A Phase 2 random, double-blind, placebo-controlled study of the safety and immunogenicity of a recombinant G protein-based respiratory syncytial virus vaccine in healthy older adults

Abstract

ABSTRACTBackgroundRespiratory syncytial virus (RSV) is an important cause of disease in older adults. Vaccines against RSV infections and respiratory diseases are in large market demand. Although there are currently two licensed RSV-based pre-F antigen vaccines available for older adults, no G antigen-based RSV vaccine is authorized. This phase 2 study aimed to evaluate the safety and immunogenicity of a recombinant G protein-based RSV vaccine in this population.MethodsA phase-2 randomized, double-blind, placebo-controlled, dose-ranging study was conducted to evaluate the safety, tolerability and immunogenicity of the BARS13 (rRSV G protein with CsA) when administered by an intramuscular (IM) injection to healthy participants 60 to 80 years old. A total of 125 eligible participants were randomized in a 3:1 ratio (vaccine versus placebo) for Cohorts 1 and 2 and randomized in a 2:1 ratio for Cohort 3 to receive one of the three treatment regimens or placebo.ResultsThe average age was 65.3, and 50.4% (63/125) were men. Until the interim analysis (4 weeks following the last vaccination), no treatment-related SAE occurred. TEAEs did not increase with vaccination dosage or frequency. All adverse effects were mild or moderate, not severe or life-threatening. BARS13 vaccination increased IgG anti-RSV antibody levels in all cohorts, but higher doses and frequency boosted immune responses significantly. The high-dose thrice-administered recipients had serum-specific IgG antibody GMC of 881.0 IU/mL (95% CI: 794.5-1473.4) before the first dose (Week 0), 1116.3 IU/mL (95% CI:990.7-1772.5) 4 weeks after the first dose (Week 4), 1309.4IU/mL (95% CI: 1162.8-2041.5) 4 weeks after the second dose (Week 8), and1359.6 IU/mL (95% CI: 1197.9-2525.7) 4 weeks after the third dose (Week 12). For the low-dose twice-administered recipients, 84% responded at 4 weeks after the first immunization (Week 4) and 83.3% at 4 weeks after the second (Week 8). The high-dose twice-administered recipients had 95.5% response at 4 weeks after the first immunization (Week 4) and 72.2% at 4 weeks after the second (Week 8). At Week 4, 85.7% of high-dose thrice-administered recipients responded, 85.2% at Week 8, and 79.2% at Week 12.ConclusionsThe study demonstrates the safety and tolerability of BARS13 across different dose groups. Adverse reactions were not significantly different among participants receiving varying doses of BARS13. Levels of anti-G antibodies exhibited a dose- and frequency-dependent responses in the older population. The continuous upward trend in antibody concentration up to the interim analysis is promising for the effectiveness of BARS13.