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

Zou, Jing; Kurhade, Chaitanya; Patel, Sohil; Kitchin, Nicholas; Tompkins, Kristin; Cutler, Mark; Cooper, David A.; Yang, Qi; Cai, Hui; Muik, Alexander; Zhang, Ying; Lee, Dung-Yang; Şahin, Uğur; Anderson, Annaliesa S.; Gruber, William C.; Xie, Xuping; Swanson, Kena A.; Shi, Pei–Yong

doi:10.1056/nejmc2214916

Cited by 139 publications

(122 citation statements)

References 6 publications

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“…Although vaccines effectively reduce this burden, immunity wanes in the months following vaccination (2,3) and the virus continues to evolve to escape population immunity (4,5). As newer versions of vaccines are adapted to recent SARS-CoV-2 variants (i.e., bivalent vaccine) (6), we must continue to determine how effective these vaccines are over time and against emerging variants and especially in vulnerable populations.…”

Section: Introductionmentioning

confidence: 99%

Durability of immunity and clinical protection in nursing home residents following bivalent SARS-CoV-2 vaccination

Gravenstein

DeVone

Oyebanji

et al. 2023

Preprint

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Background: Vaccines have substantially mitigated the disproportional impact of SARS-CoV-2 on the high morbidity and mortality experienced by nursing home residents. However, variation in vaccine efficacy, immune senescence and waning immunity all undermine vaccine effectiveness over time. The introduction of the bivalent vaccine in September 2022 aimed to counter this increasing susceptibility and consequences of breakthrough infection, however data on the durability and protection of the vaccine are limited. We evaluated the durability of immunity and protection after the first bivalent vaccination to SARS-CoV-2 in nursing home residents. Methods: For the immunologic evaluation, community nursing home volunteers agreed to serial blood sampling before, at two weeks, three and six months after each vaccination for antibodies to spike protein and pseudovirus neutralization activity over time. Concurrent clinical outcomes were evaluated by reviewing electronic health record data from residents living in Veterans Administration managed nursing home units. Residents without recent infection but prior vaccination to SARS-CoV-2 were followed over time beginning with administration of the newly available bivalent vaccine using a target trial emulation (TTE) approach; TTE compared time to breakthrough infection, hospitalization and death between those who did and did not receive the bivalent vaccine. Results: We evaluated antibodies in 650 nursing home residents; 452 had data available following a first monovalent booster, 257 following a second monovalent booster and 321 following a bivalent vaccine. We found a rise in BA.5 neutralization activity from the first and second monovalent boosters through the bivalent vaccination regardless of prior SARS-CoV-2 history. Titers declined at three and six months after the bivalent vaccination but generally exceeded those at three months compared to either prior boost. BA.5 neutralization titers six months after the bivalent vaccination were diminished but had detectable levels in 80% of infection-naive and 100% of prior infected individuals. TTE evaluated 5903 unique subjects, of whom 2235 received the bivalent boost. TTE demonstrated 39% or greater reduction in risk of infection, hospitalization or death at four months following the bivalent boost. Conclusion: Immunologic results mirrored those of the TTE and suggest bivalent vaccination added substantial protection for up to six months after bivalent vaccination with notable exceptions. However, the level of protection declined over this period, and by six months may open a window of added vulnerability to infection before the next updated vaccine becomes available. We strongly agree with the CDC recommendation that those who have not received a bivalent vaccination receive that now and these results support a second bivalent booster for those at greatest risk which includes many nursing home residents.

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Section: Introductionmentioning

confidence: 99%

Durability of immunity and clinical protection in nursing home residents following bivalent SARS-CoV-2 vaccination

Gravenstein

DeVone

Oyebanji

et al. 2023

Preprint

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“…The SARS-CoV-2 XBB lineage possesses an extraordinarily high capacity for antibody evasion due to its unique set of S protein mutations [1][2][3][4]. However, this trait may have come at the cost of a moderately reduced host cell entry efficiency as suggested by recent in vitro data [1,5], which may explain why infections caused by XBB sublineages only accounted for a small proportion of total SARS-CoV-2 infections in several countries (except India) so far (Fig.…”

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confidence: 99%

Profound neutralization evasion and augmented host cell entry are hallmarks of the fast-spreading SARS-CoV-2 lineage XBB.1.5

et al. 2023

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“…Along with dramatic changes in S-protein, the miRNA-driven alterations of NSP4, acquired during prolonged replication with the intestine, may have contributed to the current global dominance of the descendants of the BA.2 variant [54]. Our findings highlight the possibility that intestinal tissue may significantly impact evolution of the SARS-CoV-2 genome and may play a pivotal role in the long COVID.…”

Section: Discussionmentioning

confidence: 77%

miRNA binding pressure channels evolution of SARS-CoV-2 genomes

Zhiyanov

Shkurnikov

Nersisyan

et al. 2023

Preprint

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In somatic cells, microRNAs (miRNAs) bind to the genomes of RNA viruses and influence their translation and replication. Here we demonstrate that a significant number of miRNA binding sites locate in the NSP4 region of the SARS-CoV-2 genome, and the intestinal human miRNAs exert evolutionary pressure on this region. Notably, in infected cells, NSP4 promotes the formation of double-membrane vesicles, which serve as the scaffolds for replication-transcriptional complexes and protect viral RNA from intracellular destruction. In three years of selection, the loss of many miRNA binding sites, in particular, those within the NSP4, has shaped the SARS-CoV-2 genomes to promote the descendants of the BA.2 variants as the dominant strains and define current momentum of the pandemics.

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

Cited by 139 publications

References 6 publications

Durability of immunity and clinical protection in nursing home residents following bivalent SARS-CoV-2 vaccination

Durability of immunity and clinical protection in nursing home residents following bivalent SARS-CoV-2 vaccination

Profound neutralization evasion and augmented host cell entry are hallmarks of the fast-spreading SARS-CoV-2 lineage XBB.1.5

miRNA binding pressure channels evolution of SARS-CoV-2 genomes

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