Expert Review of Vaccines最新文献

Introduction: Vaccination against SARS-CoV-2 is an integral pillar of the public health approach to COVID-19. With the emergence of variants of concern that increase transmissibility and escape from vaccine- or infection-induced protection, vaccines have been developed to more closely match the newly circulating SARS-CoV-2 strains to improve protection. The safety and immunogenicity of multiple authorized messenger RNA (mRNA)-based COVID-19 vaccines targeting the omicron sublineage (BA.1, BA.4/BA.5, and XBB.1.5) have been demonstrated in several clinical trials among adults and children.

Areas covered: This review will comprehensively detail the available evidence (published through July 2024) from ongoing clinical trials on omicron variant-containing mRNA-1273 vaccines administered as additional doses in previously vaccinated target demographics.

Expert opinion: Across three clinical trials, omicron variant-containing mRNA-1273 vaccines induced immune responses to vaccine-matched omicron strains as well as ancestral SARS-CoV-2, with a safety and reactogenicity profile comparable to the original mRNA-1273 vaccine. Combined with pivotal data demonstrating the safety, efficacy, and effectiveness of the original mRNA-1273 vaccine, these findings support the use of variant-containing mRNA-1273 vaccines and provide confidence that expeditious development of updated vaccines using this established mRNA platform can maintain protection against COVID-19.

Introduction: Global outbreaks involving mpox clade IIb began in mid-2022. Today, clade IIb and clade I outbreaks continue. Reliable mpox vaccines can prevent serious mpox disease and death.

Areas covered: Globally, two vaccines hold mpox indications, regardless of mpox viral clade: MVA-BN (Bavarian Nordic) and LC16m8 (KM Biologics). This review summarizes the human and pivotal animal data establishing safety and efficacy for MVA-BN and LC16m8, including real-world evidence gathered during mpox outbreaks from 2022 through 2024.

Expert opinion: Some regulatory decisions for MVA-BN and LC16m8 followed pathways based on surrogate outcomes, including lethal-challenge studies in nonhuman primates, among other atypical aspects. Nonetheless, MVA-BN and LC16m8 hold unencumbered registration in multiple countries. Effectiveness of MVA-BN as primary preventive vaccination (PPV) in humans against clade IIb mpox is clear from real-world studies; effectiveness of LC16m8 against clade IIb is likely from surrogate endpoints. Effectiveness of MVA-BN and LC16m8 as PPV against more-lethal clade I is likely, based on animal-challenge studies with multiple orthopoxvirus species and other studies. Both vaccines have solid safety records. MVA-BN's replication incompetence favors adoption, whereas LC16m8 has more pediatric data. Additional real-world evidence, in additional geographic settings and special populations (e.g. pregnancy, immune suppression, atopic dermatitis), is needed.

Introduction: There was no 13-valent pneumococcal conjugate vaccine (PCV13) adult antibody concentration threshold regulatory criterion for licensure - unlike the pediatric indication; consequently, for the adult indication, PCV13 serotype-specific opsonophagocytic activity (OPA) geometric mean titer (GMT) values were immunobridged to the 23-valent plain polysaccharide vaccine (PPV23) to infer efficacy against invasive pneumococcal disease (IPD). Subsequently, a double-blind, randomized, controlled PCV13 efficacy trial (CAPiTA) was performed in community-living, older adults to confirm efficacy against vaccine-serotype IPD (VT-IPD) and establish efficacy against vaccine-serotype pneumococcal community-acquired pneumonia (VT-CAP).

Areas covered: This article summarizes 31 publications from the PCV13 adult indication clinical development trials and other PCV13 clinical studies, organized by formulation, reactogenicity and safety, immunogenicity, coadministration, and clinical efficacy.

Expert opinion: PCV13 had a favorable safety profile with an OPA response generally greater than PPV23 irrespective of age and of previous pneumococcal vaccination. PCV13 primed for enhanced immune responses with subsequent PCV13 or PPV23 dosing. Conversely, PPV23 was shown to blunt the response to subsequent PCV13. CAPiTA demonstrated PCV13 efficacy for at least five years against both VT-IPD and VT-CAP. The PCV13 clinical development program provided fundamental insights into this vaccine's adult-specific immune responses and confirmed the advantages of conjugate over plain polysaccharide technology.

Introduction: Infant immunization programs using pneumococcal conjugate vaccines (PCVs) have reduced the rates of pneumococcal disease through direct vaccine-induced protection in vaccinated children and through indirect protection in non-vaccinated children and adults.

Areas covered: This review summarizes current evidence on the indirect protection of adults conferred by pediatric pneumococcal vaccination, including the impact on invasive pneumococcal disease (IPD) incidence and mortality, pneumonia admissions, and nasopharyngeal carriage prevalence. Factors affecting indirect protection against IPD are also discussed.

Expert opinion: Pediatric immunization with PCVs has substantially decreased vaccine-serotype IPD and pneumonia through indirect protection in both older (≥65 years of age) and younger adults, including those with underlying medical conditions. However, serotype replacement by non-vaccine serotypes, the persistence of some vaccine serotypes, and divergence of serotypes between children and adults have limited the impact of pediatric PCV programs on adult populations. Designing complementary vaccines that leverage indirect protection from pediatric immunization and target the most prevalent adult serotypes may be a preferred strategy to maximize the public health impact of pneumococcal vaccination.

Introduction: The mRNA vaccine technologies have progressed rapidly in recent years. The COVID-19 pandemic has accelerated the application of mRNA vaccines, with research and development and clinical trials underway for many vaccines. Application of the quality by design (QbD) framework to mRNA vaccine development and establishing standardized quality control protocols for mRNA vaccines are essential for the continued development of high-quality mRNA vaccines.

Areas covered: mRNA vaccines include linear mRNA, self-amplifying mRNA, and circular RNA vaccines. This article summarizes the progress of research on quality control of these three types of vaccines and presents associated challenges and considerations.

Expert opinion: Although there has been rapid progress in research on linear mRNA vaccines, their degradation patterns remain unclear. In addition, standardized assays for key impurities, such as residual dsRNA and T7 RNA polymerase, are still lacking. For self-amplifying mRNA vaccines, a key focus should be control of stability in vivo and in vitro. For circular RNA vaccines, standardized assays, and reference standards for determining degree of circularization should be established and optimized.

Introduction: The historical focus of vaccines on child health coupled with the advent of novel vaccines targeting adult populations necessitates exploring strategies for adult vaccine implementation.

Areas covered: This scoping review extracts insights from the past decade's experiences introducing adult vaccines in low- and middle-income countries. Among 25 papers reviewed, 19 focused on oral cholera vaccine, 2 on Meningococcal A vaccines, 2 on tetanus toxoid vaccine, 1 on typhoid vaccine, and 1 on Ebola vaccine. Aligned with WHO's Global Framework for New TB Vaccines for Adults and Adolescents, our findings center on vaccine availability, accessibility, and acceptance.

Expert opinion: Availability findings underscore the importance of understanding disease burden for prioritization, multi-sectoral collaboration during planning, and strategic resource allocation and coordination. Accessibility results highlight the benefits of leveraging existing health infrastructure and adequately training healthcare workers, and contextually tailoring vaccine delivery approaches to reach challenging sub-groups like working male adults. Central to fostering acceptance, resonant sensitization, and communication campaigns engaging the communities and utilizing trusted local leaders countered rumors and increased awareness and uptake. As we approach the introduction of a new adult TB vaccine, insights from this review equips decision-makers with key evidence-based recommendations to support successful and equitable vaccinations targeting adults.

Background: Respiratory syncytial virus (RSV), a common respiratory pathogen, can lead to severe symptoms, especially in older adults (OA). A recently developed RSV prefusion F protein (RSVPreF3 OA) vaccine confers high protection against RSV lower respiratory tract disease (LRTD) over two full RSV seasons. The aim of this study was to assess the potential public health impact of RSVPreF3 OA vaccination in the Japanese OA population.

Research design and methods: A static Markov model was used to estimate the number of symptomatic RSV cases, hospitalizations and deaths in the Japanese population aged ≥ 60 years over a 3-year time horizon. Japan-specific RSV epidemiology and healthcare resource use parameters were used; vaccine efficacy was derived from a phase 3 randomized study (AReSVi-006, NCT04886596). Vaccination coverage was set to 50%.

Results: Without vaccination, >5 million RSV acute respiratory illness (ARI) would occur (2.5 million LRTD and 2.8 million upper respiratory tract infections) leading to ~ 3.5 million outpatient visits, >534,000 hospitalizations and ~ 25,500 RSV-related deaths over 3 years. Vaccination could prevent > 1 million RSV-ARI cases, 728,000 outpatient visits, 143,000 hospitalizations and 6,840 RSV-related deaths.

Conclusions: RSVPreF3 OA vaccination is projected to have a substantial public health impact by reducing RSV-related morbidity and mortality in the OA population.

Background: Vaccination remains the cornerstone of defense against COVID-19 globally. This study aims to assess the safety and immunogenicity profile of innovative vaccines LYB001.

Research design and methods: This was a randomized, double-blind, parallel-controlled trial, in 100 healthy Chinese adults (21 to 72 years old). Three doses of 30 or 60 µg of SARS-CoV-2 RBD-based VLP vaccine (LYB001), or the SARS-CoV-2 RBD-based protein subunit vaccine (ZF2001, control group) were administered with a 28-day interval. Differences in the incidence of adverse events (AEs) and indicators of humoral and cellular immunity among the different groups were measured.

Results: No severe adverse events were confirmed to be vaccine-related, and there was no significant difference in the rate of adverse events between the LYB001 and control group or the age subgroups (p > 0.05). The LYB001 groups had significantly higher or comparable levels of seroconversion rates, neutralization antibody, S protein-binding antibody, and cellular immunity after whole vaccination than the control group.

Conclusions: Our findings support that LYB001 developed on the VLP platform is safe and well tolerated with favorable immunogenicity for fundamental vaccination in healthy adults. Therefore, further larger-scale clinical studies are warranted.

Trial registration: This trial was registered with ClinicalTrials.gov (NCT05552573).

Background: COVID-19 vaccines adapted to newly emerging circulating variants are necessary to better protect the population due to the evolving nature of the SARS-CoV-2 virus.

Research design and methods: The South African population was stratified by age and risk (defined by comorbidities such as diabetes, obesity, smoking, cancer, and asthma), and HIV status. The outcomes of different vaccination strategies based on age, risk, and HIV status were estimated using a Markov-decision tree model based on age-specific inputs derived from the literature and South African surveillance data.

Results: Vaccinating older adults and those with comorbidities was estimated to avert 111,179 infections 18,281 hospitalizations, and 3,868 deaths, resulting in savings of ZAR 1,260 million (USD 67 million) and ZAR 3,205 million (USD 170 million) in direct and indirect costs, respectively. Similar results were obtained when considering strategies targeting older adults and the HIV population. Expanding vaccination to 75% of the standard-risk population prevented more infections (401%), hospitalizations (167%), and deaths (67%) and increased the direct (232%) and indirect (455%) cost savings compared to the base case.

Conclusions: Implementing widespread vaccination strategies that utilize a vaccine adapted to the prevailing circulating variant in South Africa would result in significant public health and economic gains.

Background: Heterologous prime-boost schedules have been employed in SARS-CoV-2 vaccination, yet additional data on immunogenicity and effectiveness are still needed.

Research design and methods: Here, we measured the immunogenicity and effectiveness in the real-world setting of the mRNA booster dose in 181 subjects who had completed primary vaccination with ChAdOx1, BNT162b2, or mRNA1273 vaccines (IMMUNO_COV study; protocol code 18,869). The spike-specific antibody and B cell responses were analyzed up to 6 months after boosting.

Results: After an initial slower antibody response, the heterologous ChAdOx1/mRNA prime-boost formulation elicited spike-specific IgG titers comparable to homologous approaches, while spike-specific B cells showed a higher percentage of CD21^-CD27^- atypical cells compared to homologous mRNA vaccination. Mixed combinations of BNT162b2 and mRNA-1273 elicited an immune response comparable with homologous strategies. Non-significant differences in the Relative Risk of infection, calculated over a period of 18 months after boosting, were reported among homologous or heterologous vaccination groups, indicating a comparable relative vaccine effectiveness.

Conclusions: Our data endorse the heterologous booster vaccination with mRNA as a valuable alternative to homologous schedules. This approach can serve as a solution in instances of formulation shortages and contribute to enhancing vaccine strategies for potential epidemics or pandemics.