Kyla Hayford

The development of respiratory syncytial virus (RSV) vaccines has advanced substantially in recent years, with three prefusion F (preF) protein-based and mRNA platforms achieving regulatory approval for use in older adults. Among licensed protein subunit vaccines, key design differences include the use of adjuvants and antigen valency, raising important questions regarding the necessity and impact of adjuvantation for RSV prevention. This narrative review examines the role of adjuvants in RSV vaccine development, with a focus on immunogenicity, vaccine effectiveness, safety, and implications for older adults and immunocompromised (IC) populations. Adjuvants can sometimes enhance immune responses but may increase reactogenicity. Clinical trials and observational studies demonstrate that both adjuvanted (RSVPreF3/AS01E) and non-adjuvanted (bivalent RSVpreF) vaccines provide substantial and comparable protection against RSV-related lower respiratory tract disease and hospitalization with comparable safety. The totality of evidence to date does not suggest an effectiveness advantage for adjuvanted vaccines among IC populations. Overall, these findings suggest that effective protection against RSV disease in adults can be achieved with or without adjuvantation.

Few studies have reported vaccine effectiveness (VE) and population-level impact of the 13-valent pneumococcal conjugate vaccination (PCV13) among children with immunocompromising or chronic medical conditions putting them at risk of developing pneumococcal disease. The objective of this systematic literature review (SLR) was to summarize the efficacy, effectiveness, and impact of PCV13 in the prevention of invasive pneumococcal disease (IPD) and all-cause pneumonia among children with risk conditions. Peer-reviewed studies published between January 2000 and July 2024 were identified in MEDLINE, Embase, CENTRAL, and CDSR. Of 3008 records identified, full texts of 189 studies (6.3%) were reviewed and 11 (0.4%) studies evaluating PCV13 alone or in combination with PCV7 were included. Vaccine effectiveness or impact of PCV13 was reported in children with sickle cell disease (SCD; n = 2), HIV (n = 4), post-transplant conditions (n = 1), cancer (n = 1), combined immunocompromising conditions (n = 1), combined chronic medical and immunocompromising conditions (n = 1), and congenital heart disease (n = 1). In children with immunocompromising conditions, VE against PCV13-type IPD ranged between 83.8% and 91%. Compared to the pre-PCV era, the introduction of PCV13 in pediatric immunization programs was associated with a relative reduction of IPD due to any serotype between 86% and 100% in children SCD and 55% to 80% in children with cancer. PCV impact, as measured by incidence rate reductions, among children with HIV varied by comparison period, age group and outcome and ranged from 9.1% to 81% for any IPD. These findings support PCV vaccination for children with risk conditions although evidence was limited and heterogeneous.

Purpose To estimate pneumococcal conjugate vaccine (PCV) national program impact on pneumococcal complicated pneumonia (PnCP) based on changes in PnCP population-based incidence, PnCP proportion of all-cause complicated pneumonia (or invasive pneumococcal disease), and PnCP serotype distribution. Methods MEDLINE, EMBASE, and Global Index Medicus articles (2001-March 2022) reporting laboratory-confirmed PnCP studies were stratified by age group, outcome measure, PCV program period(s) (pre-PCV, transition, and post-PCV), serotype distribution (based on serotyping methodology used), and PCV serotype formulation. Random effect meta-analysis of the total number of serotyped isolates within each study was used to calculate pooled serotype-specific percentages. Results Of 1360 publications screened, the 134 studies included from 30 countries differed widely by methodological approaches. Pediatric PnCP incidence tended to decline from pre-PCV to post-PCV periods, as did PnCP as a proportion of all-cause complicated pneumonia from transition to post-PCV periods. Studies describing changes in serotype distribution by PCV program period applied detection methods that varied from pre-PCV period microbiological culture with Quellung serotyping to in the transition and post-PCV periods molecular methods like PCR. Meta-analysis revealed near elimination of pediatric PCV7-serotype PnCP between pre- and post-PCV, while the PCV13nonPCV7 percentage increased from 51.1% pre-PCV period to 76.5% in the transition period, remaining stable post-PCV period. Non-PCV13 serotypes increased slightly from low baseline numbers. Adult data were lacking or inconsistent. Conclusions Although studies were heterogeneous, pediatric PnCP incidence and proportion tended to decline from pre-PCV to post-PCV periods, and PCV13nonPCV7 serotype distribution percentage remained unchanged from transition to post-PCV period. Standardization of PnCP surveillance methods, definitions, and reporting is needed to evaluate accurately PCV program impact.

Residual blood specimens collected at health facilities may be a source of samples for serosurveys of adults, a population often neglected in community-based serosurveys. Anonymized residual blood specimens were collected from individuals 15 – 49 years of age attending two sub-district hospitals in Palghar District, Maharashtra, from November 2018 to March 2019. Specimens also were collected from women 15 – 49 years of age enrolled in a cross-sectional, community-based serosurvey representative at the district level that was conducted 2 – 7 months after the residual specimen collection. Specimens were tested for IgG antibodies to measles and rubella viruses. Measles and rubella seroprevalence estimates using facility-based specimens were 99% and 92%, respectively, with men having significantly lower rubella seropositivity than women. Age-specific measles and rubella seroprevalence estimates were similar between the two specimen sources. Although measles seropositivity was slightly higher among adults attending the facilities, both facility and community measles seroprevalence estimates were 95% or higher. The similarity in measles and rubella seroprevalence estimates between the community-based and facility serosurveys highlights the potential value of residual specimens to approximate community seroprevalence.

Residual blood specimens provide a sample repository that could be analyzed to estimate and track changes in seroprevalence with fewer resources than household-based surveys. We conducted parallel facility and community-based cross-sectional serological surveys in two districts in India, Kanpur Nagar District, Uttar Pradesh, and Palghar District, Maharashtra, before and after a measles-rubella supplemental immunization activity (MR-SIA) from 2018 to 2019. Anonymized residual specimens from children 9 months to younger than 15 years of age were collected from public and private diagnostic laboratories and public hospitals and tested for IgG antibodies to measles and rubella viruses. Significant increases in seroprevalence were observed following the MR SIA using the facility-based specimens. Younger children whose specimens were tested at a public facility in Kanpur Nagar District had significantly lower rubella seroprevalence prior to the SIA compared to those attending a private hospital, but this difference was not observed following the SIA. Similar increases in rubella seroprevalence were observed in facility-based and community-based serosurveys following the MR SIA, but trends in measles seroprevalence were inconsistent between the two specimen sources. Despite challenges with representativeness and limited metadata, residual specimens can be useful in estimating seroprevalence and assessing trends through facility-based sentinel surveillance.

Background: In alignment with the Measles and Rubella (MR) Strategic Elimination plan, India conducted a mass measles and rubella vaccination campaign across the country between 2017 and 2020 to provide a dose of MR containing vaccine to all children aged 9 months to 15 years. We estimated campaign vaccination coverage in five districts in India and assessed campaign awareness and factors associated with vaccination during the campaign to better understand reasons for not receiving the dose. Methods and findings: Community-based cross-sectional serosurveys were conducted in five districts of India among children aged 9 months to 15 years after the vaccination campaign. Campaign coverage was estimated based on home-based immunization record or caregiver recall. Campaign coverage was stratified by child- and household-level risk factors and descriptive analyses were performed to assess reasons for not receiving the campaign dose. Three thousand three hundred and fifty-seven children aged 9 months to 15 years at the time of the campaign were enrolled. Campaign coverage among children aged 9 months to 5 years documented or by recall ranged from 74.2% in Kanpur Nagar District to 90.4% in Dibrugarh District, Assam. Similar coverage was observed for older children. Caregiver awareness of the campaign varied from 88.3% in Hoshiarpur District, Punjab to 97.6% in Dibrugarh District, Assam, although 8% of children whose caregivers were aware of the campaign were not vaccinated during the campaign. Failure to receive the campaign dose was associated with urban settings, low maternal education, and lack of school attendance although the associations varied by district. Conclusion: Awareness of the MR vaccination campaign was high; however, campaign coverage varied by district and did not reach the elimination target of 95% coverage in any of the districts studied. Areas with lower coverage among younger children must be prioritized by strengthening the routine immunization programme and implementing strategies to identify and reach under-vaccinated children.

Higher valency pneumococcal conjugate vaccines (PCV15 and PCV20) have been developed to address the disease burden of current non-vaccine serotypes. This review describes the epidemiological characteristics of serotypes beyond PCV13 (serotypes 8, 10A, 11A, 12F, 15B/C, 22F, and 33F; PCV20nonPCV13 serotypes). Peer-reviewed studies published between 1 January 2010 (the year PCV13 became available) and 18 August 2020 were systematically reviewed (PROSPERO number: CRD42021212875). Data describing serotype-specific outcomes on disease proportions, incidence, severity, and antimicrobial non-susceptibility were summarized for individual and aggregate PCV20nonPCV13 serotypes by age group and by type and duration of pediatric PCV immunization program. Of 1168 studies, 127 (11%) were included in the analysis. PCV20nonPCV13 serotypes accounted for 28% of invasive pneumococcal disease (IPD), although the most frequent serotypes differed between children (10A, 15B/C) and adults (8, 12F, 22F). In children, serotype 15B/C tended to be more frequently associated with pneumococcal meningitis and acute otitis media; in adults, serotype 8 was more frequently associated with pneumonia and serotype 12F with meningitis. Serotypes 10A and 15B/C in children and 11A and 15B/C in adults were often associated with severe IPD. Serotype 15B/C was also among the most frequently identified penicillin/macrolide non-susceptible PCV20nonPCV13 serotypes. These results could inform decision making about higher valency PCV choice and use.