Post-Hoc Analysis of Potential Correlates of Protection of a Recombinant SARS-CoV-2 Spike Protein Extracellular Domain Vaccine Formulated with Advax-CpG55.2-Adjuvant

Abstract

SpikoGen^® vaccine is a subunit COVID-19 vaccine composed of an insect cell expressed recombinant spike protein extracellular domain formulated with Advax-CpG55.2™ adjuvant. A randomized double-blind, placebo-controlled Phase II clinical trial was conducted in 400 adult subjects who were randomized 3:1 to receive two intramuscular doses three weeks apart of either SpikoGen^® vaccine 25 μg or saline placebo, as previously reported. This study reports a post hoc analysis of the trial data to explore potential immune correlates of SpikoGen^® vaccine protection. A range of humoral markers collected pre- and post-vaccination, including spike- and RBD-binding IgG and IgA, surrogate (sVNT), and conventional (cVNT) virus neutralization tests were compared between participants who remained infection-free or got infected over three months of follow-up. From 2 weeks after the second vaccine dose, 21 participants were diagnosed with SARS-CoV-2 infection, 13 (4.2%) in the SpikoGen^® group and 8 (9%) in the placebo group. Those in the vaccinated group who experienced breakthrough infections had significantly lower sVNT titers (GMT 5.75 μg/mL, 95% CI; 3.72-8.91) two weeks after the second dose (day 35) than those who did not get infected (GMT 21.06 μg/mL, 95% CI; 16.57-26.76). Conversely, those who did not develop SARS-CoV-2 infection during follow-up had significantly higher baseline sVNT, cVNT, spike-binding IgG and IgA, and RBD-binding IgG, consistent with a past SARS-CoV-2 infection. SpikoGen^® further reduced the risk of re-infection (OR 0.29) in baseline seropositive (previously infected) as well as baseline seronegative participants. This indicates that while SpikoGen vaccine is protective in seronegative individuals, those with hybrid immunity have the most robust protection.

Keywords: Advax; COVID-19; CpG; SARS-CoV-2; adjuvant; correlate; protection; vaccine.

Figure 1

Kaplan Meir curve showing cumulative SARS-CoV-2 infections in SpikoGen^® and placebo groups. Black down arrows indicate the timing of the first and second vaccine or placebo dose. The dotted line represents two weeks post-second dose, the normal point from which infections counting towards COVID-19 vaccine efficacy are accrued.

Figure 2

Baseline (Day 0) spike antibody levels (serum S1-binding IgG (A), S1-binding IgA (B), and surrogate virus neutralization test (sVNT) (C)) in participants who subsequently either did or did not have a documented SARS-CoV-2 infection during 3 months of follow-up. Mean plus standard deviation. The horizontal dotted line on each figure indicates the seropositive cutoff of each assay.

Figure 3

Spike antibody levels (serum S1-binding IgG (A), S1-binding IgA (B), and surrogate virus neutralization test (sVNT) (C)) measured two weeks after the 2nd SpikoGen^® or placebo dose (Day 35) in participants who subsequently either did or did not have a documented SARS-CoV-2 infection during 3 months of follow-up. Mean plus standard deviation. The horizontal dotted line on each figure indicates the seropositive cutoff of each assay.