Safety, tolerability, and immunogenicity of an adult-specific pneumococcal conjugate vaccine, V116, in people living with HIV (STRIDE-7): a two-part, parallel-group, randomised, active comparator-controlled, international, phase 3 trial.

Abstract

BACKGROUND People living with HIV are at high risk of pneumococcal disease, and evidence of pneumococcal conjugate vaccine (PCV) safety and efficacy is needed. We aimed to evaluate the safety, tolerability, and immunogenicity of V116 (an adult-specific 21-valent PCV) in this population. METHODS This two-part phase 3 trial was conducted at 20 centres in Belgium, Chile, France, South Africa, Thailand, and the USA. Part A was a randomised, active comparator-controlled, parallel-group, multicentre, double-blind trial in adults aged 18 years or older living with HIV (CD4 counts ≥50 cells per μL, plasma HIV RNA load <50 000 copies per mL, and combination antiretroviral therapy for ≥6 weeks). In part A, participants were randomly assigned (1:1), using an interactive response technology system, to receive V116 followed by placebo 8 weeks later or 15-valent PCV (PCV15) followed by 23-valent pneumococcal polysaccharide vaccine (PPSV23) 8 weeks later. Part B was an open-label trial of PCV15 after receiving V116 in part A (once all participants completed follow-up). Unmasked study personnel administered a 0·5 mL intramuscular dose of each vaccine. The funder, site staff, data management team, and participants were masked. Blood samples were collected on day 1 and at 30 days and 12 weeks post-vaccination in part A and on days 1 and 30 in part B. The primary outcome in part A, assessed in the per-protocol population, was serotype-specific opsonophagocytic activity geometric mean titres 30 days post-vaccination for the 13 serotypes common to V116 and PCV15 plus PPSV23 and for the eight serotypes unique to V116. Part B was exploratory. Immunogenicity was assessed using descriptive statistics. This study is registered with ClinicalTrials.gov, NCT05393037, and EudraCT, 2021-006710-36 (completed). FINDINGS Adults were enrolled and followed up in part A between July 13, 2022, and July 13, 2023, and in part B between Oct 18, 2023, and Jan 25, 2024. 313 participants were randomly assigned (156 in the V116 plus placebo group and 157 in the PCV15 plus PPSV23 group) and 304 (97%) completed part A (152 in each group). 126 (81%) of 155 participants in the V116 plus placebo group as-treated population from part A received PCV15 in part B (administration interval median 11·4 months [range 9·5-16·9]). 221 (71%) participants were male and 91 (29%) were female. The mean age was 45 years (SD 13). V116 was immunogenic for all 21 serotypes contained in the vaccine, and immune responses on day 30 were generally similar to those seen with PCV15 plus PPSV23 at week 12 for the 13 common serotypes and higher for the eight serotypes unique to V116. In part A, fewer participants had at least one adverse event in the V116 plus placebo group (111 [72%] of 155 vs 141 [91%] of 155 in the PCV15 plus PPSV23 group) with a lower frequency of injection-site adverse events (79 [51%] vs 130 [84%]); serious adverse events were low (four [3%] vs six [4%]) and none were vaccine related. One non-vaccine-related death with an unknown cause occurred in part A in the V116 plus placebo group. INTERPRETATION V116 was well tolerated and immunogenic for all 21 serotypes, supporting the use of this vaccine in adults living with HIV. Adults at high risk of pneumococcal disease due to underlying comorbid conditions, such as HIV, might benefit from receiving V116. The serotypes in V116, including the eight unique serotypes, are expected to provide broader protection against pneumococcal disease than currently licensed vaccines. FUNDING MSD.