mRNA bivalent booster enhances neutralization against BA.2.75.2 and BQ.1.1

Davis-Gardner, Meredith E.; Lai, Lilin; Wali, Bushra; Samaha, Hady; Solis, D.; Lee, Matthew; Porter-Morrison, Andrea; Hentenaar, Ian; Yamamoto, Fumiko; Godbole, Sucheta; Douek, Daniel C.; Lee, Frances Eun-Hyung; Rouphael, Nadine; Moreno, Alberto; Pinsky, Benjamin A.; Suthar, Mehul S.

doi:10.1101/2022.10.31.514636

Cited by 30 publications

(35 citation statements)

References 6 publications

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“…Preliminary preprints using lentiviral pseudotypes indicated that BA.5, BA.4.6 or BA.2.75 titers were comparable after monovalent or BA.5 bivalent boosters 25,27 . In contrast, when using tests based on recombinant SARS-CoV-2 infectious virus carrying spikes from different Omicron sublineages, it was observed that bivalent mRNA booster may broaden humoral immunity 26 . These discrepancies may be due to differences in experimental systems, the delay between booster administration and blood sampling and/or variation in immune imprinting across cohorts.…”

Section: Discussionmentioning

confidence: 94%

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Resistance of Omicron subvariants BA.2.75.2, BA.4.6 and BQ.1.1 to neutralizing antibodies

Planas

Bruel

Staropoli

et al. 2022

Preprint

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Convergent evolution of SARS-CoV-2 Omicron BA.2, BA.4 and BA.5 lineages has led to the emergence of several new subvariants, including BA.2.75.2, BA.4.6. and BQ.1.1. The subvariants BA.2.75.2 and BQ.1.1 are expected to become predominant in many countries in November 2022. They carry an additional and often redundant set of mutations in the spike, likely responsible for increased transmissibility and immune evasion. Here, we established a viral amplification procedure to easily isolate Omicron strains. We examined their sensitivity to 6 therapeutic monoclonal antibodies (mAbs) and to 72 sera from Pfizer BNT162b2-vaccinated individuals, with or without BA.1/BA.2 or BA.5 breakthrough infection. Ronapreve (Casirivimab and Imdevimab) and Evusheld (Cilgavimab and Tixagevimab) lost any antiviral efficacy against BA.2.75.2 and BQ.1.1, whereas Xevudy (Sotrovimab) remained weakly active. BQ.1.1 was also resistant to Bebtelovimab. Neutralizing titers in triply vaccinated individuals were low to undetectable against BQ.1.1 and BA.2.75.2, 4 months after boosting. A BA.1/BA.2 breakthrough infection increased these titers, which remained about 18-fold lower against BA.2.75.2 and BQ.1.1, than against BA.1. Reciprocally, a BA.5 breakthrough infection increased more efficiently neutralization against BA.5 and BQ.1.1 than against BA.2.75.2. Thus, the evolution trajectory of novel Omicron subvariants facilitated their spread in immunized populations and raises concerns about the efficacy of most currently available mAbs.

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Section: Discussionmentioning

confidence: 94%

“…A few recent articles and preprints reported an extensive escape of these Omicron subvariants to neutralization, studying sera from individuals who received three or four vaccine doses, including a bivalent booster 25 26 17,27 . Most of these studies were performed with lentiviral or VSV pseudotypes.…”

Section: Introductionmentioning

confidence: 99%

Resistance of Omicron subvariants BA.2.75.2, BA.4.6 and BQ.1.1 to neutralizing antibodies

Planas

Bruel

Staropoli

et al. 2022

Preprint

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“…Among Omicron variants, the association was strongly attenuated ( Figure 5 ), consistent with Omicron’s resistance to vaccine-elicited neutralizing antibodies, which are a key aspect of protection from infection. 7,8,11 The ability of bivalent vaccines to offer additional protection against Omicron-related infections is still being resolved, 29,30 and the neutralizing antibody sensitivity of emergent variants may impact the ability of vaccine boosters to slow transition times to new variants going forward.…”

Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 variant transition dynamics are associated with vaccination rates, number of co-circulating variants, and natural immunity

Beesley

Moran

Wagh

et al. 2022

Preprint

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Background: Throughout the COVID-19 pandemic, the SARS-CoV-2 virus has continued to evolve, with new variants outcompeting existing variants and often leading to different dynamics of disease spread. Methods: In this paper, we performed a retrospective analysis using longitudinal sequencing data to characterize differences in the speed, calendar timing, and magnitude of 13 SARS-CoV-2 variant waves/transitions for 215 countries and sub-country regions, between October 2020 and October 2022. We then clustered geographic locations in terms of their variant behavior across all Omicron variants, allowing us to identify groups of locations exhibiting similar variant transitions. Finally, we explored relationships between heterogeneity in these variant waves and time-varying factors, including vaccination status of the population, governmental policy, and the number of variants in simultaneous competition. Findings: This work demonstrates associations between the behavior of an emerging variant and the number of co-circulating variants as well as the demographic context of the population. We also observed an association between high vaccination rates and variant transition dynamics prior to the Mu and Delta variant transitions. Interpretation: These results suggest the behavior of an emergent variant may be sensitive to the immunologic and demographic context of its location. Additionally, this work represents the most comprehensive characterization of variant transitions globally to date. Funding: Laboratory Directed Research and Development (LDRD), Los Alamos National Laboratory

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“…Currently, new Omicron BA.2- and BA.4/BA.5-descendent sublineages (e.g., BA.4.6, BA.2.75.2, BQ.1.1, and XBB.1) have emerged (https://covid.cdc.gov/covid-data-tracker/#variant-proportions). Although early epidemiological data suggest these new sublineages have not shown signs of increased disease severity, they have accumulated additional spike mutations that could further evade vaccine- and/or infection-elicited antibody neutralization 2–4 . Here we compared the neutralization activities against these Omicron sublineages after a 4 th dose (following three doses of BNT162b2) of either the original monovalent BNT162b2 or the bivalent BA.4/5 booster in humans.…”

Section: Main Textmentioning

confidence: 99%

“…Although early epidemiological data suggest these new sublineages have not shown signs of increased disease severity, they have accumulated additional spike mutations that could further evade vaccine-and/or infection-elicited antibody neutralization [2][3][4] . Here we compared the neutralization activities against these Omicron sublineages after a 4 th dose (following three doses of BNT162b2) of either the original monovalent BNT162b2 or the bivalent BA.…”

mentioning

confidence: 99%

Improved Neutralization of Omicron BA.4/5, BA.4.6, BA.2.75.2, BQ.1.1, and XBB.1 with Bivalent BA.4/5 Vaccine

Zou

Kurhade

Patel

et al. 2022

Preprint

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The BNT162b2 bivalent BA.4/5 COVID-19 vaccine has been authorized to mitigate COVID-19 due to current Omicron and potentially future variants. New sublineages of SARS-CoV-2 Omicron continue to emerge and have acquired additional mutations, particularly in the spike protein, that may lead to improved viral fitness and immune evasion. The present study characterized neutralization activities against new Omicron sublineages BA.4.6, BA.2.75.2, BQ.1.1, and XBB.1 after a 4th dose (following three doses of BNT162b2) of either the original monovalent BNT162b2 or the bivalent BA.4/5 booster in individuals >55 years of age. For all participants, the 4th dose of monovalent BNT162b2 vaccine induced a 3.0, 2.9, 2.3, 2.1, 1.8, and 1.5 geometric mean neutralizing titer fold rise (GMFR) against USA/WA1-2020 (a strain isolated in January 2020), BA.4/5, BA.4.6, BA.2.75.2, BQ.1.1, and XBB.1, respectively; the bivalent vaccine induced 5.8, 13.0, 11.1, 6.7, 8.7, and 4.8 GMFRs. For individuals without SARS-CoV-2 infection history, BNT162b2 monovalent induced 4.4, 3.0, 2.5, 2.0, 1.5, and 1.3 GMFRs, respectively; the bivalent vaccine induced 9.9, 26.4, 22.2, 8.4, 12.6, and 4.7 GMFRs. These data suggest the bivalent BA.4/5 vaccine is more immunogenic than the original BNT162b2 monovalent vaccine against circulating Omicron sublineages, including BQ.1.1 that is becoming prevalent globally.

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mRNA bivalent booster enhances neutralization against BA.2.75.2 and BQ.1.1

Cited by 30 publications

References 6 publications

Resistance of Omicron subvariants BA.2.75.2, BA.4.6 and BQ.1.1 to neutralizing antibodies

Resistance of Omicron subvariants BA.2.75.2, BA.4.6 and BQ.1.1 to neutralizing antibodies

SARS-CoV-2 variant transition dynamics are associated with vaccination rates, number of co-circulating variants, and natural immunity

Improved Neutralization of Omicron BA.4/5, BA.4.6, BA.2.75.2, BQ.1.1, and XBB.1 with Bivalent BA.4/5 Vaccine

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