Recombinant respiratory syncytial vrus vaccine(Beijing Advaccine Biotechnology Co., Ltd.)

Background: Respiratory syncytial virus (RSV) poses a significant global health threat, particularly to children and the elderly. While progress has been made in RSV vaccine development, gaps remain, especially in protecting the elderly population. BARS13, a recombinant non-glycosylated G protein-based RSV vaccine, has shown promise in preclinical and Phase 1 studies. This phase II trial sought to determine whether escalating doses of BARS13 could enhance immune responses while maintaining safety and tolerability in healthy older adults aged 60–80 years. Methods: This study employed a rigorous randomized, double-blind, placebo-controlled design involving 125 participants across two Australian centers. Participants were randomized in a 3:1 (vaccine–placebo) ratio for Cohorts 1–2 (30 active, 10 placebo each) and a 2:1 ratio for Cohort 3 (30 active, 15 placebo). Cohort 1 (low dose) received 10 µg rRSV-G + 10 µg CsA in one arm + a placebo in the other (Days 1 and 29); Cohort 2 (high dose) received 10 µg rRSV-G + 10 µg CsA in both arms (20 µg total per dose, Days 1 and 29); Cohort 3 (multi-dose) received the same dose as that of Cohort 2 but with a third dose on Day 57. The placebo groups received IM injections in both arms at matching timepoints. The primary endpoints included safety and tolerability assessments, while the secondary endpoints evaluated the RSV G protein-specific IgG antibody concentrations using enzyme-linked immunosorbent assays (ELISAs). Statistical analysis was performed on both the safety and immunogenicity populations. Results: BARS13 was well-tolerated across all cohorts, with no serious adverse events (SAEs) related to the vaccine. The most common adverse events were mild local reactions (pain and tenderness) and systemic reactions (headache and fatigue), which resolved within 24–48 h. Immunogenicity analysis demonstrated a dose-dependent increase in the RSV G protein-specific IgG geometric mean concentrations (GMCs). Cohort 3, which received multiple high-repeat dose administrations, showed the highest immune response, with the IgG GMC rising from 1195.4 IU/mL on Day 1 to 1681.5 IU/mL on Day 113. Response rates were also the highest in Cohort 3, with 86.2% of participants showing an increase in antibody levels by Day 29. Conclusions: BARS13 demonstrated a favorable safety profile and strong immunogenicity in elderly participants, with a clear dose-dependent antibody response. These results support further development of BARS13 as a potential RSV vaccine candidate for the elderly. Further studies are needed to evaluate the long-term efficacy and optimal dosing schedule.

Background: With the enormous morbidity and mortality caused by respiratory syncytial virus (RSV) infections among infants and the elderly, vaccines against RSV infections are in large market demand. Methods: We conducted a first-in-human (FIH), randomized, double-blind, placebo-controlled dose escalation study to evaluate the safety and immunogenicity response of the rRSV vaccine (BARS13) in healthy adults aged 18–45. A total of 60 eligible participants were randomly assigned to receive one of four dose levels or vaccination regimens of BARS13 or placebo at a 4:1 ratio. Results: The mean age was 27.40, and 23.3% (14/60) were men. No treatment-emergent adverse events (TEAEs) led to study withdrawal within 30 days after each vaccination. No serious adverse event (SAE) was reported. Most of the treatment-emergent adverse events (TEAEs) recorded were classified as mild. The high-dose repeat group had a serum-specific antibody GMC of 885.74 IU/mL (95% CI: 406.25–1931.17) 30 days after the first dose and 1482.12 IU/mL (706.56–3108.99) 30 days after the second dose, both higher than the GMC in the low-dose repeat group (885.74 IU/mL [406.25–1931.17] and 1187.10 IU/ mL [610.01–2310.13]). Conclusions: BARS13 had a generally good safety and tolerability profile, and no significant difference in terms of adverse reaction severity or frequency was observed between different dose groups. The immune response in repeat-dose recipients shows more potential in further study and has guiding significance for the dose selection of subsequent studies.