A 21‑Valent Adult Pneumococcal Conjugate Vaccine (V116) Is Immunogenic and Well Tolerated in People Living with HIV: Results from STRIDE‑7

Highlights

– V116, a 21‑valent adult‑specific pneumococcal conjugate vaccine, elicited measurable opsonophagocytic activity (OPA) responses against all 21 vaccine serotypes in adults living with HIV.

– For the 13 serotypes shared with PCV15 and PPSV23, V116 responses at day 30 were generally similar to responses after PCV15 followed by PPSV23 at week 12; for the eight serotypes unique to V116, responses were higher than the comparator regimen.

– V116 had a favorable tolerability profile: fewer participants reported adverse events overall and at the injection site than those receiving PCV15 followed by PPSV23; serious adverse events were uncommon and none were considered vaccine‑related.

Background and clinical need

People living with HIV (PLWH) remain at increased risk of invasive pneumococcal disease (IPD) and pneumococcal pneumonia compared with the general population, even in settings with widespread antiretroviral therapy (ART). Risk is highest in those with lower CD4 counts and detectable viraemia, and outcomes can be severe. Pneumococcal conjugate vaccines (PCVs) reduce disease caused by vaccine serotypes through T cell–dependent immune responses and immunological memory; however, serotype coverage and durability of protection are important considerations when selecting vaccines for high‑risk adult populations.

Licensed adult pneumococcal vaccines include several formulations (eg, 13‑valent PCV, 15‑valent PCV, 20‑valent PCV, and 23‑valent polysaccharide vaccine [PPSV23]). V116 is a newly developed 21‑valent, adult‑specific PCV designed to broaden serotype coverage by including serotypes associated with residual disease in adults and serotypes less common in pediatric vaccines. Immunogenicity and safety data for PLWH are particularly important because HIV can blunt vaccine responses and because PLWH are a key target population for adult pneumococcal vaccination strategies.

Study design: STRIDE‑7 (phase 3)

Overview

STRIDE‑7 was a two‑part, international, phase 3, randomised, active comparator–controlled trial conducted at 20 centres across Belgium, Chile, France, South Africa, Thailand, and the USA. The trial enrolled adults aged ≥18 years living with HIV with CD4 counts ≥50 cells/μL, plasma HIV RNA <50 000 copies/mL, and who had been receiving combination ART for ≥6 weeks.

Randomisation and interventions

Part A was double‑blind and parallel‑group. Participants were randomised 1:1 to receive either:

– V116 (0.5 mL intramuscular) followed by placebo 8 weeks later; or

– PCV15 (0.5 mL intramuscular) followed 8 weeks later by PPSV23 (0.5 mL intramuscular).

Masking applied to the funder, site staff, data management team, and participants; unmasked personnel administered vaccines. Part B was an open‑label exploratory substudy in which participants who had received V116 in part A could later receive PCV15 after completion of part A follow‑up.

Endpoints and assays

The primary immunogenicity endpoint in part A (assessed in the per‑protocol population) was serotype‑specific opsonophagocytic activity geometric mean titres (OPA GMTs) measured 30 days post‑vaccination for the 13 serotypes common to V116 and PCV15/PPSV23, plus for the eight serotypes unique to V116. Blood samples were collected on day 1 (baseline), day 30, and at 12 weeks post‑vaccination in part A. Immunogenicity was summarized descriptively. Safety outcomes included solicited and unsolicited adverse events (AEs), injection‑site reactions, and serious adverse events (SAEs).

Key findings

Enrollment and baseline characteristics

Between July 13, 2022, and July 13, 2023, 313 adults were randomised in part A: 156 to V116 plus placebo and 157 to PCV15 plus PPSV23. Of these, 304 participants (97%) completed part A (152 in each group). Demographics were balanced: mean age 45 years (SD 13), 71% male, 29% female. Most participants were on ART and met eligibility HIV thresholds (CD4 ≥50 cells/μL and plasma HIV RNA <50 000 copies/mL). In part B, 126 of 155 (81%) participants in the V116 arm received PCV15 later (median interval 11.4 months, range 9.5–16.9) in an open‑label exploratory phase.

Immunogenicity

– V116 induced OPA responses against all 21 vaccine serotypes by day 30. The primary analysis comparing serotype‑specific OPA GMTs showed that, for the 13 serotypes common to V116 and the PCV15/PPSV23 comparator, responses at day 30 after V116 were generally similar to responses measured at week 12 after the PCV15→PPSV23 sequence.

– For the eight serotypes that are unique to V116, OPA responses at day 30 were higher than responses observed with the PCV15→PPSV23 comparator at the designated time points.

– Descriptive data from the study indicate robust serological responses across age and baseline CD4 strata included in the trial; full serotype‑specific GMTs and fold‑rise data are reported in the primary publication (Pathirana et al., Lancet HIV 2025).

Interpretation: These results suggest V116 provides broad serotype‑specific immunogenicity that is at least comparable to the PCV15→PPSV23 regimen for shared serotypes and superior for serotypes unique to V116 in this adult HIV population.

Safety and tolerability

– Overall AEs: fewer participants in the V116 plus placebo group experienced at least one AE compared with the PCV15 plus PPSV23 group (111/155 [72%] vs 141/155 [91%]).

– Injection‑site reactions: injection‑site AEs were reported in 79/155 (51%) participants in the V116 arm versus 130/155 (84%) in the PCV15→PPSV23 arm.

– Serious adverse events: SAEs were uncommon (four [3%] in the V116 arm vs six [4%] in the comparator arm); none were considered related to vaccination.

– Mortality: one death occurred in the V116 arm during part A; the cause was unknown and judged non‑vaccine‑related.

Overall, V116 demonstrated a favorable tolerability profile with fewer local and overall adverse events compared with the two‑dose PCV15→PPSV23 sequence.

Expert commentary and contextual interpretation

The STRIDE‑7 data provide clinically relevant information for vaccine selection in PLWH. Key considerations when interpreting these results:

– Immunogenicity versus clinical protection: STRIDE‑7 demonstrates immunogenicity (OPA responses), which are accepted surrogates for protection against vaccine‑type pneumococcal disease, but the trial was not designed to measure clinical efficacy against IPD or non‑bacteremic pneumonia. Observational or randomized effectiveness studies and post‑licensure surveillance will be needed to confirm vaccine effectiveness in PLWH.

– Broader serotype coverage: The inclusion of eight serotypes not present in PCV15 or some other adult PCVs may address residual disease attributable to adult‑predominant serotypes. Broader coverage could translate into meaningful incremental reductions in disease if those serotypes continue to circulate and cause clinical disease in adult populations.

– Safety and single‑dose strategy: The V116 regimen evaluated here was a single PCV dose followed by placebo at 8 weeks, unlike the comparator strategy that combined PCV15 with a subsequent PPSV23 dose. The lower frequency of injection‑site reactions and overall AEs with V116 is notable, and a single‑dose adult PCV strategy could simplify vaccination logistics for high‑risk adults; however, durability and breadth of long‑term protection require further study.

– Relevance to immunosuppressed subgroups: STRIDE‑7 enrolled PLWH with CD4 counts ≥50 cells/μL and on ART for ≥6 weeks. Data are limited for those with advanced immunosuppression (CD4 <50 cells/μL) or uncontrolled viraemia, populations that may have more attenuated responses and for whom timing and additional doses may need tailoring.

– Programmatic and epidemiological considerations: Introduction of an adult‑specific 21‑valent PCV could alter serotype epidemiology via direct protection and indirect effects; surveillance for serotype replacement and monitoring of disease burden are essential accompanying activities.

Limitations

– Immunogenicity surrogate endpoints: The trial measured OPA GMTs rather than clinical outcomes (IPD or pneumonia), so inference about real‑world protection is indirect.

– Population: The trial excluded individuals with profound immunosuppression (CD4 <50 cells/μL) and required recent ART; findings may not generalize to all PLWH, especially those with advanced disease or ART‑naïve status.

– Comparator regimen timing: The PCV15→PPSV23 schedule involves a second dose at 8 weeks; responses were compared across different post‑vaccination time points (day 30 for V116 vs week 12 for the comparator), which the investigators prespecified but still requires cautious interpretation.

– Short follow‑up for durability and rare events: Longer follow‑up and larger post‑licensure datasets will be necessary to evaluate durability of protection and rare adverse events.

Clinical and policy implications

– Vaccine choice for PLWH: STRIDE‑7 supports V116 as an immunogenic and well‑tolerated single‑dose PCV option for adults living with HIV, potentially offering broader serotype coverage than existing licensed adult PCVs.

– Implementation considerations: Decisions by national advisory committees (eg, ACIP in the USA) will consider STRIDE‑7 along with other immunogenicity, safety, epidemiology, cost‑effectiveness, and supply data. For clinicians, V116 may become an additional tool to protect adults at increased pneumococcal risk, but guidance will need to clarify recommended schedules, revaccination, and use in those with advanced immunosuppression.

– Research priorities: Key next steps include effectiveness studies in diverse settings, longer‑term immunogenicity and safety follow‑up in PLWH (including those with low CD4 counts), assessment of co‑administration with other adult vaccines, and surveillance for serotype replacement.

Conclusion

The STRIDE‑7 phase 3 trial demonstrates that V116, a 21‑valent adult‑specific pneumococcal conjugate vaccine, elicits robust OPA responses to all 21 vaccine serotypes and has a favorable tolerability profile in adults living with HIV. These data support consideration of V116 as a vaccine option for PLWH, particularly where broader serotype coverage could address residual adult pneumococcal disease burden. Confirmation of clinical effectiveness and long‑term safety, and guidance for use in severely immunosuppressed individuals, remain priorities.

Funding and trial registration

The trial was funded by MSD. STRIDE‑7 is registered at ClinicalTrials.gov (NCT05393037) and EudraCT (2021‑006710‑36). The primary report is Pathirana J, Ramgopal M, Martin C, et al.; STRIDE‑7 Study Group. 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. Lancet HIV. 2025 Oct;12(10):e679‑e690. doi: 10.1016/S2352‑3018(25)00165‑1. Epub 2025 Sep 12. PMID: 40953572