1955. Immunogenicity And Safety of a Virus-Like Particle (VLP) Protein Subunit SARS-CoV-2 Vaccine in Adults: a Phase 1/2 Study

Abstract

Abstract Background COVID-19 continues to cause substantial morbidity and mortality globally. It is likely that booster vaccinations will be needed in future years to protect older adults and those with chronic medical conditions. We present interim topline results of a phase 1/2 study of IVX-411 [ACTRN12621000738820.; ACTRN12621000882820], an investigational VLP protein subunit SARS-CoV-2 vaccine, in adults aged 18–69 years (Figure 1). Methods In Part 1, 84 SARS-CoV-2-naïve adults were randomized to receive two doses on Days 0 and 28 of either IVX-411 (5, 25, or 125µg) ± adjuvant, or placebo (Figure 2a). In Part 2, 84 subjects received a single dose of either IVX-411 ± adjuvant or placebo 3–6 months after completion of a primary licensed vaccine regimen (Figure 2b). Solicited adverse events (AEs) were collected for 7 days after each dose, with immunogenicity assessed on Days 0, 28, and 49 [(Part 1) and on Days 0, 7 and 28 (Part 2). Primary outcomes in both parts were solicited and unsolicited AEs, neutralizing antibody titers, and spike protein-specific IgG antibody titers. Results Demographics were similar in the IVX-411 groups vs placebo. In Part 1 and Part 2, local reactogenicity was mild-to-moderate, with higher rates of AEs with increasing doses and addition of adjuvant (Figure 3a). Rates of systemic AEs were similar to placebo across groups (Figure 3b). No vaccine-related severe or serious AEs were noted. IVX-411 was immunogenic in both primary and booster vaccination: in SARS-CoV-2-naïve subjects, a limited dose effect was seen, with significantly higher antibody titers in the groups receiving adjuvanted IVX-411 vaccine (p< 0.01; Figure 4a). The magnitude of antibody responses was similar to, or below, Human Convalescent Sera levels. In previously vaccinated subjects, IVX-411 boosted baseline antibody titers, with no conclusive dose or adjuvant effect (Figure 4b). Immunogenicity was observed across all variants of concern (beta, delta, and omicron) in both parts, with up to 7- fold rises from baseline (Figure 5). Conclusion The study met all primary safety and immunogenicity objectives, with acceptable tolerability profiles in primary and booster vaccination. A clear adjuvant effect was observed in SARS-CoV-2-naïve subjects. Disclosures All Authors: No reported disclosures.