Ability of SpikoGen®, an Advax‐CpG adjuvanted recombinant spike protein vaccine, to induce cross‐neutralising antibodies against SARS‐CoV‐2 variants

Abstract SpikoGen® vaccine is a subunit COVID‐19 vaccine expressed in insect cells comprising recombinant spike protein extracellular domain formulated with Advax‐CpG55.2™ adjuvant. A Phase 2 trial was conducted in 400 adult participants randomised 3:1 to receive two intramuscular doses of SpikoGen® vaccine or saline placebo 3 weeks apart. Some Phase 2 trial participants later enrolled in a separate booster study and received a third dose of SpikoGen® vaccine. This stored serum was used to assess the ability of SpikoGen® vaccine to induce cross‐neutralising antibodies against SARS‐CoV‐2 variants of concern. Sera taken at baseline and 2 weeks after the second vaccine dose from baseline seronegative Phase 2 subjects was evaluated using a panel of spike pseudotype lentivirus neutralisation assays for the ability to cross‐neutralise a wide range of SARS‐CoV‐2 variants, including Omicron BA.1, BA.2 and BA.4/5. Stored samples of subjects who participated in both the 2‐dose Phase 2 trial and a third dose booster trial 6 months later were also analysed for changes in cross‐neutralising antibodies over time and dose. Two weeks after the second dose, sera broadly cross‐neutralised most variants of concern, albeit with titres against Omicron variants being ~10‐fold lower. While Omicron titres fell to low levels 6 months after the second vaccine dose in most subjects, they showed a ~20‐fold rise after the third dose booster, after which there was only a ~2‐3‐fold difference in neutralisation of Omicron and the ancestral strains. Despite being based on the ancestral Wuhan sequence, after two doses, SpikoGen® vaccine induced broadly cross‐neutralising serum antibodies. Titres then reduced over time but were rapidly restored by a third dose booster. This resulted in high neutralisation including against the Omicron variants. This data supports ongoing use of SpikoGen® vaccine for protection against recent SARS‐CoV‐2 Omicron variants.