Determining the Value of Correlates of Protection to Ascertain Pneumococcal Vaccine Efficacy in Adults Living with HIV: A Scoping Review

Abstract

Background People Living With HIV(PLWH) remain susceptible to severe diseases caused by Streptococcus pneumoniae. In this scoping review, we synthesised existing evidence to determine the value of Correlates of Protection (CoP) to ascertain pneumococcal vaccines efficacy in adult PLWH and identify knowledge gaps. Methods Using the Joanna Biggs Institute framework (2022), our search strategy included 17 keywords across five databases. We retrieved 3123 studies gathered in the Covidence software. Two reviewers independently excluded 1549 duplicates. Of the 1574 remaining, 1274 articles were ineligible. Of the 300 studies with full-text reviews, 56 were included for data extraction. Findings 9.3% of selected studies were from high-income countries, and 59.3% of included adult participants were males aged 18-84 years. Of the studies, 57.2% were high-quality randomised controlled trials (RCTs), supporting vaccination in adult PLWH with PCV followed by PPSV23 after 8 weeks, finding this regimen safe and cost-effective. Pneumococcal carriage in adult PLWH was 7.3% and mucosal IgA showed a 48-fold rise with vaccination, even in people with low CD4+ cell counts of <200 cells/mm3. Serum pneumococcal IgG antibody titers against S. pneumoniae – which predict protection - were assessed by ELISA in 30 studies. PCVs perform better with a 2-7-fold increase in geometric mean concentration (GMC) after vaccination compared to a <2-4-fold increase for PPSV23 in adult PLWH. In 12 studies, a 2-4-fold rise in Opsonophagocytic killing Assay (OPA) GMT was reported versus a >4-fold increase in HIV negative people. MOPA, another way to identify CoP, showed adequate protection with an opsonic index of 5.6 after sequential PCV and then PPSV23 vaccination. Optimal immune responses for, PCV then PPSV23 occurred in people whose CD4 + count was > 200 cells/mm³) and HIV viral load was <1000 copies/ml. The number of memory B cells is associated with a higher antibody response following PCV13 vaccination, whereas PPSV23 vaccination is linked to a lower or impaired memory B cell response. No significant changes in memory B cells were observed after PCV7 vaccination. Both pneumococcal conjugate vaccines (PCVs) and PPSV23 are generally well iii tolerated up to 60 days post-vaccination. However, antibody levels tend to wane by one year in adult PLWH, even among those with CD4+ counts above 200 cells/mm³, partially attributed to HIV-related B cell dysfunction, which includes shifts toward exhausted and atypical memory B cell subsets that impair long-term immune memory and vaccine responsiveness. There is limited data on vaccine responses in PLWH with additional comorbidities or other immunosuppressive conditions. Conclusion Concerns remain over the durability of the pneumococcal vaccines in PLWH and the best CoP in this population. OPA titres appear to better correlate with protection in PLWH, and being on ART at the time of vaccination improves immune response. There is a paucity of data on CoP among susceptible adult PLWH with other comorbidities. Limited clinical trials exist of pneumococcal vaccines and using correlates of protection as the outcome in PLWH in LMICs. While PCVs offer better long-lasting immunity, in PLWH, lower antibody concentrations and waning antibody titres remain concerning. More longitudinal studies are needed in adult PLWH in LMIC to assess whether a higher protective threshold is needed and possible additional doses or booster vaccinations.