Neutralization and durability of 2 or 3 doses of the BNT162b2 vaccine against Omicron SARS-CoV-2

Xia, Hongjie; Zou, Jing; Kurhade, Chaitanya; Cai, Hui; Yang, Qi; Cutler, Mark; Cooper, David A.; Muik, Alexander; Jansen, Kathrin U.; Xie, Xuping; Swanson, Kena A.; Shi, Pei–Yong

doi:10.1016/j.chom.2022.02.015

Cited by 89 publications

(79 citation statements)

References 15 publications

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“…2 Compared with the BA.1 and BA.2 sublineages, the prevalence of BA.3 has remained low, with a total of 613 BA.3 sequences in the GISAID database (https://www.gisaid.org/) as of March 12, 2022. Recent studies showed that BA.1 evades vaccine- and non-Omicron infection-elicited neutralization, 3,4 which, together with increased transmissibility, may partially account for the variant replacement from the previous Delta to the current Omicron. Since BA.1, BA2, and BA.3 have distinct sets of mutations in their spike glycoproteins ( Fig.…”

Section: Main Textmentioning

confidence: 99%

“…Using a panel of human sera collected at 1 month post dose 3 (PD3) of BNT162b2 vaccine 3 ( Fig. S3 ), we determined the 50% fluorescent focus-reduction neutralization titers (FFRNT 50 ) against recombinant USA-WA1/2020 and Omicron sublineage-spike mNG SARS-CoV-2s.…”

Section: Main Textmentioning

confidence: 99%

“…S3 ), we determined the 50% fluorescent focus-reduction neutralization titers (FFRNT 50 ) against recombinant USA-WA1/2020 and Omicron sublineage-spike mNG SARS-CoV-2s. We chose the PD3 sera, rather than post dose 2 sera, because (i) two doses of BNT162b2 did not elicit robust neutralization against Omicron BA.1 3 and (ii) many individuals have already received 3 doses of BNT162b2. The PD3 sera neutralized USA-WA1/2020, BA.1-, BA.2-, and BA.3-spike mNG viruses with geometric mean titers (GMTs) of 1211, 336, 300, and 190, respectively ( Fig.…”

Section: Main Textmentioning

confidence: 99%

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Neutralization of Omicron BA.1, BA.2, and BA.3 SARS-CoV-2 by 3 doses of BNT162b2 vaccine

Kurhade

Zou

Xia

et al. 2022

Preprint

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The newly emerged Omicron SARS-CoV-2 has 3 distinct sublineages: BA.1, BA.2, and BA.3. BA.1 accounts for the initial surge and is being replaced by BA.2, whereas BA.3 is at a low prevalence at this time. Here we report the neutralization of BNT162b2-vaccinated sera (collected at 1 month after dose 3) against the three Omicron sublineages. To facilitate the neutralization testing, we engineered the complete BA.1, BA.2, or BA.3 spike into an mNeonGreen USA-WA1/2020 SRAS-CoV-2. All BNT162b2-vaccinated sera neutralized USA-WA1/2020, BA.1-, BA.2-, and BA.3-spike SARS-CoV-2s with titers of >20; the neutralization geometric mean titers (GMTs) against the four viruses were 1211, 336, 300, and 190, respectively. Thus, the BA.1-, BA.2-, and BA.3-spike SARS-CoV-2s were 3.6-, 4.0-, and 6.4-fold less efficiently neutralized than the USA-WA1/2020, respectively. Our data have implications in vaccine strategy and understanding the biology of Omicron sublineages.

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confidence: 99%

Section: Main Textmentioning

confidence: 99%

Section: Main Textmentioning

confidence: 99%

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Neutralization of Omicron BA.1, BA.2, and BA.3 SARS-CoV-2 by 3 doses of BNT162b2 vaccine

Kurhade

Zou

Xia

et al. 2022

Preprint

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“…Serologic data indicate that antibody responses to Omicron can be at least partially boosted in the short-term (up to ~1 month) after a 3 rd vaccine dose (22)(23)(24)(25), suggesting that immunological memory generated by 2-dose vaccination has some reactivity against the Omicron Spike protein.…”

Section: Introductionmentioning

confidence: 99%

Efficient recall of Omicron-reactive B cell memory after a third dose of SARS-CoV-2 mRNA vaccine

Goel

Painter

Lundgreen

et al. 2022

Preprint

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Despite a clear role in protective immunity, the durability and quality of antibody and memory B cell responses induced by mRNA vaccination, particularly by a 3rd dose of vaccine, remains unclear. Here, we examined antibody and memory B cell responses in a cohort of individuals sampled longitudinally for ~9-10 months after the primary 2-dose mRNA vaccine series, as well as for ~3 months after a 3rd mRNA vaccine dose. Notably, antibody decay slowed significantly between 6- and 9-months post-primary vaccination, essentially stabilizing at the time of the 3rd dose. Antibody quality also continued to improve for at least 9 months after primary 2-dose vaccination. Spike- and RBD-specific memory B cells were stable through 9 months post-vaccination with no evidence of decline over time, and ~40-50% of RBD-specific memory B cells were capable of simultaneously recognizing the Alpha, Beta, Delta, and Omicron variants. Omicron-binding memory B cells induced by the first 2 doses of mRNA vaccine were boosted significantly by a 3rd dose and the magnitude of this boosting was similar to memory B cells specific for other variants. Pre-3rd dose memory B cell frequencies correlated with the increase in neutralizing antibody titers after the 3rd dose. In contrast, pre-3rd dose antibody titers inversely correlated with the fold-change of antibody boosting, suggesting that high levels of circulating antibodies may limit reactivation of immunological memory and constrain further antibody boosting by mRNA vaccines. These data provide a deeper understanding of how the quantity and quality of antibody and memory B cell responses change over time and number of antigen exposures. These data also provide insight into potential immune dynamics following recall responses to additional vaccine doses or post-vaccination infections.

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“…As of March 30, 2022, the frequency BA.3 remained low in the GISAID database (https://www.gisaid.org/). All three sublineages of Omicron could significantly evade vaccine-elicited neutralization, among which BA.3 exhibited the greatest reduction 3,4 . In addition, Omicron BA.1 could efficiently evade non-Omicron SARS-CoV-2 infection-elicited neutralizationzou 5 .…”

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confidence: 99%

Cross-neutralization of Omicron BA.1 against BA.2 and BA.3 SARS-CoV-2

Zou

Kurhade

Xia

et al. 2022

Preprint

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The Omicron SARS-CoV-2 has three distinct sublineages, among which sublineage BA.1 is responsible for the initial Omicron surge and is now being replaced by BA.2 worldwide, whereas BA.3 is currently at a low frequency. The ongoing BA.1-to-BA.2 replacement underscores the importance to understand the cross-neutralization among the three Omicron sublineages. Here we tested the neutralization of BA.1-infected human sera against BA.2, BA.3, and USA/WA1-2020 (a strain isolated in late January 2020). The BA.1-infected sera neutralized BA.1, BA.2, BA.3, and USA/WA1-2020 SARS-CoV-2s with geometric mean titers (GMTs) of 445, 107, 102, and 16, respectively. Thus, the neutralizing GMTs against heterologous BA.2, BA.3, and USA/WA1-2020 were 4.2-, 4.4-, and 28.4-fold lower than the GMT against homologous BA.1, respectively. These findings have implications for vaccine strategy.

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Neutralization and durability of 2 or 3 doses of the BNT162b2 vaccine against Omicron SARS-CoV-2

Cited by 89 publications

References 15 publications

Neutralization of Omicron BA.1, BA.2, and BA.3 SARS-CoV-2 by 3 doses of BNT162b2 vaccine

Neutralization of Omicron BA.1, BA.2, and BA.3 SARS-CoV-2 by 3 doses of BNT162b2 vaccine

Efficient recall of Omicron-reactive B cell memory after a third dose of SARS-CoV-2 mRNA vaccine

Cross-neutralization of Omicron BA.1 against BA.2 and BA.3 SARS-CoV-2

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