Immunogenicity and safety of SARS-COV-2 recombinant protein subunit vaccine (INDOVAC) in west Sumatera Province adolescents: A phase 3, observer blind, randomized, active-controlled

Background PT Bio Farma (Persero), an Indonesian state-owned pharmaceutical company, developed IndoVac, a recombinant protein subunit vaccine for active immunization against SARS-CoV-2. IndoVac is based on the RBD of the spike protein of the ancestral Wuhan-Hu-1 SARS-CoV-2 strain. Each 0.5-mL dose contains 25 μg of recombinant SARS-CoV-2 RBD protein, 750 μg of AlOH, 750 μg of CpG 1018 as an adjuvant, 2.226 mg of NaCl, and 0.923 mg of tris(hydroxymethyl)aminomethane. This phase 3 study evaluated the immunogenicity and safety of IndoVac in adolescents aged 12–17 years in West Sumatra Province, Indonesia, using Covovax as an active comparator. Methods We conducted an observer-blind, randomized, active-controlled trial. Participants with no previous COVID-19 vaccination received two doses of IndoVac or Covovax 28 days apart and were followed for 12 months after the second dose. The primary immunogenicity endpoint was the geometric mean ratio (GMR) of neutralizing antibodies against circulating Omicron variants at Day 14 after the second dose. Seropositivity, seroconversion, anti-RBD IgG responses, antibody persistence, and safety were assessed. Results A total of 649 participants were enrolled between 9 October and 22 November 2022, received at least one dose of the study vaccine. The GMR of neutralizing antibodies against the circulating Omicron variant at 14 days after the second dose was 1.18 (95% CI, 1.14–1.20), meeting the World Health Organization (WHO) non-inferiority criterion for immunobridging (95% CI lower bound >0.67). Neutralizing antibody levels were maintained for up to 12 months after the second dose. No serious adverse events (SAEs) were considered possibly, probably, or likely related to vaccination. Conclusions IndoVac was well tolerated and elicited a non-inferior neutralizing antibody response compared with Covovax. Despite being based on ancestral Wuhan-Hu-1 strain, IndoVac generated cross-reactive neutralizing responses against circulating Omicron variants, with humoral responses persisting for 12 months after the second dose.