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[Preprint]. 2022 Mar 16:2022.03.15.484542.
doi: 10.1101/2022.03.15.484542.

Omicron BA.1 and BA.2 neutralizing activity elicited by a comprehensive panel of human vaccines

John E Bowen  1 , Kaitlin R Sprouse  1 , Alexandra C Walls  1   2 , Ignacio G Mazzitelli  3 , Jennifer K Logue  4 , Nicholas M Franko  4 , Kumail Ahmed  5 , Asefa Shariq  5 , Elisabetta Cameroni  6 , Andrea Gori  7   8   9 , Alessandra Bandera  7   8   9 , Christine M Posavad  10 , Jennifer M Dan  11   12 , Zeli Zhang  11 , Daniela Weiskopf  11 , Alessandro Sette  11   12 , Shane Crotty  11   12 , Najeeha Talat Iqbal  5 , Davide Corti  6 , Jorge Geffner  3 , Renata Grifantini  13 , Helen Y Chu  4 , David Veesler  1   2
Affiliations

Omicron BA.1 and BA.2 neutralizing activity elicited by a comprehensive panel of human vaccines

John E Bowen et al. bioRxiv. .

Update in

  • Omicron spike function and neutralizing activity elicited by a comprehensive panel of vaccines.
    Bowen JE, Addetia A, Dang HV, Stewart C, Brown JT, Sharkey WK, Sprouse KR, Walls AC, Mazzitelli IG, Logue JK, Franko NM, Czudnochowski N, Powell AE, Dellota E Jr, Ahmed K, Ansari AS, Cameroni E, Gori A, Bandera A, Posavad CM, Dan JM, Zhang Z, Weiskopf D, Sette A, Crotty S, Iqbal NT, Corti D, Geffner J, Snell G, Grifantini R, Chu HY, Veesler D. Bowen JE, et al. Science. 2022 Aug 19;377(6608):890-894. doi: 10.1126/science.abq0203. Epub 2022 Jul 19. Science. 2022. PMID: 35857529 Free PMC article.

Abstract

The SARS-CoV-2 Omicron variant of concern comprises three sublineages designated BA.1, BA.2, and BA.3, with BA.2 steadily replacing the globally dominant BA.1. We show that the large number of BA.1 and BA.2 spike mutations severely dampen plasma neutralizing activity elicited by infection or seven clinical vaccines, with cross-neutralization of BA.2 being consistently more potent than that of BA.1, independent of the vaccine platform and number of doses. Although mRNA vaccines induced the greatest magnitude of Omicron BA.1 and BA.2 plasma neutralizing activity, administration of a booster based on the Wuhan-Hu-1 spike sequence markedly increased neutralizing antibody titers and breadth against BA.1 and BA.2 across all vaccines evaluated. Our data suggest that although BA.1 and BA.2 evade polyclonal neutralizing antibody responses, current vaccine boosting regimens may provide sufficient protection against Omicron-induced disease.

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Figures

Figure 1.
Figure 1.. SARS-CoV-2 Omicron BA.1 and BA.2 evade human plasma neutralizing antibodies elicited by infection or primary vaccine series.
Plasma neutralizing antibody titers elicited by primary COVID-19 vaccination determined using SARS-CoV-2 spike VSV pseudotypes using VeroE6-TMPRSS2 as target cells. Individual points are representative geometric mean titers from two independent experiments consisting of two replicates each. Bars represent geometric means and error bars represent geometric standard deviations for each group. Statistical significance between groups of paired data was determined by Wilcoxon rank test and *p< 0.05, **p< 0.01, ***p< 0.001, ****p< 0.0001. Patient demographics are shown in Table S2. Normalized curves and fits are shown in Figure S1.
Figure 2.
Figure 2.. Booster doses rescue neutralization potency against Omicron BA.1 and BA.2.
Plasma neutralizing antibody titers elicited by COVID-19 vaccine boosters determined using SARS-CoV-2 S VSV pseudotypes and VeroE6-TMPRSS2 as target cells. Individual points are representative geometric mean titers from two independent experiments consisting of two replicates each. Bars represent geometric means and error bars represent geometric standard deviations for each group. Statistical significance between groups of paired data was determined by Wilcoxon rank test and *p< 0.05, **p< 0.01, ***p< 0.001, ****p< 0.0001. Patient demographics are shown in Table S2. Normalized curves and fits are shown in Figure S2.
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