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

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Abstract

Objectives

Recent 2022 SARS-CoV-2 Omicron variants, have acquired resistance to most neutralizing anti-Spike monoclonal antibodies authorized, and the BQ.1.* sublineages are notably resistant to all authorized monoclonal antibodies. Polyclonal antibodies from individuals both vaccinated and recently recovered from Omicron COVID-19 (VaxCCP) could retain new Omicron neutralizing activity.

Methods

Here we reviewed BQ.1.* virus neutralization data from 920 individual patient samples from 43 separate cohorts defined by boosted vaccinations with or without recent Omicron COVID-19, as well as infection without vaccination.

Results

More than 90% of the plasma samples from individuals in the recently (within 6 months) boosted VaxCCP study cohorts neutralized BQ.1.1, 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 (GM (GMT ₅₀) were 314, 78 and 204 for BQ.1.1, XBB.1 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 GM (GMT ₅₀) for all viral variants.

Conclusions

Boosted 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.1 and BF.7 variants.

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Alarming antibody evasion properties of rising SARS-CoV-2 BQ and XBB subvariants

Qian Wang, Sho Iketani, Zhiteng Li … (2022)

The BQ and XBB subvariants of SARS-CoV-2 Omicron are now rapidly expanding, possibly due to altered antibody evasion properties deriving from their additional spike mutations. Here, we report that neutralization of BQ.1, BQ.1.1, XBB, and XBB.1 by sera from vaccinees and infected persons was markedly impaired, including sera from individuals boosted with a WA1/BA.5 bivalent mRNA vaccine. Titers against BQ and XBB subvariants were lower by 13-81-fold and 66-155-fold, respectively, far beyond what had been observed to date. Monoclonal antibodies capable of neutralizing the original Omicron variant were largely inactive against these new subvariants, and the responsible individual spike mutations were identified. These subvariants were found to have similar ACE2-binding affinities as their predecessors. Together, our findings indicate that BQ and XBB subvariants present serious threats to current COVID-19 vaccines, render inactive all authorized antibodies, and may have gained dominance in the population because of their advantage in evading antibodies. Recent BQ and XBB subvariants of SARS-CoV-2 demonstrate dramatically increased ability to evade neutralizing antibodies, even those from people who received the bivalent mRNA booster or who are immunized and had previous breakthrough Omicron infection. Additionally, both BQ and XBB are completely resistant to bebtelovimab, meaning there are now no clinically authorized therapeutic antibodies effective against these circulating variants.

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Imprinted SARS-CoV-2 humoral immunity induces convergent Omicron RBD evolution

Yunlong Cao, Fanchong Jian, Jing Wang … (2022)

Continuous evolution of Omicron has led to a rapid and simultaneous emergence of numerous variants that display growth advantages over BA.5 (ref. 1 ). Despite their divergent evolutionary courses, mutations on their receptor-binding domain (RBD) converge on several hotspots. The driving force and destination of such sudden convergent evolution and its effect on humoral immunity remain unclear. Here we demonstrate that these convergent mutations can cause evasion of neutralizing antibody drugs and convalescent plasma, including those from BA.5 breakthrough infection, while maintaining sufficient ACE2-binding capability. BQ.1.1.10 (BQ.1.1 + Y144del), BA.4.6.3, XBB and CH.1.1 are the most antibody-evasive strains tested. To delineate the origin of the convergent evolution, we determined the escape mutation profiles and neutralization activity of monoclonal antibodies isolated from individuals who had BA.2 and BA.5 breakthrough infections 2,3 . Owing to humoral immune imprinting, BA.2 and especially BA.5 breakthrough infection reduced the diversity of the neutralizing antibody binding sites and increased proportions of non-neutralizing antibody clones, which, in turn, focused humoral immune pressure and promoted convergent evolution in the RBD. Moreover, we show that the convergent RBD mutations could be accurately inferred by deep mutational scanning profiles 4,5 , and the evolution trends of BA.2.75 and BA.5 subvariants could be well foreseen through constructed convergent pseudovirus mutants. These results suggest that current herd immunity and BA.5 vaccine boosters may not efficiently prevent the infection of Omicron convergent variants.

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Early Outpatient Treatment for Covid-19 with Convalescent Plasma

David Sullivan, Kelly Gebo, Shmuel Shoham … (2022)

Abstract Background Polyclonal convalescent plasma may be obtained from donors who have recovered from coronavirus disease 2019 (Covid-19). The efficacy of this plasma in preventing serious complications in outpatients with recent-onset Covid-19 is uncertain. Methods In this multicenter, double-blind, randomized, controlled trial, we evaluated the efficacy and safety of Covid-19 convalescent plasma, as compared with control plasma, in symptomatic adults (≥18 years of age) who had tested positive for severe acute respiratory syndrome coronavirus 2, regardless of their risk factors for disease progression or vaccination status. Participants were enrolled within 8 days after symptom onset and received a transfusion within 1 day after randomization. The primary outcome was Covid-19–related hospitalization within 28 days after transfusion. Results Participants were enrolled from June 3, 2020, through October 1, 2021. A total of 1225 participants underwent randomization, and 1181 received a transfusion. In the prespecified modified intention-to-treat analysis that included only participants who received a transfusion, the primary outcome occurred in 17 of 592 participants (2.9%) who received convalescent plasma and 37 of 589 participants (6.3%) who received control plasma (absolute risk reduction, 3.4 percentage points; 95% confidence interval, 1.0 to 5.8; P=0.005), which corresponded to a relative risk reduction of 54%. Evidence of efficacy in vaccinated participants cannot be inferred from these data because 53 of the 54 participants with Covid-19 who were hospitalized were unvaccinated and 1 participant was partially vaccinated. A total of 16 grade 3 or 4 adverse events (7 in the convalescent-plasma group and 9 in the control-plasma group) occurred in participants who were not hospitalized. Conclusions In participants with Covid-19, most of whom were unvaccinated, the administration of convalescent plasma within 9 days after the onset of symptoms reduced the risk of disease progression leading to hospitalization. (Funded by the Department of Defense and others; CSSC-004 ClinicalTrials.gov number, NCT04373460.)

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Author and article information

Journal

Journal ID (nlm-ta): bioRxiv

Journal ID (publisher-id): BIORXIV

Title: bioRxiv

Publisher: Cold Spring Harbor Laboratory

Publication date (Electronic): 16 December 2022

Electronic Location Identifier: 2022.11.25.517977

Affiliations

[1 ]Johns Hopkins Bloomberg School of Public Health and School of Medicine, Baltimore, MD 21218, USA

[2 ]Division of Transfusion Medicine, Carlo Poma Hospital, 46100 Mantua, Italy

[3 ]Department of Anesthesiology & Perioperative Medicine, Mayo Clinic, Rochester, MN 55902, USA

[4 ]North-Western Tuscany Blood Bank, Pisa University Hospital, 56124 Pisa, Italy

Author notes

Author contributions:

DJS: data extraction, table curation and design, and writing original draft; D.F.: conceptualization, data access and verification and manuscript revision; M.F. data access and verification and manuscript revision; JWS data access and verification and manuscript revision, MJJ and AC manuscript revision.

Corresponding author: David Sullivan, 615 N. Wolfe St Rm W4606, Baltimore MD 21205. Tel 410 502 2522, fax 410 955 0105. dsulliv7@ 123456jhmi.edu

Article

DOI: 10.1101/2022.11.25.517977

PMC ID: 9727765

PubMed ID: 36482971

SO-VID: 4c68b0fe-493a-48fa-99a4-6f5681872a15

License:

This work is licensed under a Creative Commons Attribution-NoDerivatives 4.0 International License, which allows reusers to copy and distribute the material in any medium or format in unadapted form only, and only so long as attribution is given to the creator. The license allows for commercial use.

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

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Abstract

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Novel Coronavirus Disease COVID-19

Most cited references 20

Alarming antibody evasion properties of rising SARS-CoV-2 BQ and XBB subvariants

Imprinted SARS-CoV-2 humoral immunity induces convergent Omicron RBD evolution

Early Outpatient Treatment for Covid-19 with Convalescent Plasma

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