13. The Efficacy and Effectiveness of Pneumococcal Vaccines against Pneumococcal Pneumonia among Adults: A Systematic Review and Meta-Analysis

Abstract Background Two pneumococcal vaccines are currently recommended for use in U.S. adults: 23-valent pneumococcal polysaccharide vaccine (PPSV23) and 13-valent pneumococcal conjugate vaccine (PCV13). Recommendations for adult PCV13 use were supported by a large randomized-controlled trial (RCT) demonstrating PCV13 efficacy against pneumococcal pneumonia (PnPn) and vaccine-type (VT) PnPn in older adults. New pneumococcal conjugate vaccines are expected to be licensed for adults in late 2021 and recommendations for use among adults will be reviewed and revised, as needed. We conducted a systematic review to summarize evidence on the vaccine efficacy and effectiveness (VE) of PPSV23 and PCV13 against PnPn among adults. Methods We conducted a search of literature published from 1998 to February 2021 on PCV13 and PPSV23 VE studies using eight reference databases. Studies targeting adults with immunocompromising conditions were excluded. VE results with 95% confidence intervals (CI) were abstracted and stratified by vaccine product, outcome evaluated (PnPn and VT PnPn), study design, and effect measure. When applicable, random effects models were used to estimate pooled VE and I-squared statistic was reported to assess heterogeneity. Results Of 3,422 screened studies, we included 15 studies: three on PCV13 and 12 on PPSV23 (Table 1). In addition to the RCT, we identified two observational studies for PCV13 (Table 1); however, pooled VE of the observational studies was not estimated due to differences in methods for reporting results. Pooled PPSV23 VE against PnPn from two RCTs was 63% (95% CI: 31, 80 I2=0%). Pooled VE of PPSV23 against VT PnPn from three observational studies was 18% (95% CI: -35, 35 I2=38%). PPSV23 effectiveness against PnPn was limited with a pooled VE of 25% (95% CI: 7, 39 I2=78%) from nine observational studies. Conclusion Findings from observational studies supported PCV13 VE against VT PnPn reported in the RCT. Differences in the study design made the magnitude of PPSV23 effectiveness against PnPn and VT PnPn difficult to assess; however, findings from recent observational studies suggest PPSV23 provides limited protection against VT PnPn. Disclosures All Authors: No reported disclosures


Conclusion.
A very high rate of PLWH received vaccine, far exceeding local and national benchmarks, with EMR data unlikely to have fully captured all vaccines. The role of the COVID-19 pandemic in vaccine amongst PLWH is not yet known. While older age was associated with vaccine in adjusted analysis, the number of unvaccinated patients was small, confidence intervals wide, and associations consequently weak. Larger studies are needed to further investigate factors associated with vaccine receipt amongst PLWH.

Session: P-02. Adult Vaccines
Background. During the COVID-19 pandemic, adult vaccination in the United States (US) decreased substantially in 2020. Unlike other vaccine-preventable diseases where individuals may have experienced reduced risk due to COVID-related mitigation efforts (e.g., lockdown restrictions, use of face masks), individuals remained at risk of herpes zoster (HZ). This study projects the impact of reduced recombinant zoster vaccine (RZV) use on HZ cases and complications in the US.

Methods.
A multi-cohort Markov model estimated the impact of missed RZV vaccinations, by comparing scenarios with and without missed vaccinations between Apr-Dec 2020, on cases of HZ, postherpetic neuralgia (PHN), and quality-adjusted life-years (QALYs) among US adults aged ≥ 50 years. Epidemiology, RZV efficacy, and utility inputs were obtained from standard US sources, clinical trial data, and published literature. Missed doses were estimated using data on RZV doses and an assumed 43% reduction in RZV vaccinations during the pandemic, based on publicly available data. Deterministic sensitivity and scenario analyses were conducted.
Results. In 2020, approximately 21 million (M) RZV distributed doses were expected, including an estimated 9.2M RZV series initiations in Apr-Dec. An estimated 3.9M RZV series initiations were missed, resulting in 31,945 projected HZ cases, 2,714 PHN cases, and 610 lost QALYs projected over a 1-year follow up. If individuals with missed RZV initiations remain unvaccinated in 2021, avoidable HZ cases will increase to 63,117 over 2 years. Further, if the same number of RZV initiations are missed in 2021, 95,062 avoidable HZ cases are expected. In a sensitivity analysis assuming 30% RZV reduction, 18,020 avoidable HZ cases and 1,531 PHN cases were observed over 1 year.
Conclusion. Adding to the substantial COVID-19 infection-related morbidity and mortality, reduced RZV use during the pandemic resulted in further burden from avoidable HZ cases. Health care providers should continue to emphasize the importance of vaccination against HZ and other preventable diseases during the pandemic. Background. Two pneumococcal vaccines are currently recommended for use in U.S. adults: 23-valent pneumococcal polysaccharide vaccine (PPSV23) and 13-valent pneumococcal conjugate vaccine (PCV13). Recommendations for adult PCV13 use were supported by a large randomized-controlled trial (RCT) demonstrating PCV13 efficacy against pneumococcal pneumonia (PnPn) and vaccine-type (VT) PnPn in older adults. New pneumococcal conjugate vaccines are expected to be licensed for adults in late 2021 and recommendations for use among adults will be reviewed and revised, as needed. We conducted a systematic review to summarize evidence on the vaccine efficacy and effectiveness (VE) of PPSV23 and PCV13 against PnPn among adults.
Methods. We conducted a search of literature published from 1998 to February 2021 on PCV13 and PPSV23 VE studies using eight reference databases. Studies targeting adults with immunocompromising conditions were excluded. VE results with 95% confidence intervals (CI) were abstracted and stratified by vaccine product, outcome evaluated (PnPn and VT PnPn), study design, and effect measure. When applicable, random effects models were used to estimate pooled VE and I-squared statistic was reported to assess heterogeneity.

Conclusion.
Findings from observational studies supported PCV13 VE against VT PnPn reported in the RCT. Differences in the study design made the magnitude of PPSV23 effectiveness against PnPn and VT PnPn difficult to assess; however, findings from recent observational studies suggest PPSV23 provides limited protection against VT PnPn.
Disclosures. Background. MenACWY-TT (Nimenrix®), a quadrivalent meningococcal tetanus toxoid conjugate vaccine, was first licensed in 2012 and is available in 82 countries but not in the United States. MenACWY-TT is administered in infants as a 2 + 1 (6 weeks to < 6 months of age) or 1 + 1 (6 to < 12 months of age) schedule with the booster dose at 12 months of age, and from 12 months of age as a single dose. In addition to its widespread use to protect against meningococcal serogroups A, C, W, and Y, MenACWY-TT is a constituent of an investigational pentavalent meningococcal (MenABCWY) vaccine currently undergoing clinical development.
Methods. Using the MenACWY-TT Periodic Safety Update Report (PSUR) with format and content in accordance with Good Pharmacovigilance Practice Module VII and International Council for Harmonisation Guideline E2C, for data up to April 19, 2020, postmarketing safety experience with MenACWY-TT is considered. The PSUR data included herein are spontaneous adverse events (AEs) from the Pfizer safety database. AEs were coded by system organ class (SOC) and preferred term (PT) using MedDRA v.22.1J.

Conclusion.
Based on cumulative safety data in conjunction with existing efficacy and effectiveness data, the benefit-risk profile of MenACWY-TT remains favorable and is consistent with the safety profile of MenACWY-TT established in clinical studies.