Ad26.COV2.S

A single administration of the candidate vaccine protected the experimental animals from severe clinical disease after high-dose intranasal SARS-CoV-2 infection.

Adenovirus 26 vector-based vaccine carrying the SARS-CoV-2 spike protein (GenBank: MN908947) optimized for stability as an immunogen elicited strong binding- and neutralizing antibody responses in mice.

Neutralizing-antibody titers against wild-type virus were detected in 90% or more of all participants on day 29 after the first vaccine dose. Spike-binding antibody responses were similar to neutralizing-antibody responses.

The vaccine elicited anti-Spike (full length; SARS-CoV-2), anti-RBD, and neutralizing antibodies in all vaccinated individuals by day 57. Boost immunization led to a more potent response. The observed antibody responses were of various Ig classes. Th1-biased T cell response was observed. Other immune responses were noted, as well. Sample size: 4 groups of 5 (different vaccine dosing) + 5 subjects placebo. Dosage: 1 or 2 intramuscular doses of 5×10^10 or 1×10^11 viral particles (If a single vaccine dose was administered, it was complemented by placebo in the second dose). Primary outcome: Immune response.

In non-human primates, a single dose vaccination induced neutralizing antibody response that lasted at least 14 weeks. Two dose regimen elicited higher peak binding and neutralizing antibody responses. T helper cell response was CD4+ Th1-skewed, Spike-specific CD8+ T cells produced mainly IFN-γ and IL-2. The vaccine (in either regimen) provided near complete lower respiratory tract protection and significant upper respiratory tract protection in non-human primates in a viral challenge 3 months post vaccination. Neutralization of the B.1.351. variant was lower, whereas the vaccine retained its efficacy in B.1.1.7 strain neutralization.

The sera of the majority of individuals who were previously vaccinated with Ad26.COV2.S and have recently received a booster dose of an mRNA vaccine were capable of Delta and Omicron variants’ (pseudoviruses’) neutralization in vitro. The neutralization was generally less potent against the Delta variant and even less potent against the Omicron variant, compared to the wild type. Previous infection mostly increased neutralization even in individuals without a booster; although, it was generally low. The antibody protection decreased with time past from the vaccination. Sample size: 20 (recent vaccination) + 6 (distant vaccination) + 6 (convalescent and distant vaccination) + 8 (with a booster). Main outcome: 1 or 2 doses (2nd mostly an mRNA vaccine).

IgG antibodies from sera of vaccinated human individuals protected experimental animals from weight loss in a viral challenge. The antibodies displayed Spike binding and SARS-CoV-2 pseudovirus neutralization in vitro. 

A decrease was observed in convalescent serum’s capacity to neutralize the Omicron strain of SARS-CoV-2 compared to the D614G strain. It retained some neutralization capacity, however.