Safety and Immunogenicity of a Severe Acute Respiratory Syndrome Coronavirus 2 Spike Subunit Vaccine Stabilized in the Prefusion Conformation by a Second-Generation Molecular Clamp and Evaluated in Adults Aged 18-55 Years: A Randomized, Double-Blind, Active Comparator, Phase I Trial.

BACKGROUND:A coronavirus disease 2019 (COVID-19) subunit vaccine developed with the molecular clamp platform was among the first to enter clinical trials in 2020. While the vaccine was well suited to large-scale manufacture and demonstrated a favorable safety and immunogenicity profile, it did not progress into further clinical testing due to the human immunodeficiency virus 1 (HIV-1)-derived sequence in the molecular clamp, interfering with certain point-of-care HIV-1 diagnostic tests. A second-generation molecular clamp (MC2) has since been developed. Here, we describe a phase I clinical trial of an MC2-stabilized severe acute respiratory syndrome coronavirus (SARS-CoV-2) spike subunit vaccine, UQSC2. METHODS:A phase I, double-blind, active comparator-controlled trial was conducted in Australia (ClinicalTrials.gov NCT05775887). Healthy adults (aged 18-50 years), who had previously received ≥3 doses of an approved messenger RNA SARS-CoV-2 vaccine, received a single booster dose of either UQSC2 or the approved comparator NVX-CoV2373 (Nuvaxovid; Novavax) (n = 70; 35 per group). Safety, humoral immunogenicity (including against virus variants), and cellular immunogenicity were assessed through day 183. Cases of confirmed coronavirus disease 2019 (COVID-19) infection during the study were also examined. RESULTS:Both vaccines were equally well tolerated and elicited comparable increases in neutralizing humoral responses against the vaccine-matched prototypic, Wuhan strain of SARS-CoV-2. CONCLUSIONS:UQSC2 was as well tolerated as the authorized comparator vaccine and produced an equally robust boost in neutralizing immune response. These findings support the effectiveness of the MC2 platform in producing vaccines against newly emerging variants of SARS-CoV-2 and other respiratory viruses, as well as the platform's potential use in emergency response to novel viruses.