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, 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:10.1101/2022.11.17.516898

Cited by 44 publications

(41 citation statements)

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“…Zou et al . in the USA in the Summer and Fall of 2022 sampled individuals who had already received 3 mRNA BNT162b2 vaccinations with or without previous COVID-19, both before and about 4 weeks after a 4 th monovalent or bivalent vaccine booster vaccination(9). Miller et al .…”

Section: Resultsmentioning

confidence: 99%

“…Notably, Planas et al employed the IGROV-1 cell type for better growth of Omicron sublineages(11). While the single study fold reductions (FR) and percent neutralizations normalize the results between studies, the GMT 50 can vary between studies even amongst the live authentic viral neutralization studies (e.g., mNeonGreen™ reporter assays versus cytopathic effects)(9, 13). We sorted the live authentic viral neutralizations from the pseudoviral neutralizations, plotting also the minimum and maximums ( Supplementary Figures 1-3 ).…”

Section: Resultsmentioning

confidence: 99%

“…In those vaccinated with last dose more than 6 months prior to sample collection, both the neutralization percent and neutralizing antibody titers fell further, compared to the recently boosted VaxCCP group. Four studies (Planas(11), Zou(9), Cao(3) and Kurhade(13)) had directly comparative cohorts in the three groups which increases the robustness reduction in neutralizations with the vaccine only or more than 6 months to last vaccine or infection event compared to VaxCCP. The main limitation of our systematic review is the small number of studies reporting virus neutralization with BQ.1.1 with most available as pre-preprints without peer-review yet.…”

Section: Discussionmentioning

confidence: 99%

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Plasma after both SARS-CoV-2 boosted vaccination and COVID-19 potently neutralizes BQ.1.1 and XBB.1

Sullivan

Franchini

Senefeld

et al. 2022

Preprint

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BackgroundThe SARS-CoV-2 Omicron variants, dominating in the late 2022 COVID-19 waves, have acquired resistance to most neutralizing anti-Spike monoclonal antibodies authorized so far, and the BQ.1.* sublineages, dominant in the western countries, are notably resistant to all authorized monoclonal antibodies. Polyclonal antibodies from individuals both with at least 3 vaccine doses and also recently recovered from Omicron COVID-19 (VaxCCP) could retain neutralizing activity against such new Omicron lineages.MethodsHere we reviewed BQ.1.1 virus neutralization data from 652 individual patient samples from 32 separate cohorts defined by boosted vaccinations with or without recent Omicron COVID-19, as well as infection without vaccination.FindingsMore than 97% of the plasma samples from individuals in the recently (within 6 months) boosted VaxCCP study cohorts neutralized BQ.1.1, XBB and BF.7 with 100% neutralization of WA-1, BA.4/5, BA.4.6 and BA.2.75. The geometric mean of the geometric mean 50% neutralizing titers (GMT(GMT50) were 201, 52 and 204 for BQ.1.1, XBB and BF.7, respectively. Compared to VaxCCP, plasma sampled from COVID-19 naïve subjects who also recently within 6 months received at least a third vaccine dose had about half of the GMT(GMT50) for all viral variants with percent neutralizations of 82%, 60% and 94% for BQ.1.1, XBB and BF.7, respectively.InterpretationBoosted VaxCCP characterized by either recent vaccine dose or infection event within 6 months represents a robust, variant-resilient, passive immunotherapy against the new Omicron BQ.1.1, XBB and BF.7 variants.FundingDepartment of Defense in collaboration with the Defense Health Agency, National Institute of Allergy and Infectious Diseases, National Institutes of Health.Research in ContextEvidence before this studyPassive antibody therapy is necessary for both prophylaxis and therapy of immunocompromised COVID-19 patients. The currently dominant SARS-CoV-2 Omicron BQ.1.1 variant is now resistantin vitroto all clinically authorized monoclonal antibodies making COVID-19 convalescent plasma the only remaining option for passive immunotherapy in the immunocompromised. There is scattered data about the efficacy of convalescent plasma at neutralizing BQ.1.1. The few prepublished manuscripts individually have limited numbers (less than 100) in subject cohorts, making systematic reviews necessary to draw robust conclusions. We searched PubMed, medRxiv and bioRxiv for manuscripts reporting virus neutralizations for BQ.1.1 using English language as a restriction. Articles lacking plasma BQ.1.1 virus neutralizations were excluded.Added value of this studyPlasma collected from donors both recently (within 6 months) vaccine boosted and convalescent from COVID-19 (VaxCCP) neutralizes BQ.1.1, XBB and BF.7 in more than 95% of cases, and with high neutralizing titers.Implications of all the available evidenceBoosted VaxCCP remains active against BQ.1.1 and other recent Omicron variants dominating the 2022-2023 Winter wave and represents a robust COVID-19 passive immunotherapy for immunocompromised patients.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Plasma after both SARS-CoV-2 boosted vaccination and COVID-19 potently neutralizes BQ.1.1 and XBB.1

Sullivan

Franchini

Senefeld

et al. 2022

Preprint

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“…When we experienced the Omicron wave from late 2021 to early 2022, the BNT162b2 vaccine showed reduced effectiveness in preventing symptomatic SARS-CoV-2 infection compared to during the Delta wave period [ 17 ], with recommendations for a booster vaccination to be given to prevent Omicron-related hospitalization/illness [ 18 , 19 ]. With the advent of newer variants (e.g., BA.4, BA.5, XBB) with enhanced immune evasion [ 20 , 21 ], VE against hospitalization was further compromised [ 22 ], with calls for additional doses of bivalent vaccine to improve protection [ 23 , 24 ]. Furthermore, the definition of VE has varied from study to study.…”

Section: Environmental Factors That Can Impact Vementioning

confidence: 99%

Considerations in Understanding Vaccine Effectiveness

Lau

2022

Vaccines

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Although vaccine effectiveness reports are essential to assessing policies on SARS-CoV-2 vaccination, several factors can affect our interpretation of the results. These include the waning of antibodies, the prevailing viral variants at the time of the study, and COVID-19 disease prevalence in the population. Disease prevalence significantly impacts absolute risk reduction and could skew expected efficacy when increased disease prevalence inflates the absolute risk reduction in the face of a constant relative risk reduction. These factors must be considered in the interpretation of vaccine effectiveness to better understand how vaccines can improve disease prevention among the population. We highlight the impact of various factors on vaccine effectiveness.

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“…Another bivalent vaccine comprising Omicron BA.2 and Delta bivalent LNP-mRNA demonstrated a robust antibody response not only for BA.2 but also for BA.2.12.1, BA.2.75, and BA.5 Omicron subvariants. Similarly, the BNT162b2 bivalent BA.4/5 COVID-19 vaccine also showed higher neutralization titers against BA.4.6, BA.2.75.2, BQ.1.1, and XBB.1 subvariant when tested in participants aged >55 years [ 11 ]. These data cumulatively support the decision to use these bivalent vaccines for their second booster [ 12 ].…”

mentioning

confidence: 99%