Analysis of anti-SARS-CoV-2 Omicron-neutralizing antibody titers in different vaccinated and unvaccinated convalescent plasma sources

Sullivan, David J.; Franchini, Massimo; Joyner, Michael J.; Casadevall, Arturo; Focosi, Daniele

doi:10.1038/s41467-022-33864-y

Cited by 73 publications

(58 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this setting, polyclonal passive immunotherapies (such as plasma from convalescent and vaccinated donors [60,61]) appear more escape-resistant than monoclonal antibodies [62][63][64][65], and combo therapies should be urgently investigated and deployed in vulnerable populations, such as IC patients [66].…”

Section: Discussionmentioning

confidence: 99%

Convergent evolution in SARS-CoV-2 Spike creates a variant soup that causes new COVID-19 waves

Focosi¹,

Quiroga

McConnell

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

The first 2 years of the COVID-19 pandemic were mainly characterized by convergent evolution of mutations of SARS-CoV-2 Spike protein at residues K417, L452, E484, N501 and P681 across different variants of concern (Alpha, Beta, Gamma, and Delta). Since Spring 2022 and the third year of the pandemic, with the advent of Omicron and its sublineages, convergent evolution has led to the observation of different lineages acquiring an additional group of mutations at different amino acid residues, namely R346, K444, N450, N460, F486, F490, Q493, and S494. Mutations at these residues have become increasingly prevalent during Summer and Autumn 2022, with combinations showing increased fitness. The most likely reason for this convergence is the selective pressure exerted by previous infection- or vaccine-elicited immunity. Such accelerated evolution has caused failure of all anti-Spike monoclonal antibodies, including bebtelovimab and cilgavimab. While we are learning how fast coronaviruses can mutate and recombine, we should reconsider opportunities for economically sustainable escape-proof combination therapies, and reevaluate the potential for polyclonal therapies (such as COVID19 convalescent plasma) in immunocompromised patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Convergent evolution in SARS-CoV-2 Spike creates a variant soup that causes new COVID-19 waves

Focosi¹,

Quiroga

McConnell

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…* and BF.7 sublineages are also highly resistant to anti-Spike mAbs (3). Polyclonal plasma from individuals who are both vaccinated and had COVID-19 (VaxCCP) has more than ten times the antibody levels capable of neutralizing pre-Omicron variants as well as Omicron variants BA.1 through BA.4/5 (4,5). Polyclonal COVID-19 convalescent plasma (CCP) has thousands of distinct antibody specificities of different isotypes, including many capable of SARS-CoV-2 neutralization.…”

Section: Introductionmentioning

confidence: 99%

“…Polyclonal COVID-19 convalescent plasma (CCP) has thousands of distinct antibody specificities of different isotypes, including many capable of SARS-CoV-2 neutralization. High-titer pre-Omicron CCP contains Omicron neutralizing activity despite being collected before variant appearance (4,5). Given that CCP remains a recommended therapy for IC (1,6,7), we systematically reviewed recent primary research for neutralization results against BQ.1.1 by plasma collected from vaccinated subjects with or without COVID-19 or after recent Omicron infection alone.…”

Section: Introductionmentioning

confidence: 99%

“…* defeating the remaining anti-Spike mAbs, boosted VaxCCP, recently collected within the last 6 months of either a vaccine dose or SARS-CoV-2 is likely to be the only viable remaining passive antibody therapy in the 2022-23 Winter for IC patients who have failed to make antibodies after vaccination and still require B-cell depleting drugs or immunosuppressive therapy. In a literature review of CCP from diverse VOC waves as well as boosted vaccinees and VaxCCP up to BA-1, VaxCCP showed higher neutralization titers against Omicron at levels above 300 dilutional GMT50 4 . The accelerated evolution of SARS-CoV-2 VOCs has created the problem that the pharmaceutical development of additional mAbs is not worth the effort and cost given their expected short useful clinical life expectancy, so the anti-Spike mAb pipeline has remained stuck in 2022.…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

Self Cite

View full text Add to dashboard Cite

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.

show abstract

COVID-19 Convalescent Plasma for the Treatment of Immunocompromised Patients: A Systematic Review and Meta-analysis

et al. 2023

Self Cite

View full text Add to dashboard Cite

ImportancePatients who are immunocompromised have increased risk for morbidity and mortality associated with coronavirus disease 2019 (COVID-19) because they less frequently mount antibody responses to vaccines. Although neutralizing anti-spike monoclonal-antibody treatment has been widely used to treat COVID-19, evolutions of SARS-CoV-2 have been associated with monoclonal antibody-resistant SARS-CoV-2 variants and greater virulence and transmissibility of SARS-CoV-2. Thus, the therapeutic use of COVID-19 convalescent plasma has increased on the presumption that such plasma contains potentially therapeutic antibodies to SARS-CoV-2 that can be passively transferred to the plasma recipient.ObjectiveTo assess the growing number of reports of clinical experiences of patients with COVID-19 who are immunocompromised and treated with specific neutralizing antibodies via COVID-19 convalescent plasma transfusion.Data SourcesOn August 12, 2022, a systematic search was performed for clinical studies of COVID-19 convalescent plasma use in patients who are immunocompromised.Study SelectionRandomized clinical trials, matched cohort studies, and case report or series on COVID-19 convalescent plasma use in patients who are immunocompromised were included. The electronic search yielded 462 unique records, of which 199 were considered for full-text screening.Data Extraction and SynthesisThe study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data were extracted by 3 independent reviewers in duplicate and pooled.Main Outcomes and MeauresThe prespecified end point was all-cause mortality after COVID-19 convalescent plasma transfusion; exploratory subgroup analyses were performed based on putative factors associated with the potential mortality benefit of convalescent plasma.ResultsThis systematic review and meta-analysis included 3 randomized clinical trials enrolling 1487 participants and 5 controlled studies. Additionally, 125 case series or reports enrolling 265 participants and 13 uncontrolled large case series enrolling 358 participants were included. Separate meta-analyses, using models both stratified and pooled by study type (ie, randomized clinical trials and matched cohort studies), demonstrated that transfusion of COVID-19 convalescent plasma was associated with a decrease in mortality compared with the control cohort for the amalgam of both randomized clinical trials and matched cohort studies (risk ratio [RR], 0.63 [95% CI, 0.50-0.79]).Conclusions and RelevanceThese findings suggest that transfusion of COVID-19 convalescent plasma is associated with mortality benefit for patients who are immunocompromised and have COVID-19.

show abstract

Analysis of anti-SARS-CoV-2 Omicron-neutralizing antibody titers in different vaccinated and unvaccinated convalescent plasma sources

Cited by 73 publications

References 53 publications

Convergent evolution in SARS-CoV-2 Spike creates a variant soup that causes new COVID-19 waves

Convergent evolution in SARS-CoV-2 Spike creates a variant soup that causes new COVID-19 waves

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

COVID-19 Convalescent Plasma for the Treatment of Immunocompromised Patients: A Systematic Review and Meta-analysis

Contact Info

Product

Resources

About