Omicron spike function and neutralizing activity elicited by a comprehensive panel of vaccines

Abstract

The SARS-CoV-2 Omicron variant of concern comprises several sublineages with BA.2 and BA.2.12.1 having replaced the previously dominant BA.1, and BA.4 and BA.5 increasing in prevalence worldwide. We show that the large number of Omicron sublineage spike mutations lead to enhanced ACE2 binding, reduced fusogenicity, and severe dampening of plasma neutralizing activity elicited by infection or seven clinical vaccines relative to the ancestral virus. Administration of a homologous or heterologous booster based on the Wuhan-Hu-1 spike sequence markedly increased neutralizing antibody titers and breadth against BA.1, BA.2, BA.2.12.1, and BA.4/5 across all vaccines evaluated. Our data suggest that although Omicron sublineages evade polyclonal neutralizing antibody responses elicited by primary vaccine series, vaccine boosters may provide sufficient protection against Omicron-induced severe disease.

SARS-CoV-2 Omicron BA.5: Evolving tropism and evasion of potent humoral responses and resistance to clinical immunotherapeutics relative to viral variants of concern

“… 24 Using clinical isolates, we confirm findings from early seminal contributions. 25 , 26 , 27 , 28 , 29 , 30 Observations using pseudovirus have seen greater antibody evasion of BA.5 compared to its parent BA.2 following different vaccine schedules. Importantly herein, we observe the peak responses following three doses of BNT162b2 to generate antibody neutralising breadth to equally cover BA.2 and BA.5 and this is consistent with that recently observed by Bowen and colleagues.…”

Cellular and humoral immunity towards parental SARS-CoV-2 and variants of concern after two doses of the NVX-CoV2373-vaccine in comparison to homologous BNT162b and mRNA1273 regimens

“…Regarding neutralizing activity, a third booster dose after NVX-CoV2373 may seem equally valuable to improve protection as has been shown for other primary vaccine regimens [26-28]. This is supported by promising data from a small study showing that neutralizing antibody titers towards VOCs increased in all seven NVX-CoV2373-vaccinated individuals who either received mRNA-1273, BNT162b2 or Ad26.COV.2 as a booster dose [29].…”

“…The immunogenicity of the two mRNA vaccines has been extensively characterized in real world settings, and both vaccines induce strong antibody and T-cell responses [8,9]. Likewise, the phase 1-2 trial of the NVX-CoV2373 vaccine or a recent phase III trial has shown induction of high antibody titers [10,11], and first data on neutralizing activity towards SARS-CoV-2 variants of concern (VOCs) from participants of the pivotal trial 3-4 months after the second dose became available recently [12][13][14]. However, real world data on the immunogenicity of the NVX-CoV2373 vaccine during the induction phase, especially regarding its ability to induce CD4 and CD8 T cells and in comparison to other licensed vaccines are currently lacking.…”

Time to redefine a primary vaccination series?

“… 5 Moreover, a longer interval (4 months) between the two doses of Ad26.COV2.S led to lesser omicron immune escape than other two-dose vaccine regimens (given 3–4 weeks apart). 6 However, vaccinees receiving two doses of Ad26.COV2.S had greater omicron immune escape than vaccinees receiving three doses of mRNA vaccines or three doses of different heterologous regimens. These findings suggest that a third dose of either Ad26.COV2.S or another vaccine might act as a booster dose for a two-dose regimen of Ad26.COV2.S.…”