U.S. vaccine makers say that the Food and Drug Administrations delay in designing this falls Covid-19 vaccines shouldnt push back the rollout of the shots, amid rapid shifts in the genetic makeup of the virus.
Vaccine makers Moderna and Novavax are hoping for an August rollout this year, earlier than last years late September debut of updated shots. Moderna CEO Stphane Bancel recently told Barrons that launching the shots in August instead of September could add three million doses to the market.
Sales of Pfizer , Moderna, and Novavax s shots fell far below expectations last year, setting off steep stock slides for all three of the companies. A better showing in the fall of 2024 could boost all three of the drugmakers.
The programs ran into a hiccup earlier this month, though, when the FDA delayed a May 16 meeting of its outside advisors to decide which strain of the virus the updated shots should address. As with the annual flu shots, Covid-19 shots are now tweaked each year to target the version of the virus currently circulating.
The virus that causes Covid-19 is a slippery target, and in recent weeks it has begun to change again. The FDA now plans to hold its strain selection meeting on June 5, a date thats still earlier than last years meeting, which was held June 15. In comments to Barrons on Monday, vaccine manufacturers seemed unfazed by the delay.
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A Moderna spokesperson said an August launch is still feasible, regardless of which strain the FDAs advisors choose. A Novavax spokesperson said that the later meeting date will not affect Novavaxs ability to deliver a Covid-19 vaccine this fall. A Pfizer spokesperson said that the company is aware of the date change, and that it is focused on working with the FDA.
The FDA, in a social media post on May 7, said it was delaying the meeting to allow more time to collect data to inform the committees recommendation. The postponement appeared to reflect the rapid changes in the makeup of the variant landscape in the U.S.
The strain that dominated in the U.S. since January of this year, known as JN.1, has begun to lose ground in recent weeks. The Centers for Disease Control and Prevention estimates that in the two-week period ending May 11, JN.1s prevalence had fallen to just 15%, as it has been surpassed by a number of its descendants. Chief among those descendants is the strain known as KP.2, which the CDC expects to have risen to 28.2% in the period ending May 11, quickly rising from just 1.4% in mid-March.
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The new variants replacing JN.1, including KP.2, share a handful of mutations scientists are calling FLiRT, which seem to give them an advantage over JN.1. CDC wastewater tracking shows that viral activity level for Covid-19 is currently minimal in the U.S.
Other global regulatory authorities have already made their decisions on which Covid strain to target. The World Health Organization said in late April said its advisory group recommended that new Covid-19 vaccines target JN.1. The European Medicines Agency made the same recommendation.
In an interview with Barrons in early May, Modernas Bancel said that his company had already begun manufacturing components for a shot targeting JN.1, but that the company was also preparing to make shots targeting one of the JN.1 descendants if necessary. We want to be a partner of the FDA from a public health standpoint, he said. They decide which strain goes into a vaccine and we will execute.
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Novavax, for its part, said at an earnings presentation May 10 that its also manufacturing a JN.1 vaccine, and that tests in non-human primates show that it induces an immune response against both JN.1 and the JN.1 descendant strains.
We have data which demonstrates good cross-reactivity between our JN.1 vaccine and KP.2, which is a JN.1 variant, the Novavax spokesperson said Monday. These data provide us confidence our vaccine has utility against the currently circulating strains.
Pfizer has not discussed its manufacturing plans for the fall Covid-19 shot.
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The question looming over the companies is how large the Covid-19 vaccine market will be this year, and whether an earlier launch will help with uptake. If the FDA and CDC can pull August off, I think the market should grow this year versus last year, Bancel told Barrons in early May.
Moderna, which so far is a pure play on Covid-19, saw its vaccine revenue fall 64% last year, to $6.7 billion, as demand for the vaccines evaporated.
Write to Josh Nathan-Kazis at josh.nathan-kazis@barrons.com
Pharmaceutical giant AstraZeneca recently admitted that its COVID-19 vaccine can cause a rare side effect of blood clotting. This acknowledgment came amidst legal action against the company that alleged severe harm and deaths linked to the vaccine, resulting in a rising concern among the people.
Dr Soumya Swaminathan former Chief Scientist of the World Health Organization (WHO), in an interaction with The Indian Express, gave her insights on several issues concerning COVID-19 vaccines. Among this, she also touched upon the subject of clotting due to the vaccines.
The clotting due to Covid is many times, perhaps even a hundred times, more than the clotting due to the vaccine, she said.
Addressing the public anxiety regarding the safety of COVID-19 vaccines, she expressed concern that this could undermine public confidence in vaccines. She emphasized the rigorous testing vaccines undergo for efficacy and safety. She highlighted that regulatory agencies conduct post-marketing surveillance or phase IV studies to detect rare side effects that could have been missed in clinical trials with smaller participant numbers.
She also elaborated that clinical trials for COVID-19 vaccines involved 30,000 to 40,000 participants, but rare side effects, like Thrombotic Thrombocytopenic Purpura (TTP), emerged when millions were vaccinated.
Every regulatory agency, including the WHO, looked at the safety profile again, assessed the risk-benefit ratio, and concluded that the benefits far outweighed the risks, she said
The rare side effects associated with COVID-19 vaccines like Covishield and Covaxin include pericarditis, myocarditis, and blood clotting.
Earlier this month, parents of 8 victims from Kerala, Mumbai, Coimbatore, Hyderabad, Bengaluru, and Kapurthala alleged that the deaths of their children were a result of the side effects of the Covishield vaccine. They intended to sue Punes Serum Institute of India and government officials responsible for the COVID-19 vaccine rollout.
Dr. Swaminathan discussed the difficulty of communicating scientific information to the public. She noted that vaccine hesitancy is not linked to education levels, as it is higher in well-educated regions like Western Europe and the US compared to India. Misunderstandings about scientists debates during the pandemic led to distrust, worsened by social media. She expressed that better public health communication and education are needed to counter misinformation.
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SINGAPORE Covid-19 antigen rapid test (ART) kits flew off the shelves at many pharmacies over the weekend after news broke that Singapore is facing a new wave.
Cases of Covid-19 have been rising in the last two weeks, a result of the Covid-19 sub-variants, which scientists have nicknamed FLiRT, drawing from the letters in the names of their mutations.
Globally, variant JN.1 and its sub-lineages, including KP.1 and KP.2, remain the predominant Covid-19 variants. The combined proportion of KP.1 and KP.2 currently accounts for more than two-thirds of the cases in Singapore.
As of May 3, the World Health Organisation has classified KP.2 as a variant under monitoring.
There are currently no indications, globally or locally, that KP.1 and KP.2 are more transmissible or cause more severe disease than other circulating variants.
Watsons has seen demand for Covid-19 test kits surge by more than 150 per cent in the past week, its Singapore managing director Irene Lausaid.
Our stores are well-stocked, and we have scheduled replenishments. We continuously seek collaborations with partners to promptly address any further increases in demand.
A Guardian spokeswoman said the chain has seen an increase in demand for Covid-19-related items, such as masks, test kits and cough and cold medicine, in line with the recent wave.
Despite this rise, there have been no instances of insufficient stock over the past two weeks. Guardian is proactively managing our inventory and working very closely with our suppliers to ensure that we maintain sufficient stock levels to meet our customers needs during this period, she said.
Heeding the Governments call for people to get an additional Covid-19 vaccine dose was Mr Senthil Nathan, 47, who was at the Sengkang joint testing and vaccination centre (JTVC) getting his fifth shot on May 20.
Mr Senthil, who works in the information technology industry, told The Straits Times he underwent a heart transplant more than 10 years ago and is on immunosuppressant drugs and has low immunity.
Study design, setting and study population
Participants of this cohort study were recruited from Sheikh Russel Gastroliver Institute & Hospital (SRGIH), a public sector health facility in Dhaka, Bangladesh when they visited the hospital to receive second dose of COVID-19 vaccines. Adults who received two doses of COVID-19 vaccines (OxfordAstraZeneca COVID19 vaccine or Covishield (viral vector-based vaccine), Pfizer-BioNTech (BNT162b2) (mRNA vaccine), Moderna (mRNA-1273) (mRNA vaccine) or Sinopharm (BBIBP-CorV) (inactivated whole virus vaccine)), were enrolled within 24weeks of receiving the second primary dose (visit 1) and followed-up at 4months (visit 2), 8months (visit 3) and 12months (visit 4). The inclusion criteria for participation were: (1) male or female adults (aged 18years and above), (2) able to understand and sign the informed consent form, (3) available and reachable by study staff for the entire period of the study; (4) agreeing to provide blood sample for the research study. The exclusion criteria were: (1) residence outside of Dhaka city; (2) suffering from long term severe illness such as cancer, chronic obstructive pulmonary disease (COPD) and chronic kidney disease (CKD).
Enrolment of participant started in September 2021 and ended in July 2022. Bangladesh received different types of COVID-19 vaccines at different time points either through COVAX or direct procurement, therefore availability of vaccinated individuals with any particular type of COVID-19 vaccine varied by time. Therefore, enrolment of vaccine groups varied by months. The Covishield was the first COVID-19 vaccine that was rolled out in Bangladesh and thus our first enrolled vaccine group was AstraZeneca vaccine. Administration of booster dose started in December 2021 in limited hospitals amongolder peoples (>60years of age) and age limit was gradually descended towards younger population. The participants of the AstraZaneca vaccine group received booster dose after almost 89months.
A structured questionnaire was utilized to collect data from each study participant at enrollment (visit 1, 24weeks after administration of 2nd primary dose) and each follow-up visit, i.e. at 4months (visit 2), 8months (visit 3) and 12months (visit 4) post second dose (Fig.1). Collected data included socio-demographic information (age, sex, education, migration background, ethnicity, marital status, household structure, occupation, and income), influenza-or COVID-like symptoms or presence of confirmed COVID-19 cases currently and in the past 6-months; co-morbidities (e.g. diabetes, hypertension, stroke, heart diseases and asthma). The vaccination type and administration dates were recorded. Information on receipt of booster dose was also collected during the follow-up phase. Height and weight were collected using stadiometer (Seca 217, Hamburg, Germany) and digital weighing scale (Camry-EB9063, China), respectively. Venous blood was collected at each visit in Lithium-heparin coated tubes (S-Monovette Plasma, Sarstedt AG & Co. KG, Nmbrecht, Germany), plasma was separated upon centrifugation, aliquoted, and stored at -80C until use.
The concentration of S-specific antibodies was determined in plasma by Elecsys Anti-SARS-CoV-2 S immunoassay kit (Roche DiagnosticsGmbH, Mannheim). This assay allowed quantitative determination of high affinity antibodies, predominantly IgG, but also IgA and IgM directed to the SARS-CoV-2 spike (S) protein receptor binding domain (RBD) in a double-antigen sandwich assay format on Cobas-e601 analyzer (Roche Diagnostics). According to the kit insert, the sensitivity of the Elecsys AntiSARSCoV2 S assay is 98.8%, clinical specificity is 99.98%, and the assay was found to have 92.3% positive agreement rate with a Vesicular Stomatitis Virus (VSV)-based pseudo-neutralization assay.
Nucleocapsid (N)-specific antibodies was determined in plasma by Elecsys Anti-SARS-CoV-2 immunoassay kit (Roche Diagnostics). The kit allows simultaneous detection of mature Nucleocapsid-specific IgM and IgG antibodies on an automated immunoassay analyzer (Cobas-e601, Roche Diagnostics). This is a qualitative assay that gives combined antibody titers of both IgM and IgG and does not differentiate between the two types. Based on the antibody cut-off index (COI), the serological response to SARS-CoV-2 is categorized as reactive (COI1.0, seropositive) and non-reactive (COI<1.0, seronegative). According to the kit insert, the Elecsys Anti-SARS-CoV-2 assay has 99.8% specificity and>99.5% sensitivity.
All participants vaccinated with viral vector-based vaccines (AstraZeneca) and mRNA vaccines (Pfizer and Moderna) were tested for N-antibodies to identify previous exposure to or infection with SARS-CoV-2. Participants immunized with Sinopharm vaccine (inactivated whole virus) were not tested for N antibodies as it is not possible to differentiate the N-antibodies induced by vaccination from those generated due to natural infection with SARS-CoV-2.
The study participants were defined as SARS-CoV-2 infected when tested positive by RT-PCR or showed COVID-like symptoms and concomitantly positive for N-antibodies. Individuals who did not exhibit COVID-like symptoms and were negative for N- antibodies or tested negative by RT-PCR were considered uninfected with SARS-CoV-2.
The authors affirm that all procedures involved in this research adhered to the ethical standards set by the pertinent national and institutional committees overseeing human experimentation, aligning with the Helsinki Declaration of 1975, revised in 2008. The study received approval from the institutional review board of icddr,b (PR-21069, dated 17 August 2021). Written informed consent was obtained from the participants.
The sample size was calculated based on the primary endpoint, i.e. to assess the persistence of SARS-CoV-2 S-specific antibody response following two primary doses of COVID-19 vaccines. A study by Shrotri M et al.12, demonstrated a decline of antibody titers by 19.7% from 0 to 21days to 2241days after administration of two doses of Pfizer vaccine. Based on this information, and considering statistical power of 80% and confidence interval of 95%, the estimated sample size was 64 per vaccine group. To reduce unknown bias due to different localities and socio demographic status, and unknown effects of COVID-19 vaccination, a design effect of 2 was added, which resulted in a sample size of 128. Considering 10% attrition rate, the final sample size was 140.8 (rounded to 141) per vaccine group and the total sample was 564. Despite rigorous efforts, we encountered difficulties in recruiting the target number of participants in the study. Within the duration of the study, administration of different COVID-19 vaccines was paused at different period. We were able to enroll only 452 participants, with the highest number in AstraZaneca vaccine group.
We showed basic demographic characteristics of the study participants, categorized by the respective vaccine types received (Pfizer, Moderna, AstraZeneca, and Sinopharm).
S-antibody data exhibited a right-skewed distribution in a histogram. To address this non-normal distribution, a natural log transformation was employed. To analyze the durability of S-antibody titers at different visits post-primary vaccination (primary endpoint), the participants across all vaccine groups were categorized into two groups: Group I consisted of individuals who remained uninfected with SARS-CoV-2 (defined above) and did not receive a 3rd dose of vaccine during the one-year study period. Group II included participants who got infected with SARS-CoV-2 (defined above), and did not receive a 3rd dose of vaccine during the study period. Furthermore, to assess the kinetics of S- antibody titers after the 3rd dose (secondary endpoint 1), the recipients were divided into 2 groups: Group III consisted of individuals who received the 3rd dose of vaccine between visit 2 and 3, and remained uninfected up to visit 4 (n=55); Group IV participants received the 3rd dose of vaccine between visits 2 and 3, but got infected with SARS-CoV-2 between visits 3 and 4 (n=12). Since the number of 3rd dose recipients was relatively small, the analysis in group III and IV was not stratified based on the type of COVID-19 vaccine received. Moreover, the AstraZeneca group was excluded from this analysis as this group received the 3rd dose between visit 3 and 4 (n=105), and could not be followed further after completion of 1-year follow-up to observe the durability of S-antibodies. To evaluate the mean differences in S-antibody titers between any two visits in each of the groups (groups I to IV), a multivariate regression model was employed. Repeated measure ANCOVA model was employed to examine the mean differences in S-antibody titers between multiple visits within a group. In order to determine the optimal model, age, sex, household income, occupation, body mass index (BMI), education, comorbidities, etc. were incorporated as covariates in the regression model. The effects of education and comorbidities was found minimal (<1%), thus, not included in the final regression model.
To assess the degree of protection from infection with SARS-CoV-2 (secondary endpoint 2) in mRNA and viral vector-based vaccine groups compared to inactivated vaccine as the reference group, Bayesian framework was adopted and Markov Chain Monte Carlo (MCMC) method was utilized to derive posterior distributions of model parameters. Furthermore, we applied model evaluation techniques and conducted sensitivity analyses to ensure the robustness of our results.
All statistical analyses were conducted using STATA (version 15) and Python (3.11), and GraphPad Prism was utilized for generating graphs. Significance was defined as a p-value of<0.05.
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A study conducted by researchers at the University of Warwick has unveiled crucial insights into the complex factors shaping vaccination decisions among pregnant women, particularly in the wake of the COVID-19 pandemic.
Pregnant women and their unborn babies face heightened risks of serious illness from infectious diseases such as Influenza (flu), Pertussis (whooping cough), and COVID-19. The research shows that despite the proven safety and efficacy of vaccinations during pregnancy, uptake remains alarmingly low, presenting a significant public health concern.
Despite the availability of free vaccinations for pregnant women in the U.K., of those who gave birth in England in October 2021, 29.4% had received two doses of the COVID-19 vaccine, compared to approximately 60.4% of the general population.
The study, titled "What factors influence the uptake of vaccinations amongst pregnant women following the Covid-19 pandemic: A qualitative study," published in Midwifery, interviewed pregnant women aged between 19 and 41 exploring their perceptions, experiences, and the factors influencing their decisions regarding vaccinations.
Dr. Jo Parsons from the University of Warwick who led the research said, "This research demonstrates the influence that the COVID-19 pandemic has had on pregnant women's views and uptake of recommended vaccinations and is further evident by the continuing decline in uptake since the pandemic.
"It is essential that pregnant women receive clear and consistent messaging, to allow them to make accurate and informed choices about vaccinating in pregnancy."
The findings are categorized into four main areas, each influencing pregnant women's vaccination decisions:
Commenting on the significance of the study, Dr. Jo Parsons said, "This research is vital to learn how pregnant women feel about accepting vaccinations following a pandemic, and how to address low uptake, to protect more pregnant women from largely preventable conditions. This research provides valuable insights and informs future interventions to be developed."
More information: Dr Jo Parsons et al, What factors influence the uptake of vaccinations amongst pregnant women following the Covid-19 pandemic: A qualitative study, Midwifery (2024). DOI: 10.1016/j.midw.2024.104021
(Precision Vaccinations News)
CSL and Arcturus Therapeutics today announce the journal Nature Communicationshas published results from an integrated phase 1/2/3a/3b study evaluating the safety, immunogenicity, and efficacy of ARCT-154, a novel self-amplifying (sa-mRNA) COVID-19 vaccine.
ARCT-154 is the world's first approved sa-mRNA COVID-19 vaccine for use in Japan.
The joint study's results demonstrate that two 5 g doses of ARCT-154, sa-mRNA vaccine, were well-tolerated, immunogenic, and provided significant protection against multiple strains of COVID-19.
The efficacy of ARCT-154 against severe COVID-19 was 100%in healthy persons aged 18-59 and more than 90%in persons at risk of severe consequences of the disease due to co-morbidities or older age.
"The results published inNature Communicationsdemonstrate the efficacy and tolerability of ARCT-154 and add to a growing body of evidence that our sa-mRNA vaccine has the potential to provide significant protection against the pervasive virus, reinforcing our promise to protect public health," said Jon Edelman, M.D., Senior Vice President, Vaccines Innovation Unit, CSL, in a press release on May 20, 2024.
Unlike standard mRNA vaccines, sa-mRNA vaccines instruct the body to make more mRNA and protein to boost the immune response.
CSL is a global biotechnology company with aportfolio of medicines and vaccines.
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COVID-19 antibodies are significantly reduced by 6 months post-vaccination among patients with immune-mediated inflammatory diseases, according to data published in The Journal of Rheumatology.
However, individuals with diseases such as rheumatoid arthritis and systemic lupus erythematosus continued to see positive impacts to immunogenicity with fourth and fifth doses of COVID-19 vaccines, the researchers wrote.
Currently, individuals with immune-mediated inflammatory diseases (IMIDs) may be unsure about the value of COVID vaccination beyond the primary series, study author Sasha Bernatsky, MD, PhD, of McGill University, in Montreal, told Healio. This is particularly concerning since immunosuppressant therapy may put individuals at higher risk for SARS-CoV-2 transmission.
On the other hand, social vaccine fatigue has caused many individuals to decline additional COVID boosters after the primary series, she added. Since COVID-19 infection is a potentially fatal and vaccine-preventable co-morbidity, it is vital that individuals with IMIDs have access to relevant information that will help them decide when to get their next COVID vaccination.
To examine how time since last vaccination impacts serologic responses to COVID-19 vaccination and infection in patients with IMIDs, Bernatsky and colleagues conducted a study of 1,823 adults (mean age, 53.2 years) with various relevant conditions. The cohort was recruited from eight cities across Canada beginning in early 2021. Dried blood spots or sera, as well as self-reported data, were collected at enrollment, then 2 to 4 weeks, and subsequently 3, 6 and 12 months, post-vaccination. Participants either collected dried blood spots at home and mailed them for analysis, or had sera analyzed at local centers, depending on their location.
Sasha Bernatsky
Samples underwent automated enzyme-linked immunosorbent assays to measure log-transformed anti-receptor-binding-domain (RBD) titers and anti-nucleocapsid IgG. The effects of each covariate on anti-RBD titers were expressed as exponentiated beta coefficients.
According to the researchers, log-transformed anti-RBD titers were positively associated with female sex, number of vaccine doses, self-reported COVID-19 infections between 2021 and 2023, and negatively associated with use of prednisone, anti-TNF agents and rituximab (Rituxan, Genentech) either the originator or biosimilars. Titers were also negatively associated with time since last vaccination, especially beyond 210 days (exponentiated coefficient = 0.88; 95% CI, 0.8-0.95).
Vaccine doses four and five were associated with positive effects on anti-RBD serology, the researchers wrote.
Our data suggest that these individuals should continue to consider additional doses when more than 6 months has elapsed since last vaccination or infection, Bernatsky and colleagues wrote.
Bernatsky said she was a bit surprised that rituximab demonstrated such strong effects (adjusted exponentiated coefficient = 0.23; 95% CI, 0.1-0.53) on lowering post-vaccination immune response, despite the cohort containing only 44 patients on rituximab.
However, this is a fairly robust finding across studies, so it is something we need to pay attention to, she told Healio.
These findings may help individuals personalize vaccination decisions, including consideration of additional vaccination when more than 6 months have elapsed since last COVID vaccination/infection, she added.
Bernatsky highlighted further research to be done in this area.
The intricate relationships between all these variables age, sex, race/ethnicity, number and timing of vaccination, type of vaccinations, past medical history and the details of medications received need to be carefully modelled for us to truly understand if we can personalize vaccine decisions, she said. That is, can we offer strategies tailored to each patients needs?
According to Bernatsky, the current analyses considered medication exposures only at the time the subject enrolled in our study.
We would like to undertake more detailed analyses of past medications and doses in order to identify those with higher or lower immune system responses to vaccination, she said. The ultimate goal is to prevent COVID-related infections, hospitalizations and deaths.
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Disclosures: This study was supported by funding from the Vaccine Surveillance Reference Group and COVID-19 Immunity Task Force of the Public Health Agency of Canada. The views expressed here do not necessarily represent the views of the Public Health Agency of Canada.
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As the saying goes "There is no such thing as normal" and this has been especially true after the pandemic.
Before the emergence of the omicron COVID-19 variant, countries like the U.K. had high vaccination coverage along with widespread exposure to COVID-19 in the population.
This combination of vaccine and infection-derived immunity is termed hybrid immunity and is different to vaccine immunity or infection immunity alone.
In contrast, other countries, including Australia, New Zealand and those in the Western Pacific, had a very different pandemic experience. These countries and regions had low prior exposure and differing levels of vaccination.
The widespread waves of COVID-19 that followed the emergence of the omicron variant in late 2021 completely changed the immune landscape.
Omicron sharply increased COVID-19 exposures across the world, including in the Western Pacific Region which previously had low exposure.
Now, there is a complex global situation where populations in different countries have unique hybrid immunity landscapes, born from a wide range of vaccination history and exposure history combinations.
In 2023, we needed to consider what hybrid immunity meant for booster vaccinations. And what different types of hybrid immunity meant for future vaccination strategies.
Because while countries were "returning to normal," SARS-CoV-2 hadn't gone away. We needed a systematic way to make population-level recommendations and support government decision-making on a global scale.
We gain hybrid immunity from a combination of COVID-19 vaccinations and past infections. When a population goes through various COVID-19 waves and cycles of vaccination, the population acquires a complex hybrid immune landscapeand this is the current state in countries around the world.
Hybrid immunity can prevent future infection and reduce the severity of outcomes. We were particularly interested in what this means for future waves of COVID-19 and the implications on future vaccine strategies.
Given competing health priorities and resource constraints, governments and policymakers need to assess their future vaccination policies. After all, if a population already has high immunity derived from infection, are vaccinations still required?
Our modeling helps us answer this question, finding that yes, vaccinations are still important on the population level, but they will likely be used in a different way in future.
Our model is an "agent-based model," where we simulate thousands of "individuals," each with their own vaccination and infection histories.
With a focus on the Western Pacific Region, we configured the model to a range of exemplar populations in the region, accounting for prior immunity and vaccination coverage (ranging from high to low), and population age structure (older versus younger age demographics).
Then, by running the model "into the future," under various scenarios regarding COVID-19 variants and vaccine coverage, we tested what could happen, given different historical settings (hybrid-immunity levels) and the future emergence of new variants.
The strongest benefit of COVID-19 vaccines is their protection against severe outcomes, including hospitalization. In contrast, they have limited efficacy against transmission between infected and non-infected people.
Our results suggest that populations with low vaccination coverage and high past infection rates should still consider vaccination if public health measures are not enforced or social mixing is not reduced, with particular emphasis on protecting those at higher risk, such as older age groups.
Modeling can help us understand ongoing COVID-19 waves, including the likely impact of responsive vaccine interventions, and how vaccinations will continue to play a key role in keeping people healthy and safe.
Using this work as a springboard, we extended it in response to a request for data modeling from the World Health Organization (WHO) Strategic Advisory Group of Experts on Immunization (SAGE) Working Group on COVID-19.
We evaluated the cost-effectiveness of vaccination strategies across a range of settings considering (largely) unvaccinated low- and middle-income countries (LMICs) and well-vaccinated countries.
These results fed into the global policy decisions through the WHO's SAGE Group and their Immunization and Vaccine-related Implementation Research Advisory Committee (IVIR-AC).
In particular, our modeling informed WHO's revised (March 2023) recommendations for COVID-19 booster vaccination to achieve equitable health outcomes.
COVID-19 continues to circulate in the global population. However, competing health priorities and resource constraints mean governments and policymakers must carefully consider if, when, and who to vaccinate.
Complex and diverse immune landscapes and global needs make it difficult to guide broad policy on vaccine decision-making.
Our flexible framework can consider different country contexts by inputting different age distributions, vaccination schedules, contact matrices and other key parameters to help determine the relative benefits of potential vaccine programs in different populations.
This information helps support individual countries in deciding what part vaccines will play in protecting populations against emerging variants of concern.
Vaccines are vital to global health, saving millions of lives each year. The COVID-19 pandemic underscored their importance, with more than 20 million lives saved in the first year of vaccine deployment alone. This achievement was fueled by an unprecedented acceleration in innovation, with multiple COVID-19 vaccine candidates developed and launched within roughly one year, a process that has historically taken a decade on average.
This level of activity was dramatically different from what we saw in our 2019 analysis, which revealed signs that the vaccine innovation engine had begun to sputter. While the two decades preceding the pandemic saw strong growth in the vaccine industrywith pipelines doubling and annual growth rates of 12 to 15 percentwe identified four indicators of stagnation in 2019: slowing revenue growth (only 5 percent across the industry over the previous five years), a flattening development pipeline, higher attrition rates for vaccines compared with other biologics, and limited progress targeting disease areas of high unmet need, particularly those endemic to low- and middle-income countries (LMICs).
At that time, we highlighted opportunities to reinvigorate vaccine innovation across six major vaccine archetypes (Exhibit 1) by addressing commercial and technical obstacles and advocated for a comprehensive and shared approach among the relevant stakeholders, including manufacturers, governments, academia, research centers, and the private sector. Some of these strategies proved instrumental to the rapid development of the COVID-19 vaccines.
Now, roughly three years after the surge of innovation spurred by the pandemic, the vaccine industry faces another critical juncture. Despite accelerated vaccine innovation for certain diseases, progress remains uneven, and significant unmet needs persist. This article explores how the pandemic transformed the business case for vaccines. It proposes five actions the vaccine ecosystem can take to harness the pandemic-driven momentum to accelerate vaccine innovation more broadly and to tackle global health challenges more effectively.
The rapid development of COVID-19 vaccines was propelled by multiple factors, including enhanced funding, operational efficiency, technological advancements, and regulatory flexibility. The COVID-19 innovation model has spurred advancements in other areas, particularly in respiratory diseases, which saw ten launches in the United States alone from 2020 to 2023 (up from three between 2016 and 2019). In the past several years, multiple vaccines targeting diseases that primarily affect LMICs, such as dengue and chikungunya, have also been approved by the US Food and Drug Administration (FDA). The vaccine development pipeline has also seen a rise in Phase III candidates (Exhibit 2), which include two meningitis vaccines, a possible human cytomegalovirus (CMV) vaccine, and a promising vaccine against invasive pneumococcal disease in adults.
The overall vaccine development timeline is also compressing (Exhibit 3). Although not as rapid as the unprecedented COVID-19 timeline, which was roughly one year, respiratory syncytial virus (RSV) vaccines have been developed within a three- to five-year time frame (the start of clinical development through regulatory approval), a pace significantly quicker than historical norms. Other vaccine types that are also moving relatively quickly through the clinical phases include Modernas messenger ribonucleic acid (mRNA) combination vaccine candidate for RSV and seasonal influenza, which is on a three- to four-year projected development timeline.
Despite these advances, progress has been uneven across different vaccine archetypes (Exhibit 4). Multiple vaccines were launched in recent years that target residual unmet needs (archetype two) such as malaria, pneumonia, and meningitis, with additional late-stage candidates in the pipeline. However, few vaccine candidates for neglected diseases (archetype five) have progressed to late-stage clinical development. Vaccines for this disease archetype face high levels of commercial uncertainty as well as technical complexity, including difficulty in generating protective immunity.
Vaccines targeting persisting global threats (archetype three), including HIV and the EpsteinBarr virus, face technical challenges in identifying appropriate antigens and generating sufficient immune responses, especially for pathogens with complex life cycles. And although concerns about hospital-acquired antibiotic-resistant infections have piqued interest in nosocomial-associated threats (archetype six), efforts to develop vaccines for them have returned mixed results.
Some projects, such as an E. coli vaccine candidate, have moved into Phase III trials; others, including several C. difficile vaccine attempts, have not been successful. These initiatives also face commercial and logistical challenges, including uncertainties about how to identify the target demographic for vaccination and the optimal timing for vaccine administration.
Addressing disparities and accelerating vaccine development for these unmet needs remain crucial in the ongoing fight against infectious diseases. Overcoming technical challenges and streamlining the development process will be essential to closing the gaps in the vaccine development pipeline and ensuring worldwide equitable access to lifesaving vaccines.
The response to the COVID-19 pandemic strengthened the vaccine business case and led to a remarkable 30 percent increase in vaccine candidates over the past five years.
The development of vaccines targeting infectious diseases has historically been hindered by an unfavorable business case characterized by high capital costs, long regulatory timelines, increased opportunity costs, technical complexity, and commercial uncertainty. However, the response to the COVID-19 pandemic strengthened the vaccine business case and led to a remarkable 30 percent increase in vaccine candidates over the past five years (Exhibit 5). These changes to the business caseswhich demonstrated what is possible when the right stakeholders work together to accelerate innovationincluded the following:
Economic R&D and manufacturing incentives. Unprecedented levels of funding were also appropriated for vaccine R&D, including more than $2 billion each from the US federal government and the global PPP Coalition for Epidemic Preparedness Innovations (CEPI). Canada, Germany, and other public- and private-sector stakeholders worldwide also directly invested in expanding manufacturing capacity to reduce the financial risk of scaling up vaccine production.
Despite a substantial increase in public funding, it is important to note that private funding for infectious disease vaccine R&D still lags behind funding in other areas, with only 3.4 percent of the total venture capital raised for biopharmaceutical companies during the past ten years going to companies with infectious-disease-vaccine programs, compared with 38 percent for oncology programs.
Although the speed, magnitude, and cohesiveness of these responses are far more sustainable during a pandemic than in a steady state (noncrisis-related) vaccine development environment, they have given the industry a model for accelerating innovation.
The vaccine ecosystem now faces another inflection point: Will it revert to a state that is more susceptible to a challenging business case, or will it draw lessons from the pandemic and sustain or even accelerate the vaccine innovation momentum it ignited? The five actions detailed below (and outlined in Exhibit 6) aim to enhance the vaccine development landscape by addressing key drivers such as investment requirements, regulatory hurdles, and market uncertainties.
The COVID-19 pandemic showed how alliances among companies, not for profits, academia, and governments can accelerate R&D and manufacturing. Several of the most quickly approved COVID-19 vaccines represented R&D partnerships among research institutes, academia, and industry, including the National Institutes of Health/Moderna and the University of Oxford/AstraZeneca collaborations.
In addition, broader collaborations such as the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) partnership brought together US federal agencies, innovators, academia, and others to develop a research strategy to accelerate the development of COVID-19 vaccines and therapeutics and coordinate clinical trials. Vaccine manufacturing partnerships and networks also grew significantly during the pandemicmore than 70 percent of the 374 manufacturing and supply chain announcements involved a collaboration among multiple stakeholders.
There are signs that these types of partnerships will continue to grow in the coming years, particularly partnerships focused on rapid production of vaccines for future pandemics, such as the one CEPI is building in the Global South. Maintaining these partnerships beyond the pandemic context could lower capital costs and speed up production. However, new collaboration models are required to ensure rapid technology transfer with minimal risk and resource demands.
The scale of COVID-19 funding is unrealistic for steady-state vaccine development and potentially even unnecessary for more commercially attractive blockbuster vaccines. However, targeted funding commitments can reduce investment risks and promote ongoing innovation, particularly for vaccine candidates aimed at diseases prevalent in LMICs. The ones set up by the Biomedical Advanced Research and Development Authority (BARDA) and Gavi could inspire the design of future funding mechanisms.
Even without the scale of COVID-19 investment, global funders and international institutions can boost the commercial appeal of vaccine development if they offer clear innovation funding incentives. For example, Gavis recently established African Vaccine Manufacturing Accelerator has committed to making $1 billion available to manufacturers at critical moments in the development process to offset their start-up costs and create demand certainty for vaccines that may be needed to prevent future pandemics.
The pandemic demonstrated the potential for high vaccination rates among the adult population. Sustaining such levels will require coordinated efforts across the healthcare ecosystem to improve vaccine access, engage populations that are more vulnerable to certain diseases, and innovate delivery methods.
COVID-19 vaccination rates among adults who received first doses were historically high during the pandemic; conversely, the vaccination rates for subsequent booster doses have been in line with and, in some cases, lower than the rates for other adult vaccines. As of March 2024, fewer than 25 percent of eligible adults in the United States had received an updated 202324 COVID-19 vaccine since September 2023. Despite the US Centers for Disease Control and Preventions recommended immunization schedule for adults, adult immunization rates are consistently lower than those of children and vary significantly by geography and demography. Each year for the past decade, only 30 to 50 percent of mid-adults (18 to 64 years old) have gotten a seasonal influenza vaccine.
To help ensure the public health benefits and stabilize the commercial demand, the public sector, vaccine manufacturers, retail pharmacies, and other stakeholders could take the following coordinated and complementary actions:
The COVID-19 pandemic highlighted the importance of fungible capacity to reduce bottlenecks to widespread vaccine availability. Transitioning toward flexible, multiproduct manufacturing can help ensure readiness for future pandemics and streamline production processes.
The historical model, in which most large vaccine manufacturing facilities specialize in a single product, may no longer be fully fit for purpose, particularly given the need to prepare for future pandemics. One example of fungible manufacturing is at-scale systems that either allow the production of multiple vaccine types on the same platform or can produce the same vaccine on various platforms. Such flexible technology platforms will be critical to avoid building excess capacity. They will also likely be most crucial in the shorter term, particularly in the context of pandemic preparedness.
However, the expense of flexible capacity will require new incentives and significant investment on behalf of funders and manufacturers. We are seeing some promising signs of innovation. For example, Sanofis Evolutive Vaccine Facilities platform is designed around a central unit housing several fully digital production modules, making it possible to produce three to four vaccines simultaneously. This modularity can make it possible to prioritize the production of a specific vaccine more quickly.
The COVID-19 pandemic highlighted the benefits of cooperation, communication, and collaboration between innovators and regulators, which could be integrated into regular practice for other diseases. For example, at a 2023 US Senate hearing, the FDA commissioner discussed a program from the Center for Biologics Evaluation and Research (CBER) devoted to emerging pathogens. The program would, among other things, expedite reviews, provide guidance to developers, leverage real-world data for product assessment, and support advanced manufacturing.
Initiatives launched before the pandemic can offer inspiration for the design of new vaccine-focused mechanisms. For example, the European Unions PRIME initiative, launched in 2016, offers enhanced support for the development of therapies addressing unmet needs, including early contact with the European Medicines Agency and expedited scientific advice during development. The FDAs Oncology Center of Excellence Real-Time Oncology Review (RTOR) program, launched in 2018, enables faster reviews by allowing submission of top-line efficacy and safety results for drug candidates likely to demonstrate substantial improvements or candidates with straightforward study designs. This allows for earlier identification of issues that may arise during development and helps regulators and innovators align on trial design.
Global regulatory cooperation can also accelerate vaccine innovation and streamline administrative processes. During the pandemic, forums such as the International Coalition of Medicines Regulatory Authorities formed COVID-19 working groups that rapidly accelerated vaccine development by establishing governing protocols, agreeing on approaches to adapt vaccines to address variants, and improving regulatory agility. Also, the WHO-backed African Vaccine Regulatory Forum introduced an emergency joint review process that led to an accelerated review turnaround. Working groups for other diseases could promote consistent standards and requirements, encouraging innovation and bolstering clinical trial efficiencies. Expanding regulatory measures such as accepting electronic files and conducting virtual inspections could also promote vaccine innovation.
In the meantime, innovators can consider assessing and improving the level of their submission excellence, or their ability to quickly prepare high-quality regulatory submissions, which can help boost the odds of first-cycle approval.
The COVID-19 pandemic ignited a revolution in vaccine development. Unprecedented speed and scale brought lifesaving vaccines to the world in record time. However, without concerted effort, the urgency that fueled innovation during the crisis could easily dissipate. The five actions outlined in this article provide a road map for sustaining the innovation surge and accelerating the development of lifesaving vaccines for the worlds most pressing health challenges. With collective action and unwavering commitment, stakeholders in the vaccine ecosystem can harness the lessons of the pandemic to spur transformative change and help secure a healthier future for all.
