containing porcine SDP.

8 vaccinated test piglets received a control diet.

8 non-vaccinated trojan piglets received the control diet. The team injected them with ASFv during the trial to provide contact exposure of ASFv to the test pigs.

Initially, the team divided the test pigs into 2 groups of 8 pigs. On day 24, they administered 2 ml of the candidate vaccine BA71CD2 to all test piglets. On day 19 after vaccination, they injected the 8 non-vaccinated trojan pigs with 1 ml of ASFv-strain Georgia 2007/01. 2 days later, they placed 4 trojans with the SDP group, and the other 4 with the control diet group. They euthanised the trojan pigs when they started showing clinical symptoms. 2 test pigs per group died because of reasons not related to ASFv, meaning that 6 test pigs per group completed the study.

As expected, all vaccinated pigs survived the ASF challenge. The team did however observe significant differences between the groups.

During the exposure period, 4 out of pigs did not have fever, while the other 2 pigs had mild transient fever. At sacrifice time, tissues from 5 of the 6 vaccinated control group pigs were PCR positive for ASFv, albeit as expected for the dose of the vaccine used, showing higher cycle threshold (Cts; lower ASFv nucleic acid load) than trojan pigs.

None of the pigs fed SDP had fever, and they all remained free of ASFv in the blood at all times after the challenge. Their tissues were all PCR negative at the end of the study (see Table 1), indicating sterilising protection.

Under the conditions of this study, 8% porcine SDP in feed improved the ASFv vaccine prototype efficacy. In other words, pigs fed the diet with SDP showed lower virus load in nasal secretion. There was no virus presence in blood or faeces after a challenge with the virus strain Georgia 2007/01, when compared to those fed a control diet.

In addition, the team did not detect virus in any organ tissue of the pigs fed SDP at the time of sacrifice (day 20 post-exposure), thus offering a novel nutritional strategy of using SDP in feed to enhance the efficacy of a candidate ASFv vaccine and improve the health status of pigs under endemic ASFv conditions.

The studies demonstrate that nutrition supplemented with SDP and fed to vaccinated animals improved animal resilience to a subsequent pathogen exposure. It also maintained or improved vaccine efficacy. Dietary SDP favourably modulates the pro-inflammatory and anti-inflammatory cytokine profile in various mucosal tissues from animals with an activated immune system.

References available on request.

More:

Spray-dried plasma boosts vaccination effects, even with ASFv - Pig Progress

Study design

The VISION network has been described previously.15 We applied a test negative design to estimate vaccine effectiveness of mRNA vaccines using retrospectively collected data. We focused on mRNA vaccines because they comprise more than 95% of covid vaccines administered in the US.16 Separate analyses were done of patients who were admitted to hospital (hospital sample) and patients who received care in an emergency department or urgent care clinic (emergency department or urgent care sample).

The study population included adults (18 years) who received care for covid-like illness at a VISION network hospital or emergency department or urgent care center and had molecular testing for SARS-CoV-2 at least 14 days after vaccines became locally available for their age group (17 January to 3 May 2021). The last contact included in this study period occurred on 12 July 2022. We excluded individuals who received any vaccine other than the BNT162b2 or mRNA-1273 vaccine, individuals who received more than four doses of an mRNA vaccine before the index medical contact, individuals who received only one dose of an mRNA vaccine less than 14 days before the index contact or who had a third or fourth dose less than seven days before the index contact, individuals known to have a positive laboratory test result for a SARS-CoV-2 infection more than 14 days before the index contact, and individuals with a positive SARS-CoV-2 test result but no diagnoses or symptoms suggesting covid-19 illness.

Vaccination status was categorized by the number of doses received and the number of months between the most recent vaccine dose and the index contact date (referred to as time since vaccination). Patients were considered partially vaccinated if they received only one dose at least 14 days prior to the index contact date or had received a second dose less than 14 days previously. Patients with no record of vaccination before the index contact date were considered unvaccinated. Patients with three doses were those who received a third dose in a primary vaccination series (eg, among immunocompromised individuals) or a booster dose after a primary series of two doses. Aligning with recommendations for receipt of a fourth dose, we examined the effectiveness of four doses among adults aged 50 years or older and among immunocompromised adults of any age. Vaccination status was ascertained from immunization registries, electronic health records, and insurance claims.

The primary outcome was a positive or negative molecular SARS-CoV-2 result for a test done within 14 days before a medical contact to less than 72 h after among patients presenting with covid-like illness, as identified from ICD-9 and ICD-10 (international classification of diseases, ninth and 10th revision, respectively) diagnostic codes (supplemental methods; supplemental table S1). The index date for each contact was the earlier of either the contact date or the date of the closest SARS-CoV-2 molecular assay. An individual could be included as a case once in the emergency department or urgent care sample and once in the hospital sample. Individuals could be included as a control multiple times.

We used a test negative case-control design in which cases were patients with covid-like illness with laboratory confirmed covid-19 and controls were patients with covid-like illness and negative SARS-CoV-2 test results (controls could have had positive test results for other respiratory viruses such as influenza). We compared cases with controls in the hospital sample, and separately compared cases with controls in the emergency or urgent care sample. Cases were not individually matched to controls.

Conditional logistic regression was used to examine case-control status in relation to vaccination status categorized as vaccinated with four, three, or two doses, or partially vaccinated; unvaccinated individuals were used as the reference group. To examine waning of vaccine effectiveness, we categorized people who were vaccinated using time specific indicators defined by two month intervals of time since vaccination; unvaccinated individuals were used as the reference group. We exponentiated the regression coefficient of each vaccination status indicator to yield an odds ratio, subtracted the odds ratio from 1 to estimate vaccine effectiveness, and multiplied by 100 to scale vaccine effectiveness as a percentage. In several analyses, a sparse bimonthly interval for which the vaccine effectiveness estimate had a confidence interval wider than 50 percentage points was combined with the previous bimonthly interval to provide a more precise estimate of vaccine effectiveness (see supplemental methods). Vaccine effectiveness estimates (and confidence limits) were scaled to a range of 100% to 100%.17

Logistic regression models were conditioned by calendar week and geographical area such that we compared cases with controls tested during the same week in the same region (supplemental table S2). Covariates included in the models were those determined through bivariate analyses to be statistically significantly associated with both the outcome and vaccination status, as well as those specified a priori as established confounders, including age, race, ethnicity, presence of respiratory and non-respiratory comorbidities, immunocompromised status, and local viral circulation. Cubic splines were used for age, seven day average positivity of SARS-CoV-2 test in the area of the contact, and the propensity to be vaccinated; others were indicator variables. Propensity scores (supplemental methods) predicted vaccination (any versus none) based on demographics, comorbidities (supplemental table S3), and characteristics of the facility (supplemental table S4), and were derived independently for each period of variant dominance (supplemental table S5). Patients who were immunocompromised were identified by ICD-9 and ICD-10 diagnostic codes (supplemental methods).18 We conducted separate analyses for three periods based on when a variant accounted for 50% or more of sequenced isolates in each site: before delta was predominant, when delta was predominant, and when omicron was predominant (supplemental table S6). We assessed the magnitude of waning as the difference in vaccine effectiveness between patients who had recently been vaccinated (defined as less than two months) and patients at a specified level of time since vaccination (eg, four to five months from dose 3), and we examined waning by age (18-44 years, 45-64 years, 65 years), vaccine product, and immunocompromised status. Bootstrapping was used to estimate a 95% confidence interval around the difference between vaccine effectiveness at less than two months and vaccine effectiveness at four to five months.

We conducted several sensitivity analyses. First, we added to the study population patients with a known prior infection to assess the sensitivity of results to whether previously infected patients are included or excluded.. Second, we wanted to distinguish results between patients who had been admitted to hospital and patients who had been admitted to an emergency department or to urgent care. Therefore, we examined vaccine effectiveness in the emergency department or urgent care sample and omitted patients admitted to hospital within 30 days. Third, we investigated a negative control exposure19 by examining vaccine effectiveness in patients who received their first dose less than 14 days before the index date of contact. These patients were not expected to have substantial vaccine induced protection, and a vaccine effectiveness estimate substantially more than zero would be evidence of residual confounding.20

Analyses were conducted with SAS version 9.4 and R version 4.1.2. All confidence limits are 95% intervals. Confidence intervals excluding the null value were considered statistically significant.

Study participants contributed in important ways to this research by supplying the underlying data on which the study is based. It was not, however, feasible to involve them in the design, conduct, reporting, or dissemination of this study because the study was conducted under the CDCs covid-19 incident response structure and limited to analysis of retrospectively collected electronic data only, with no patient interaction.

Original post:

Waning of vaccine effectiveness against moderate and severe covid-19 among adults in the US from the VISION network: test negative, case-control study...

Immunisation coverage dipped in 2021 to the lowest level in decades. Worldwide, 18.2 million children received no vaccines at all. We probably arent yet aware of what the full ripple effects may be from the pandemics cataclysm, but devastating impacts are starting to be felt in outbreaks of diseases like polio, measles, and yellow fever. And because of the failure to meet coverage targets in 2021, 240,000 avoidable deaths will occur.

A new tool has been launched to help immunisation stakeholders understand the current status of vaccine systems. The Immunization Agenda 2030 (IA2030) scorecardis a publicly available interactive tool displaying data that enables immunisation managers and advocates at all levels global, regional, and country to monitor the status of immunisation systems. IA2030 is a global vision and strategy, co-created by countries and development partners and endorsed by the World Health Organization, to create a world where everyone, everywhere, at every age, fully benefits from vaccines to improve health and well-being.

Vaccine stakeholders can use the scorecard in several key ways:

Monitor progress toward immunisation targets. Countries, regions, and global stakeholders can visualise how each country and region contributes to meeting targets like averting 50 million deaths by 2030 and use the scorecard to guide decision-making and programme adaptations.

Understand the pandemics impact on immunisation systems. 2021 data shows that global DPT3 coverage fell to 81%, the lowest level since 2008.

Use visualisations to communicate about immunisation systems in high-impact presentations. Downloadable scorecard visualisations encompassing 18 different immunisation indicators at the global, regional, and country level help with communicating about vaccine investments and policy to decision-makers.

At the country level, compare performance between countries and against regional measures.Country pages provide at-a-glance data summarising the status of all IA2030 indicators, including which data is not yet being reported by a country.

Immunization Agenda 2030 Scorecard Dashboard shows Impact Goal-related setbacks in red.

IA2030 was co-created with stakeholders and first implemented during the pandemic, the worlds worst public health crisis in 100 years. COVID-related setbacks on immunisation systems in terms of declining vaccine coverage and other measures have been significant, but the pandemic also presents opportunity.

A silver lining of the past two years can be seen in how countries demonstrated the ability to rapidly introduce a new vaccine one given initially to adults, who can programmatically be harder to reach and track, as well as children. In 2021, 145 countries introduced COVID-19 vaccines. While global vaccine uptake is not yet equitable, in the first year of COVID-19 vaccination, an estimated 14.4 million lives have been saved.

Currently, data from a total of 18 indicators is available on the scorecard and presented at the global, regional and country level. Hundreds of country-to-country comparisons are enabled through country dashboards, and the scorecard also highlights where data are not yet available to encourage comprehensive reporting to assess the quality and functioning of immunisation systems at all levels.

Country-level data can be compared to regions or any other country.

Yet insights can be limited by current data reporting cycles. More rapid reporting of such data could provide opportunities for course correction and resource infusion in real-time. We look forward to this improving over time as data entry becomes timelier.

It is our hope that immunisation stakeholders will find the clear, easy-to-reference data on immunisation system performance at all levels valuable and that the tool will spur greater awareness of programmatic strengths and weaknesses. The scorecard is intended to encourage collaboration and rapid resource mobilisation with the aim of expanding vaccination to all, irrespective of where they live, enabling people across the world to fully benefit from vaccines for good health and well-being.

Alba Maria Ropero isSenior Lead for the Immunization Agenda 2030 at the World Health Organization

Dr Folake Olayinka is the USAID Immunization Technical Lead, STAR Fellowship at the Public Health Institute.

The scorecard is a collaborative effort led by USAID MOMENTUM Country and Global Leadership, in partnership with representatives from the IA2030 Advocacy and Communication Working Group and Monitoring & Evaluation Working Group, including specialists from the CDC, WHO, UNICEF, and UN Foundation. Strategic decisions were made by the IA2030 Secretariat and IA2030 Coordination Group.

Original post:

What's really happening with global vaccine access? - Gavi, the Vaccine Alliance

News Release

Tuesday, September 27, 2022

Large NIH-funded study included participants in North America and Europe.

A large international study has confirmed the findings of a previous U.S. study that linked COVID-19 vaccination with an average increase in menstrual cycle length of less than one day. The increase was not associated with any change in the number of days of menses (days of bleeding). Funded by the National Institutes of Health, the new study included data from nearly 20,000 people from Canada, the United Kingdom, the United States, Europe and other parts of the world who received any of nine different vaccines. For most study participants, the increase resolved in the cycle following vaccination.

The studys principal investigator was Alison Edelman, M.D., M.P.H., of Oregon Health & Science University in Portland. It appears in the BMJ Medicine.

These findings provide additional information for counseling women on what to expect after vaccination, said Diana Bianchi, M.D., director of NIHs Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). Changes following vaccination appear to be small, within the normal range of variation, and temporary.

NICHD and NIHs Office of Research on Womens Health funded the study, which was part of $1.67 million awarded to five institutions to explore potential links between COVID-19 vaccination and menstrual changes.

A change in cycle length of less than eight days is considered within the normal range of variation. Although small menstrual changes may not be meaningful to health care professionals and researchers, the study authors wrote, perceived changes in a bodily function linked to fertility may be alarming to those experiencing it and could contribute to vaccine hesitancy.

Researchers analyzed de-identified data from the fertility tracking app, Natural Cycles. Users of the app provided it information on their temperature and their menstrual cycles. They also had the option to consent to the use of their de-identified data for research. Worldwide rollout of COVID-19 vaccines allowed the study authors to expand on their original study of people in the United States. The study included data from participants throughout the world, but most were from the United Kingdom (32%), the United States and Canada (29%) and Europe (34%). In addition to the messenger RNA COVID-19 vaccines (Pfizer-BioNTech and Moderna), participants received COVID-19 vaccines made from engineered viruses (AstraZeneca, Covishield, Janssen/Johnson & Johnson and Sputnik), and inactivated viruses (Covaxin, Sinopharm, and Sinovac).

A total of 19,622 individuals participated. Of these, 14,936 were vaccinated and 4,686 were not. The researchers analyzed data on at least three consecutive cycles before vaccination and at least one cycle after. Data from at least four consecutive cycles were analyzed over a similar time interval for unvaccinated participants.

On average, vaccinated people experienced an increase of less than one day in each cycle in which they were vaccinated: a .71 day increase after the first dose and a .56 day increase after the second dose. Participants who received both doses in a single cycle had a 3.91 day increase in cycle length. After vaccination, cycle length had increased by only .02 days for individuals who received one dose per cycle, and .85 days for individuals who received two doses in one cycle, compared to participants who were not vaccinated. Changes in cycle length did not differ according to the type of vaccine received.

Of the total, 1,342 participants experienced a change in cycle length of eight or more days, comprising 6.2% of vaccinated individuals and 5.0% of unvaccinated individuals. Women who were younger and who had longer cycle length before vaccination were more likely to experience the increase.

The authors called for future studies on other aspects of vaccination-linked changes to menstrual cycles, such as unexpected vaginal bleeding and menstrual flow and pain. They also called for studies to determine the physical reasons why such changes might occur.

About the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): NICHD leads research and training to understand human development, improve reproductive health, enhance the lives of children and adolescents, and optimize abilities for all. For more information, visit https://www.nichd.nih.gov.

About the National Institutes of Health (NIH):NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.

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Study confirms link between COVID-19 vaccination and temporary increase in menstrual cycle length - National Institutes of Health (.gov)