Antibody Response to Omicron BA.4–BA.5 Bivalent Booster

Wang, Qian; Bowen, Anthony; Valdez, Riccardo; Gherasim, Carmen; Gordon, Aubree; Liu, Lihong; Ho, David D.

doi:10.1056/nejmc2213907

Cited by 142 publications

(131 citation statements)

References 4 publications

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“…Covid-19 vaccination policies recommending the bivalent mRNA-booster vaccines as a fourth dose are mainly supported by studies on immunogenicity where some have shown higher induction of antibody levels against omicron subvariants including BA.4-5 compared with monovalent boosters. [4][5][6][7][8] Previous observational effectiveness studies of fourth dose monovalent vaccination, primarily on data from before BA.4-5 subvariant predominance, [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] also lend some indirect support to these recommendations.…”

Section: Discussionmentioning

confidence: 99%

“…While some clinical studies have shown that the bivalent BA.4-5 and BA.1 mRNA-booster vaccines increases neutralizing antibody responses against omicron compared with the original monovalent mRNA Covid-19 vaccines, others have not. [4][5][6][7][8] Data on the comparative effectiveness of the bivalent mRNA-booster vaccines as a fourth dose to protect against severe Covid-19 outcomes are scarce. [9][10][11][12] Previous observational studies of fourth doses are primarily limited to the monovalent mRNA Covid-19 vaccines and mainly during periods prior to the emergence of the current predominating omicron subvariants BA.4 and BA.5.…”

Section: Introductionmentioning

confidence: 99%

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Comparative effectiveness of the bivalent BA.4-5 and BA.1 mRNA-booster vaccines in the Nordic countries

Andersson

Thiesson

Baum

et al. 2023

Preprint

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Background: Data on the comparative vaccine effectiveness (CVE) of the bivalent mRNA-booster vaccines containing the original SARS-CoV-2 and omicron BA.4-5 and BA.1 subvariants are limited. Methods: In a period of BA.4-5 subvariants predominance, we estimated the CVE of the bivalent Comirnaty (Pfizer-BioNTech) and Spikevax (Moderna) BA.4-5 and BA.1 mRNA-booster vaccines given as a fourth dose in Denmark, Finland, Norway, and Sweden. From 1 July 2022 to 12 December 2022, we conducted nationwide cohort analyses using target trial emulation to compare risks of Covid-19 hospitalization and death in four-dose (second booster) with three-dose (first booster) vaccinated and between four-dose vaccinated individuals. Results: Compared with having received three vaccine doses, receipt of a bivalent BA.4-5 booster as a fourth dose was associated with a country-combined CVE against Covid-19 hospitalization of 80.5% (95% confidence interval, 69.5% to 91.5%). The corresponding CVE for bivalent BA.1 boosters was 74.0% (68.6% to 79.4%). CVE against Covid-19 death was 77.8% (48.3% to 100%) and 80.1% (72.0% to 88.2%) for bivalent BA.4-5 and BA.1 boosters as a fourth dose, respectively. The CVE of bivalent BA.4-5 vs. BA.1 boosters were 32.3% (10.6% to 53.9%) for Covid-19 hospitalization and 12.3% (-36.1% to 60.7%) for death (the latter estimable in Denmark only). Conclusions: Vaccination with bivalent BA.4-5 or BA.1 mRNA-booster vaccines as a fourth dose was associated with increased protection against Covid-19 hospitalization and death during a period of BA.4-5 predominance. Bivalent BA.4-5 boosters conferred moderately greater vaccine effectiveness against Covid-19 hospitalization compared with bivalent BA.1 boosters.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Comparative effectiveness of the bivalent BA.4-5 and BA.1 mRNA-booster vaccines in the Nordic countries

Andersson

Thiesson

Baum

et al. 2023

Preprint

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“…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 16,[26][27][28][29] . Most of these studies were performed with lentiviral or VSV pseudotypes.…”

mentioning

confidence: 99%

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

et al. 2023

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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 subvariant BQ.1.1 became predominant in many countries in December 2022. The subvariants 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) lose antiviral efficacy against BA.2.75.2 and BQ.1.1, whereas Xevudy (Sotrovimab) remaine weakly active. BQ.1.1 is also resistant to Bebtelovimab. Neutralizing titers in triply vaccinated individuals are low to undetectable against BQ.1.1 and BA.2.75.2, 4 months after boosting. A BA.1/BA.2 breakthrough infection increases these titers, which remains about 18-fold lower against BA.2.75.2 and BQ.1.1, than against BA.1. Reciprocally, a BA.5 breakthrough infection increases more efficiently neutralization against BA.5 and BQ.1.1 than against BA.2.75.2. Thus, the evolution trajectory of novel Omicron subvariants facilitates their spread in immunized populations and raises concerns about the efficacy of most available mAbs.

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“…S1). The bivalent mRNA vaccine boosters have been shown to increase neutralizing antibody (NAb) titers to multiple variants [1][2][3][4] , but the durability of these responses remains to be determined.…”

mentioning

confidence: 99%

Waning Immunity Against XBB.1.5 Following Bivalent mRNA Boosters

Lasrado

Collier

Miller

et al. 2023

Preprint

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The SARS-CoV-2 Omicron variant has continued to evolve. XBB is a recombinant between two BA.2 sublineages, XBB.1 includes the G252V mutation, and XBB.1.5 includes the G252V and F486P mutations. XBB.1.5 has rapidly increased in frequency and has become the dominant virus in New England. The bivalent mRNA vaccine boosters have been shown to increase neutralizing antibody (NAb) titers to multiple variants, but the durability of these responses remains to be determined. We assessed humoral and cellular immune responses in 30 participants who received the bivalent mRNA boosters and performed assays at baseline prior to boosting, at week 3 after boosting, and at month 3 after boosting. Our data demonstrate that XBB.1.5 substantially escapes NAb responses but not T cell responses after bivalent mRNA boosting. NAb titers to XBB.1 and XBB.1.5 were similar, suggesting that the F486P mutation confers greater transmissibility but not increased immune escape. By month 3, NAb titers to XBB.1 and XBB.1.5 declined essentially to baseline levels prior to boosting, while NAb titers to other variants declined less strikingly.

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Antibody Response to Omicron BA.4–BA.5 Bivalent Booster

Cited by 142 publications

References 4 publications

Comparative effectiveness of the bivalent BA.4-5 and BA.1 mRNA-booster vaccines in the Nordic countries

Comparative effectiveness of the bivalent BA.4-5 and BA.1 mRNA-booster vaccines in the Nordic countries

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

Waning Immunity Against XBB.1.5 Following Bivalent mRNA Boosters

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