High Vaccine Efficacy Research Articles

A two-strain COVID-19 co-infection model with strain 1 vaccination

COVID-19 has caused substantial morbidity and mortality worldwide. Previous models of strain 1 vaccination with re-infection when vaccinated, as well as infection with strain 2 did not consider co-infected classes. To fill this gap, a two co-circulating COVID-19 strains model with strain 1 vaccination, and co-infected is formulated and theoretically analyzed. Sufficient conditions for the stability of the disease-free equilibrium and single-strain 1 and -strain 2 endemic equilibria are obtained. Results show as expected that (1) co-infected classes play a role in the transmission dynamics of the disease (2) a high efficacy vaccine could effectively help mitigate the spread of co-infection with both strain 1 and 2 compared to the low-efficacy vaccine. Sensitivity analysis reveals that the main drivers of the effective reproduction number Re are primarily the effective contact rate for strain 2 (β2), the strain 2 recovery rate (τ2), and the vaccine efficacy or infection reduction due to the vaccine (η). Thus, implementing intervention measures to mitigate the spread of COVID-19 should not ignore the co-infected individuals who can potentially spread both strains of the disease.

COVID-19 vaccination in patients with multiple sclerosis: what you need to know - a review.

The appearance of severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) initiated the COVID-19 pandemic, resulting in millions of confirmed cases and numerous fatalities. In response, rapid vaccine development efforts were launched to mitigate the pandemic's impact. Despite the high efficacy of COVID-19 vaccines, they are also associated with several common side effects/complications, some of them specific to the multiple sclerosis population. Our goal is to review various types of COVID-19 vaccines, assessing their efficacy, adverse events, their association with an MS relapse following vaccination, and the influence of disease modifying therapies (DMTs) on vaccines' efficacy. The review was based on a database search that included PubMed/Medline, Embase, Scopus, and the Web of Science conducted from January 2020 to July 2024 using the following MeSH terms: MS, COVID-19, COVID-19 vaccination, vaccine side effects, and vaccine hesitancy. Receiving any type of COVID-19 vaccine is a safer and more reliable approach to building immunity compared to becoming infected with the virus. Complications tend to be mild to moderate, occasionally severe. DMTs could affect the humoral response to the COVID-19 vaccine. Among all DMTs, a notable reduction in the humoral response has been observed in patients who received anti-CD20 and sphingosine-1-phosphate (S1P) receptor modulator drugs after their COVID-19 vaccination. Despite certain drawbacks, the benefits of the COVID-19 vaccine significantly outweigh the associated risks, making it a recommended course of action for people with multiple sclerosis (pwMS). However, physicians need to be mindful of potential complications especially in patients undergoing anti CD20 and manage them appropriately.

Epidemiology and genetic characterization of influenza viruses circulating in Bhutan in 2022.

Influenza (Flu) causes considerable morbidity and mortality globally, and in Bhutan, Flu viruses are a leading cause of acute respiratory infection and cause outbreaks during Flu seasons. In this study, we aim to analyze the epidemiology and the genetic characterization of Flu viruses circulated in Bhutan in 2022. Respiratory specimens were collected from patients who meet the case definition for influenza-like illness (ILI) and severe acute respiratory infection (SARI) from sentinel sites. Specimens were tested for Flu and SARS-CoV-2 viruses by RT-PCR using the Multiplex Assay. Selected positive specimens were utilized for Flu viral genome sequencing by next-generation sequencing. Descriptive analysis was performed on patient demographics to see the proportion of Flu-associated ILI and SARI. All data were analyzed using Epi Info7 and QGIS 3.16 software. A weekly average of 16.2 ILI cases per 1000 outpatient visits and 18 SARI cases per 1000 admitted cases were reported in 2022. The median age among ILI was 12 years (IQR: 5-28) and SARI was 6.2 (IQR: 2.5-15) years. Flu A(H3N2) (70.2%) subtype was the most predominant circulating strain. Flu A(H1N1)pdm09 and Flu B viruses belonged to subclades that were mismatched to the vaccine strains recommended for the 2021-2022 season but matched the vaccine strain for the 2022-2023 season with vaccine efficacy 85.14% and 88.07% respectively. Flu A(H3N2) virus belonged to two subclades which differed from the vaccine strains recommended in both the 2021-2022 and 2022-2023 seasons with vaccine efficacy 68.28%. Flu virus positivity rates were substantially elevated during the Flu season in 2022 compared to 2021. Flu A(H3N2) subtype was the most predominant circulating strain in the country and globally. Genetic characterization of the Flu viruses in Bhutan showed a close relatedness of high vaccine efficacy with the vaccine strain that WHO recommended for the 2022-23 season.

The transmission dynamics of an infectious disease model in fractional derivative with vaccination under real data

The resurgence of monkeypox causes considerable healthcare risks needing efficient immunization programs. This work investigates the monkeypox disease dynamics in the UK, focusing on the impact of vaccination under real data. The key difficulty is to correctly predict the spread of the disease and evaluate the success of immunization efforts. We construct a mathematical model for monkeypox infection and extend it to the fractional case considering the Caputo derivative. The analysis ensures the positivity, boundedness, and uniqueness of the solution for the non-integer system. We conduct a local asymptotical stability analysis (LAS) at the disease-free equilibrium (DFE) D0, showing the result for R0<1. Additionally, we demonstrate the existence of multiple endemic equilibria and provide conditions for backward bifurcation, which are illustrated graphically. Using real case data from the UK, we estimate model parameters via the nonlinear least square method. Our results show that, without vaccination, R2≈0.8, whereas vaccination reduces it to R2v=0.48. We perform sensitivity analysis to identify key parameters influencing disease elimination, presenting the outcomes through graphs. To solve numerically the fractional model, we outline a numerical scheme and provide detailed results under various parameter assumptions. Our findings suggest that high vaccine efficacy, a low waning rate of the vaccines, and increased vaccination of the infected people can significantly reduce the future cases of monkeypox in the UK. The present study offers a comprehensive framework for monkeypox dynamics and informs public health strategies for effective disease control and prevention.

Protection of K18-hACE2 Mice against SARS-CoV-2 Challenge by a Capsid Virus-like Particle-Based Vaccine.

The SARS-CoV-2 pandemic and the emergence of novel virus variants have had a dramatic impact on public health and the world economy, underscoring the need for detailed studies that explore the high efficacy of additional vaccines in animal models. In this study, we confirm the pathogenicity of the SARS-CoV-2/Leiden_008 isolate (GenBank accession number MT705206.1) in K18-hACE2 transgenic mice. Using this isolate, we show that a vaccine consisting of capsid virus-like particles (cVLPs) displaying the receptor-binding domain (RBD) of SARS-CoV-2 (Wuhan strain) induces strong neutralizing antibody responses and sterilizing immunity in K18-hACE2 mice. Furthermore, we demonstrate that vaccination with the RBD-cVLP vaccine protects mice from both a lethal infection and symptomatic disease. Our data also indicate that immunization significantly reduces inflammation and lung pathology associated with severe disease in mice. Additionally, we show that the survival of naïve animals significantly increases when sera from animals vaccinated with RBD-cVLP are passively transferred, prior to a lethal virus dose. Finally, the RBD-cVLP vaccine has a similar antigen composition to the clinical ABNCOV2 vaccine, which has shown non-inferiority to the Comirnaty mRNA vaccine in phase I-III trials. Therefore, our study provides evidence that this vaccine design is highly immunogenic and confers full protection against severe disease in mice.

Sequencing Analysis of the N gene of Canine Distemper Virus from Infected Dogs in Baghdad City

The primary aim of this study was to analyze the nucleocapsid (N) gene of the Canine Distemper Virus (CDV) in infected canines within Baghdad, Iraq. A total of 50 samples, encompassing nasal swabs and fecal specimens, were obtained from canines of various ages and breeds. Utilizing a Rapid Test, nine of 50 samples tested positive for CDV. Subsequent to this, the RNA from the positively tested samples was extracted and subjected to Reverse ‎Transcription-‎Polymerase Chain Reaction (RT-PCR) for cDNA synthesis. The synthesized ‎cDNA was further amplified through conventional PCR targeting the N gene. Six of these amplified products were submitted to Macrogen, South Korea, for sequencing. Sequence analysis revealed multiple silent and missense point mutations within the N gene. Phylogenetic analysis indicated a 99% similarity of the N gene in the Iraqi strains to a known strain from the USA. Overall, this study identifies point mutations in the N gene of CDV in infected canines in Iraq and establishes that ‎the circulating strain exhibits high genetic resemblance to a USA strain. Therefore, it is imperative to formulate and implement high-efficacy vaccines and comprehensive control ‎strategies‎. This represents the first study in Iraq to focus on the N gene ‎analysis of CDV in infected dogs.

#2434 Literature review on the burden of herpes zoster in patients with kidney disease—a need for earlier prevention

Abstract Background and Aims Kidney disease (KD), including end stage renal disease (ESRD), is a global health problem. Both are associated with impaired immune systems, which can lead to infections. Complications such as cardiovascular disease and various infections are leading causes of morbidity and mortality in KD patients. Notably, patients with KD have an increased risk of herpes zoster (HZ). While the link between ESRD and renal transplant with increased HZ risk is understood, knowledge gaps regarding the burden of HZ across the KD spectrum still exist. This review aims to describe the risk and impact of HZ across the KD spectrum in order to guide preventive care strategies for patients with renal diseases. Method A structured literature review was conducted in PubMed using a combination of keywords and Medical Subject Heading (MeSH) terms to identify studies related to HZ risk in adult KD patients aged ≥18 years published in the English language between 01/11/2003–31/10/2023. Data extracted from published studies included the burden of HZ infection in patients with KD (risk of HZ and related complications), impact of HZ on underlying KD, and the efficacy/effectiveness of HZ vaccines among patients with KD. Results A total of 47 studies were identified (Randomized controlled trials [RCT] = 2; observational studies = 45) in this review (Fig. 1). Included studies presented evidence from regions in Europe (n = 18), Asia (n = 17), North America (n = 7), South America (n = 1), multinational (n = 2) and Australia (n = 1); country not reported in one study. Evidence from observational studies (n = 37) reported a high risk of HZ infection and related complications, such as disseminated HZ, and recurrent HZ across the KD spectrum, including chronic KD, polycystic KD, hemodialysis, peritoneal dialysis and kidney transplant patients. Infection with HZ was reported to accelerate KD progression and increased the risk of ESRD and cardiovascular events. In general, for ESRD patients with an inpatient HZ diagnosis, mortality increased with age, followed by malnutrition and bacteremia/septicemia. Studies reporting vaccine efficacy (n = 2) and effectiveness results (n = 8) suggest that HZ vaccination was associated with a reduced risk of HZ when compared to unvaccinated individuals. Furthermore, the recombinant zoster vaccine (RZV) was found to be immunogenic in kidney transplant recipients, with immunogenicity persisting through 12 months post-vaccination. An RCT post-hoc analysis showed high vaccine efficacy in patients aged ≥50 years with medical conditions at enrollment, including KD, which was consistent with the overall population. A favorable benefit-risk profile was reported in randomized and observational studies. Studies evaluating the effectiveness of the zoster live-attenuated vaccine (ZVL) found a lower risk of HZ in patients with ESRD immunized against HZ compared to unvaccinated individuals. In many countries, vaccination guidelines specifically recommended immunization of people with KD to protect against HZ. However, ZVL is contraindicated for immunocompromised (e.g. kidney transplant) patients. Conclusion Findings indicate that HZ has a significant HZ burden across the KD spectrum, which may negatively impact renal disease progression. With effective vaccines offering durable protection against HZ and its complications, the immunization of renal patients at earlier stages could enhance healthcare management and patient outcomes.

The Immunogenicity of Monovalent Oral Poliovirus Vaccine Type 1 (mOPV1) and Inactivated Poliovirus Vaccine (IPV) in the EPI Schedule of India.

In 2016, the Global Polio Eradication Initiative (GPEI) recommended the cessation of using type 2 oral poliovirus vaccine (OPV) and OPV, with countries having to switch from the trivalent to bivalent OPV (bOPV) with the addition of inactivated poliovirus vaccine (IPV) in their routine immunization schedule. The current GPEI strategy 2022-2026 includes a bOPV cessation plan and a switch to IPV alone or a combination of vaccine schedules in the future. The focus of our study was to evaluate the immunogenicity of monovalent OPV type 1 (mOPV1) with IPV and IPV-only schedules. This was a three-arm, multi-center randomized-controlled trial conducted in 2016-2017 in India. Participants, at birth, were randomly assigned to the bOPV-IPV (Arm A) or mOPV1-IPV (Arm B) or IPV (Arm C) schedules. Serum specimens collected at birth and at 14, 18, and 22 weeks old were analyzed with a standard microneutralization assay for all the three poliovirus serotypes. The results of 598 participants were analyzed. The type 1 cumulative seroconversion rates four weeks after the completion of the schedule at 18 weeks were 99.5% (97.0-99.9), 100.0% (97.9-100.0), and 96.0% (92.0-98.1) in Arms A (4bOPV + IPV), B (4mOPV1 + IPV), and C (3IPV), respectively. Type 2 and type 3 seroconversions at 18 weeks were 80.0% (73.7-85.1), 76.9% (70.3-82.4); 93.2% (88.5-96.1), 100.0% (98.0-100.0); and 81.9% (75.6-86.8), 99.4% (96.9-99.9), respectively, in the three arms. This study shows the high efficacy of different polio vaccines for serotype 1 in all three schedules. The type 1 seroconversion rate of mOPV1 is non-inferior to bOPV. All the vaccines provide high type-specific immunogenicity. The program can adopt the use of different vaccines or schedules depending on the epidemiology from time to time.

Review of mathematical models of Neisseria gonorrhoeae vaccine impact: Implications for vaccine development

An effective prophylactic vaccine for prevention of Neisseria gonorrhoeae infection would have a major impact on sexual and reproductive health worldwide. Interest in developing gonorrhoea vaccines is growing due to the reported high rates of N. gonorrhoeae infections globally, and the threat of antimicrobial resistance. Several gonorrhoea vaccine candidates are currently under evaluation and various mathematical models have been used to assess the potential population-level impact a gonorrhoea vaccine may have once available. Here we review key aspects of gonorrhoea vaccine mathematical modelling studies, including model structures, populations considered, and assumptions used as well as vaccine characteristics and implementation scenarios investigated. The predicted vaccine impact varied between studies, ranging from as little as ∼17 % reduction in N. gonorrhoeae prevalence after 30 years up to 100 % reduction after 5 years. However, all studies predicted that even a partially effective gonorrhoea vaccine could have a substantial impact in reducing N. gonorrhoeae prevalence or incidence, particularly when high coverage is achieved within either important risk groups or the overall sexually active population. As expected, higher vaccine efficacy against acquisition of N. gonorrhoeae and longer duration of protection were linked to greater reductions in infections. A vaccine that alters onward transmission could also substantially reduce infections. Several gaps and research needs have been identified by researchers in the field and via this narrative literature review. For example, future modelling to inform gonorrhoea vaccine development and implementation should consider additional populations that are at high risk of N. gonorrhoeae infection, especially in low- and middle-income settings, as well as the impact of vaccination on the potential adverse sexual and reproductive health outcomes of infection. In addition, more detailed and robust epidemiological, biological, and behavioural data is needed to enable more accurate and robust modelling of gonorrhoea vaccine impact to inform future scientific and public health decision-making.

The role of vaccine status homophily in the COVID-19 pandemic: a cross-sectional survey with modelling

BackgroundVaccine homophily describes non-heterogeneous vaccine uptake within contact networks. This study was performed to determine observable patterns of vaccine homophily, as well as the impact of vaccine homophily on disease transmission within and between vaccination groups under conditions of high and low vaccine efficacy.MethodsResidents of British Columbia, Canada, aged ≥ 16 years, were recruited via online advertisements between February and March 2022, and provided information about vaccination status, perceived vaccination status of household and non-household contacts, compliance with COVID-19 prevention guidelines, and history of COVID-19. A deterministic mathematical model was used to assess transmission dynamics between vaccine status groups under conditions of high and low vaccine efficacy.ResultsVaccine homophily was observed among those with 0, 2, or 3 doses of the vaccine. Greater homophily was observed among those who had more doses of the vaccine (p < 0.0001). Those with fewer vaccine doses had larger contact networks (p < 0.0001), were more likely to report prior COVID-19 (p < 0.0001), and reported lower compliance with COVID-19 prevention guidelines (p < 0.0001). Mathematical modelling showed that vaccine homophily plays a considerable role in epidemic growth under conditions of high and low vaccine efficacy. Furthermore, vaccine homophily contributes to a high force of infection among unvaccinated individuals under conditions of high vaccine efficacy, as well as to an elevated force of infection from unvaccinated to suboptimally vaccinated individuals under conditions of low vaccine efficacy.InterpretationThe uneven uptake of COVID-19 vaccines and the nature of the contact network in the population play important roles in shaping COVID-19 transmission dynamics.

Safety and efficacy of malaria vaccine candidate R21/Matrix-M in African children: a multicentre, double-blind, randomised, phase 3 trial

Recently, we found that a new malaria vaccine, R21/Matrix-M, had over 75% efficacy against clinical malaria with seasonal administration in a phase 2b trial in Burkina Faso. Here, we report on safety and efficacy of the vaccine in a phase 3 trial enrolling over 4800 children across four countries followed for up to 18 months at seasonal sites and 12 months at standard sites. We did a double-blind, randomised, phase 3 trial of the R21/Matrix-M malaria vaccine across five sites in four African countries with differing malaria transmission intensities and seasonality. Children (aged 5-36 months) were enrolled and randomly assigned (2:1) to receive 5 μg R21 plus 50 μg Matrix-M or a control vaccine (licensed rabies vaccine [Abhayrab]). Participants, their families, investigators, laboratory teams, and the local study team were masked to treatment. Vaccines were administered as three doses, 4 weeks apart, with a booster administered 12 months after the third dose. Half of the children were recruited at two sites with seasonal malaria transmission and the remainder at standard sites with perennial malaria transmission using age-based immunisation. The primary objective was protective efficacy of R21/Matrix-M from 14 days after third vaccination to 12 months after completion of the primary series at seasonal and standard sites separately as co-primary endpoints. Vaccine efficacy against multiple malaria episodes and severe malaria, as well as safety and immunogenicity, were also assessed. This trial is registered on ClinicalTrials.gov, NCT04704830, and is ongoing. From April 26, 2021, to Jan 12, 2022, 5477 children consented to be screened, of whom 1705 were randomly assigned to control vaccine and 3434 to R21/Matrix-M; 4878 participants received the first dose of vaccine. 3103 participants in the R21/Matrix-M group and 1541 participants in the control group were included in the modified per-protocol analysis (2412 [51·9%] male and 2232 [48·1%] female). R21/Matrix-M vaccine was well tolerated, with injection site pain (301 [18·6%] of 1615 participants) and fever (754 [46·7%] of 1615 participants) as the most frequent adverse events. Number of adverse events of special interest and serious adverse events did not significantly differ between the vaccine groups. There were no treatment-related deaths. 12-month vaccine efficacy was 75% (95% CI 71-79; p<0·0001) at the seasonal sites and 68% (61-74; p<0·0001) at the standard sites for time to first clinical malaria episode. Similarly, vaccine efficacy against multiple clinical malaria episodes was 75% (71-78; p<0·0001) at the seasonal sites and 67% (59-73; p<0·0001) at standard sites. A modest reduction in vaccine efficacy was observed over the first 12 months of follow-up, of similar size at seasonal and standard sites. A rate reduction of 868 (95% CI 762-974) cases per 1000 children-years at seasonal sites and 296 (231-362) at standard sites occurred over 12 months. Vaccine-induced antibodies against the conserved central Asn-Ala-Asn-Pro (NANP) repeat sequence of circumsporozoite protein correlated with vaccine efficacy. Higher NANP-specific antibody titres were observed in the 5-17 month age group compared with 18-36 month age group, and the younger age group had the highest 12-month vaccine efficacy on time to first clinical malaria episode at seasonal (79% [95% CI 73-84]; p<0·001) and standard (75% [65-83]; p<0·001) sites. R21/Matrix-M was well tolerated and offered high efficacy against clinical malaria in African children. This low-cost, high-efficacy vaccine is already licensed by several African countries, and recently received a WHO policy recommendation and prequalification, offering large-scale supply to help reduce the great burden of malaria in sub-Saharan Africa. The Serum Institute of India, the Wellcome Trust, the UK National Institute for Health Research Oxford Biomedical Research Centre, and Open Philanthropy.

A Dynamic Model of Information‐Vaccination‐Disease That Accounts for Emerging Viral Variants: Model Development and a Case Study for COVID‐19 in Iceland

Pathogens mutate as diseases spread, and variants that become epidemic or pandemic strains have higher transmission rates and a greater capacity to escape vaccine protection. Considering different vaccine efficacy and vaccination rates is of great significance for the prevention and control of infectious diseases. The spread of vaccination information and the level of trust in vaccinations determine whether people will choose to be vaccinated. To analyze these factors, we developed mean‐field equations for system dynamics to model the complex system of vaccine information dissemination and vaccination, calculated the basic reproduction rate number, and used the Icelandic COVID‐19 outbreak (Omicron variant) as a case study. We found that in the face of emerging variants, increasing vaccine efficacy is more effective than increasing vaccination rates. If vaccine efficacy increases from 40% to 90%, infections can be decreased by 98.5%. However, even a 100% vaccination rate cannot stop the spread of a mutated virus if vaccine efficacy falls below a certain level. High vaccination rates decrease the virus transmission rate. If the efficacy of the vaccine diminishes, the infection will spread rapidly, leading to a greater number of individuals becoming infected with the infectious disease. Due to the high vaccine efficacy against major illnesses and fatalities, improving vaccination rates can lower deaths. Iceland could decrease deaths by 44.8% by raising the vaccination rate from 75.9% to 95.0%. To combat emerging virus variants, it is therefore necessary to both create more effective vaccines and raise awareness of the benefits of vaccination to increase vaccination rates.

Enhancing Protective Antibodies against Opioids through Antigen Display on Virus-like Particles.

Opioid use disorder (OUD) has become a public health crisis, with recent significant increases in the number of deaths due to overdose. Vaccination can provide an attractive complementary strategy to combat OUD. A key for high vaccine efficacy is the induction of high levels of antibodies specific to the drug of abuse. Herein, a powerful immunogenic carrier, virus-like particle mutant bacteriophage Qβ (mQβ), has been investigated as a carrier of a small molecule hapten 6-AmHap mimicking heroin. The mQβ-6-AmHap conjugate was able to induce significantly higher levels of IgG antibodies against 6-AmHap than mice immunized with the corresponding tetanus toxoid-6-AmHap conjugate in head-to-head comparison studies in multiple strains of mice. The IgG antibody responses were persistent with high anti-6-AmHap titers 600 days after being immunized with mQβ-6-AmHap. The antibodies induced exhibited strong binding toward multiple heroin/morphine derivatives that have the potential to be abused, while binding weakly to medications used for OUD treatment and pain relief. Furthermore, vaccination effectively reduced the impacts of morphine on mice in both ambulation and antinociception assays, highlighting the translational potential of the mQβ-6-AmHap conjugate to mitigate the harmful effects of drugs of abuse.

Durability of single-dose HPV vaccination in young Kenyan women: randomized controlled trial 3-year results

Cervical cancer burden is high where prophylactic vaccination and screening coverage are low. We demonstrated in a multicenter randomized, double-blind, controlled trial that single-dose human papillomavirus (HPV) vaccination had high vaccine efficacy (VE) against persistent infection at 18 months in Kenyan women. Here, we report findings of this trial through 3 years of follow-up. Overall, 2,275 healthy women aged 15–20 years were recruited and randomly assigned to receive bivalent (n = 760), nonavalent (n = 758) or control (n = 757) vaccine. The primary outcome was incident-persistent vaccine type-specific cervical HPV infection. The primary evaluation was superiority analysis in the modified intention-to-treat (mITT) HPV 16/18 and HPV 16/18/31/33/45/52/58 cohorts. The trial met its prespecified end points of vaccine type-specific persistent HPV infection. A total of 75 incident-persistent infections were detected in the HPV 16/18 mITT cohort: 2 in the bivalent group, 1 in the nonavalent group and 72 in the control group. Nonavalent VE was 98.8% (95% CI 91.3–99.8%, P < 0.0001) and bivalent VE was 97.5% (95% CI 90.0–99.4%, P < 0.0001). Overall, 89 persistent infections were detected in the HPV 16/18/31/33/45/52/58 mITT cohort: 5 in the nonavalent group and 84 in the control group; nonavalent VE was 95.5% (95% CI 89.0–98.2%, P < 0.0001). There were no vaccine-related severe adverse events. Three years after vaccination, single-dose HPV vaccination was highly efficacious, safe and conferred durable protection. ClinicalTrials.gov no. NCT03675256.

1632. Bivalent RSV Prefusion F-Based Subunit Vaccine Generates High Neutralizing Titers in Older Adults

Abstract Background Respiratory syncytial virus (RSV) is an important cause of lower respiratory tract illness (LRTI) in older adults. The search for an effective RSV vaccine was hindered by poor functional immunogenicity of early vaccine candidates that did not have F antigens stabilized in the prefusion state. RSVpreF, Pfizer’s bivalent stabilized prefusion F subunit vaccine candidate containing preF antigens against two major RSV subgroups (A and B), elicited robust neutralizing responses in phase 1/2 studies. Methods The RSV Vaccine Efficacy Study in Older Adults Immunized Against RSV Disease (RENOIR) is a phase 3, multicenter, randomized, double-blinded, placebo-controlled study evaluating vaccine efficacy (VE) to prevent LRTI in adults ≥60 years of age over two RSV seasons (NCT05035212). Participants were randomly assigned (1:1 ratio) to receive a single intramuscular injection of RSVpreF at a dose of 120μg or placebo. The study demonstrated a VE of 88.9% for LRTI-RSV with ≥3 symptoms at the end of the first RSV season. A secondary objective was to describe the immune responses induced by RSVpreF following vaccination. The immunogenicity subset included 1150 participants enrolled from sites in the United States and Japan. Results Here we report the immunogenicity results one month after RSVpreF vaccination. The neutralization titer geometric mean fold rises (GMFRs) ranged from 11.6 to 12.7 for RSV A and B, respectively, and GMFRs for combined RSV A/B neutralizing responses ranged from 12.0 to 13.0 for subgroups stratified by age (60-69, 70-79 and 80+ years). RSV A/B GMFRs in participants with prespecified chronic conditions were similar to or higher than those without, with 11.4, 13.0 and 14.8, respectively, for subgroups stratified based on none, at least one prespecified chronic medical condition or at least one chronic cardiopulmonary condition. RSV Neutralizing GMTs Before and 1 Month Postvaccination 1 and Subgroup Analysis Conclusion High RSV neutralizing titers were observed one month after RSVpreF vaccination in adults 60 years and older, consistent with prior phase 1/2 studies. The study further shows similarly robust responses across age subgroups and baseline chronic conditions. Although there is no established correlate of protection, these high antibody responses corresponded with high RSVpreF VE in the first RSV season. Disclosures Agnieszka Zareba, MD PhD, Pfizer: Employee|Pfizer: Stocks/Bonds|Pfizer: Stocks/Bonds Qin Jiang, PhD, Pfizer: Employee|Pfizer: Employee|Pfizer: Stocks/Bonds|Pfizer: Stocks/Bonds Daniel P. Eiras, MD, MPH, Pfizer, Inc.: Stocks/Bonds Michael Patton, B.Sc., Pfizer Inc.: Employee|Pfizer Inc.: Stocks/Bonds Kumar Ilangovan, MD, MSPH, MMCi, Pfizer, Inc.: Employee|Pfizer, Inc.: Stocks/Bonds Elliot N. DeHaan, MD, Pfizer: Employee|Pfizer: Stocks/Bonds Tarek Mikati, MD,MPH, Pfizer: Stocks/Bonds Elena Kalinina, PhD, Pfizer: Pfizer employee|Pfizer: Stocks/Bonds David Cooper, PhD, Pfizer, Inc.: Stocks/Bonds Kenneth Koury, PhD, Pfizer: Employee|Pfizer: Stocks/Bonds Annaliesa S. Anderson, PhD, Pfizer: Employee|Pfizer: Stocks/Bonds Kena A. Swanson, Ph.D., Pfizer: Employee|Pfizer: Stocks/Bonds William C. Gruber, MD, Pfizer, Inc.: Employee|Pfizer, Inc.: Stocks/Bonds Alejandra C. Gurtman, M.D., Pfizer: Employee|Pfizer: Stocks/Bonds Beate Schmoele-Thoma, MD, Pfizer: Stocks/Bonds

HPV Vaccine Usage Among the U.S. Military Academy Corps ofCadets (2018-2025).

Human papillomavirus (HPV) is a common sexually transmitted virus that infects over 13 million people every year. Over 80% of sexually active adults will acquire HPV at some point in their lives, which is concerning since certain high-risk strains of HPV can cause six types of cancer. Vaccination against HPV is safe and effective, but despite high vaccine efficacy, vaccination rates are low among both service members and civilians. We conducted a retrospective, cross-sectional study to identify the percentage of United States Military Academy (USMA) Cadets who had received at least one HPV vaccine and those who completed the vaccine series. Deidentified vaccination and demographic data were retrieved from the Defense Health Agency Military Health System Data Repository (MDR) for all Cadets who were enrolled at USMA between January 2018 and May 2022 (graduating classes of 2018-2025). To identify the population of Cadets for our study and confirm presence of "any" vaccine in the MDR, Tdap vaccination information was also retrieved. The study population was defined as any Cadet who was enrolled at USMA between January 2018 and May 2022 (graduating classes of 2018-2025) and had record of an HPV and/or Tdap vaccine in the MDR. We compared demographic information between the identified population and known demographics of the USMA population to confirm that the retrieved data were consistent with population demographics. Descriptive statistics were performed to identify demographic differences based on vaccinated and unvaccinated Cadets and to determine the percentage of Cadets who received at least one HPV vaccine. Vaccine series completion was defined as the receipt of three HPV vaccine doses among those who reported receiving at least one dose of HPV vaccine or two doses if vaccinated before the age 15. A total of 9,567 Cadets were assessed for eligibility with 9,433 having Tdap and/or HPV vaccine on record. Of these Cadets, 5,738/9,433 (60.8%) had received at least one HPV vaccine. Of those starting the series, 4,492 completed the two- or three-dose series for a completion rate of 47.6%. We found HPV vaccine completion rate among female Cadets (55.6%) is higher than that of male Cadets (45.2%). More Cadets from minority groups received one vaccine; however, full completion rates were similar for both the groups (48.1%). In contrast, the percentage of Cadets vaccinated against Tdap was 97.2%. Most of those vaccinated received their first vaccine between the ages of 11 and 15 (53.0%) and their final vaccine after they turned 16 (68.9%). Though the vaccination rate among the Corps of Cadets is comparable to the public, it is still less than the 80.0% goal set by the Healthy People 2030 objective. Based on these results, we recommend that the USMA modify its policy on HPV vaccine administration to encourage more vaccine uptake. We also conclude that further studies on the rationale for avoiding the vaccine are necessary to better inform educational campaigns and mitigate stigma.

Modeling vaccination strategies with limited early COVID-19 vaccine access in low- and middle-income countries: A case study of Thailand

Low- and middle-income countries faced significant challenges in accessing COVID-19 vaccines during the early stages of the pandemic. In this study, we utilized an age-structured modeling approach to examine the implications of various vaccination strategies, vaccine prioritization, and vaccine rollout speeds in Thailand, an upper-middle-income country experiencing vaccine shortages during the early stages of the pandemic. The model directly compares the effectiveness of several vaccination strategies, including the heterologous vaccination where CoronaVac (CV) vaccine was administered as the first dose, followed by ChAdOx1 nCoV-19 (AZ) vaccine as the second dose, under varying disease transmission dynamics. We found that the traditional AZ homologous vaccination was more effective than the CV homologous vaccination, regardless of disease transmission dynamics. However, combining CV and AZ vaccines via either parallel homologous or heterologous vaccinations was more effective than relying solely on AZ homologous vaccination. Additionally, prioritizing vaccination for the elderly aged 60 years and above was the most effective way to reduce mortality when community transmission is well-controlled. On the other hand, prioritizing workers aged 20–59 was most effective in lowering COVID-19 cases, irrespective of the transmission dynamics. Lastly, despite the vaccine prioritization strategy, rapid vaccine rollout speeds were crucial in reducing COVID-19 infections and deaths. These findings suggested that in low- and middle-income countries where early access to high-efficacy vaccines might be limited, obtaining any accessible vaccines as early as possible and using them in parallel with other higher-efficacy vaccines might be a better strategy than waiting for and relying solely on higher-efficacy vaccines.

Genotype analysis of rotaviruses isolated from children during a phase III clinical trial with the hexavalent rotavirus vaccine in China

The oral hexavalent live human-bovine reassortant rotavirus vaccine (RV6) developed by Wuhan Institute of Biological Products Co., Ltd (WIBP) has finished a randomized, placebo-controlled phase III clinical trial in four provinces of China in 2021. The trail demonstrated that RV6 has a high vaccine efficacy against the prevalent strains and is safe for use in infants. During the phase III clinical trial (2019–2021), 200 rotavirus-positive fecal samples from children with RV gastroenteritis (RVGE) were further studied. Using reverse transcription-polymerase chain reaction and high-throughput sequencing, VP7 and VP4 sequences were obtained and their genetic characteristics, as well as the differences in antigenic epitopes of VP7, were analyzed in detail. Seven rotavirus genotypes were identified. The predominant rotavirus genotype was G9P [8] (77.0%), followed by prevalent strains G8P [8] (8.0%), G3P [8] (3.5%), G3P [9] (1.5%), G1P [8] (1.0%), G2P [4] (1.0%), and G4P [6] (1.0%). The amino acid sequence identities of G1, G2, G3, G4, G8, and G9 genotypes of isolates compared to the vaccine strains were 98.8%, 98.2%–99.7%, 88.4%–99.4%, 98.2%, 94.2%–100%, and 93.9%–100%, respectively. Notably, the vaccine strains exhibited high similarity in amino acid sequence, with only minor differences in antigenic epitopes compared to the Chinese endemic strains. This supports the potential application of the vaccine in preventing diseases caused by rotaviruses.

The value of herpes zoster prevention in people aging with HIV: A narrative review.

Review the evidence on the incidence and impact of herpes zoster among people living with HIV and the potential impact of recombinant zoster vaccine for people aging with HIV. Narrative review. Although antiretroviral therapy has substantially reduced the risk of herpes zoster among people living with HIV, they remain at an increased risk compared with the general population. Among people aging with HIV, aging per se is now the main risk factor for herpes zoster. Beyond pain, herpes zoster is also associated with a risk of sight-threatening complications in case of trigeminal involvement, disseminated diseases and stroke. Post-herpetic neuralgia is also a potential threat to the quality of life of people aging with HIV. The recombinant zoster vaccine has demonstrated high and sustained efficacy in the prevention of herpes zoster, post-herpetic neuralgia, and other herpes zoster complications in the general population. Immunogenicity data among people living with HIV with high CD4+ T-cell count and controlled viral load are comparable to those among the general population. Real-life effectiveness data indicate high vaccine efficacy among immunocompromised patients other than people living with HIV. High vaccine price, vaccine hesitancy, and limited disease and vaccine awareness represent potential hurdles for high vaccine uptake among people aging with HIV in Europe. Herpes zoster, and its complications, is a vaccine-preventable disease of aging people. Given its impact on quality of life, herpes zoster prevention using recombinant zoster vaccine is a safe strategy to be considered in every person aging with HIV.

A Brighton Collaboration standardized template with key considerations for a benefit/risk assessment for the Novavax COVID-19 Vaccine (NVX-CoV2373), a recombinant spike protein vaccine with Matrix-M adjuvant to prevent disease caused by SARS-CoV-2 viruses

Novavax, a global vaccine company, began evaluating NVX-CoV2373 in human studies in May 2020 and the pivotal placebo-controlled phase 3 studies started in November 2020; five clinical studies provided adult and adolescent clinical data for over 31,000 participants who were administered NVX-CoV2373. This extensive data has demonstrated a well-tolerated response to NVX-CoV2373 and high vaccine efficacy against mild, moderate, or severe COVID-19 using a two-dose series (Dunkle et al., 2022) [1], (Heath et al., 2021) [2], (Keech et al., 2020) [3], (Mallory et al., 2022) [4]. The most common adverse events seen after administration with NVX-CoV2373 were injection site tenderness, injection site pain, fatigue, myalgia, headache, malaise, arthralgia, nausea, or vomiting. In addition, immunogenicity against variants of interest (VOI) and variants of concern (VOC) was established with high titers of ACE2 receptor-inhibiting and neutralizing antibodies in these studies (EMA, 2022) [5], (FDA, 2023) [6]. Further studies on correlates of protection determined that titers of anti-Spike IgG and neutralizing antibodies correlated with efficacy against symptomatic COVID-19 established in clinical trials (p < 0.001 for recombinant protein vaccine and p = 0.005 for mRNA vaccines for IgG levels) (Fong et al., 2022) [7]. Administration of a booster dose of the recombinant protein vaccine approximately 6 months following the primary two-dose series resulted in substantial increases in humoral antibodies against both the prototype strain and all evaluated variants, similar to or higher than the antibody levels observed in phase 3 studies that were associated with high vaccine efficacy (Dunkle et al., 2022) [1], (Mallory et al., 2022) [4]. These findings, together with the well tolerated safety profile, support use of the recombinant protein vaccine as primary series and booster regimens.