Neutralizing antibodies to SARS‐CoV‐2 Omicron variant after third mRNA vaccination in health care workers and elderly subjects

Abstract

The emergence of SARS-CoV-2 Omicron variant (B.1.1.529) with major spike protein mutations has raised concern over potential neutralization escape and breakthrough infections among vaccinated and previously SARS-CoV-2-infected subjects. We measured crossprotective antibodies against variants in health care workers (HCW, n = 20) and nursing home residents (n = 9) from samples collected at 1-2 months, following the booster (3rd) dose. We also assessed the antibody responses in subjects infected before the Omicron era (n = 38) with subsequent administration of a single mRNA vaccine dose. Following booster vaccination, HCWs had high IgG antibody concentrations to the spike protein and neutralizing antibodies (NAb) were detectable against all variants. IgG concentrations among the elderly remained lower, and some lacked NAbs against the Beta and Omicron variants. NAb titers were significantly reduced against Delta, Beta, and Omicron compared to WT virus regardless of age. Vaccination induced high IgG concentrations and variable titers of cross-reactive NAbs in previously infected subjects, whereas NAb titers against Omicron were barely detectable 1 month postinfection. High IgG concentrations with cross-protective neutralizing activity were detected after three Coronavirus Disease 2019 (COVID-19) vaccine doses in HCWs. However, lower NAb titers seen in the frail elderly suggest inadequate protection against Omicron breakthrough infections, yet protection against severe COVID-19 is expected.

Neutralising antibody responses to SARS-CoV-2 omicron among elderly nursing home residents following a booster dose of BNT162b2 vaccine: A community-based, prospective, longitudinal cohort study

“…The neutralisation capacity of sera from vaccinated or previously infected (i.e., convalescent) individuals against the omicron (B.1.1.529) (BA.1) variant of SARS-CoV-2 has been well studied among several population groups, and has been shown to be lower against omicron compared to other variants. 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 Information on the vaccine efficacy and the neutralisation capacity of sera from elderly individuals against omicron is more limited, 13 , 14 , 15 , 16 despite decreased immunogenicity, increased risk of severe forms of disease and accelerated waning of immunity in this population. 17 , 18 , 19 Here, we evaluated the capacity of a booster dose of BNT162b2 to elicit neutralising antibodies against omicron BA.1 and examined levels of humoral immunity before omicron breakthrough infections among residents living in nursing homes.…”

T‐cell responses to SARS‐CoV‐2 Omicron spike epitopes with mutations after the third booster dose of an inactivated vaccine

“…The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) variant of concern Omicron (B.1.1.529), which has more than 30 mutations in the spike protein, has raised an alarm related to the control of coronavirus disease 2019. 1 , 2 , 3 , 4 , 5 Recent data have shown that the induction of a neutralizing antibody response against the Omicron variant by either vaccines or infection is drastically reduced, 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 while T‐cell responses are largely preserved. 5 , 13 , 14 , 15 , 16 The T‐cell response to the Omicron variant is based on dozens of peptide epitopes; several groups have performed computational analyses and found that even for the Omicron strain with more than 30 mutations, ~80% of the antigenic peptides recognized by T cells are identical to those of original ancestral strain.…”

A Review on Immunological Responses to SARS-CoV-2 and Various COVID-19 Vaccine Regimens

“…Moreover, a study has been conducted on the health care workers, who received a third dose (booster) following 6-9 months of the second dose. It has been reported that crossprotective neutralizing antibodies were present against the Omicron and other variants of SARS-CoV-2 in the individuals vaccinated with Comirnaty, but the titer of these antibodies was less in Comirnaty vaccinated individuals compared to individuals vaccinated with Spikevax [77,78]. Moreover, the cellular response against SARS-CoV-2 has also been roughly estimated and it was observed that in 95.2% of the participants RBD-specific CD4+ T cell lymphocytes were activated and the magnitude of this T cell response was directly proportional to the GMC of the anti-RBD antibodies and the GMT of NA.…”

“…However, neutralization GMT against SARS-CoV-2 Beta mutant with three mutations (E484K + N501Y + D614G) was less in comparison to that against the N501Y mutant or Alpha mutant with three mutations (69/70 deletion + N501Y + D614G) [74]. Apart from these variants, WHO recognized Omicron as the variant of concern, hence it is crucial to develop a vaccine against this particular variant as it is distantly related to the previously reported variants [77]. Moreover, a study has been conducted on the health care workers, who received a third dose (booster) following 6-9 months of the second dose.…”

“…Moreover, the efficacy and safety of this vaccine candidate were confirmed to be 94.1% [83]. Moreover, when the third dose of this vaccine was administered as a booster dose to the health care workers, 6 to 9 months after the second dose, the spikevax has been reported to be effective against Omicron, and other variants of SARS-CoV-2, and the concentration of the cross-neutralizing antibodies were higher in individuals vaccinated with Spikevax, compared to that of the Comirnaty vaccinated individuals [77,84].…”