Dataset Information

High Individual Heterogeneity of Neutralizing Activities against the Original Strain and Nine Different Variants of SARS-CoV-2.

ABSTRACT: Since the beginning of the COVID-19 pandemic, several SARS-CoV-2 variants have sequentially emerged. In France, most cases were due to spike D641G-harbouring viruses that descended initially from the Wuhan strain, then by the variant of B.1.160 lineage we called Marseille-4 since the summer of 2020, which was followed by the Alpha and Beta variants in early 2021, then the Delta variant currently. We determined the neutralising antibody (nAb) titres in sera from convalescent individuals previously infected by these four major local variants and from vaccine recipients to the original Wuhan strain and nine variants, including two recent circulating Delta isolates. The results show high inter-individual heterogeneity in nAbs, especially according to the variant tested. The major variations among nAbs are based on the genotype responsible for the infection. Patients previously infected with the beta and B.1.160 variants had the lowest nAb titres. We show that this heterogeneity is well explained by spike protein mutants modelling using in silico approaches. The highest titres were observed in individuals vaccinated with the Pfizer/BioNTech COVID-19 vaccine, even against the delta variant. Immunity acquired naturally after infection is highly dependent on the infecting variant, and, unexpectedly, mRNA-based vaccine efficacy was shown to be often better than natural immunity in eliciting neutralising antibodies.

SUBMITTER: Jaafar R

PROVIDER: S-EPMC8623169 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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High Individual Heterogeneity of Neutralizing Activities against the Original Strain and Nine Different Variants of SARS-CoV-2.

Jaafar Rita R Boschi Celine C Aherfi Sarah S Bancod Audrey A Le Bideau Marion M Edouard Sophie S Colson Philippe P Chahinian Henri H Raoult Didier D Yahi Nouara N Fantini Jacques J La Scola Bernard B

Viruses 20211028 11

<h4>Background</h4>Since the beginning of the COVID-19 pandemic, several SARS-CoV-2 variants have sequentially emerged. In France, most cases were due to spike D641G-harbouring viruses that descended initially from the Wuhan strain, then by the variant of B.1.160 lineage we called Marseille-4 since the summer of 2020, which was followed by the Alpha and Beta variants in early 2021, then the Delta variant currently.<h4>Methods</h4>We determined the neutralising antibody (nAb) titres in sera from ...[more]

PMID: 34834983

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Project description:BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) with different resistance levels to existing immunity have recently emerged. Antibodies that recognize the SARS-CoV-2 spike (S) protein and exhibit neutralizing activities are considered the best correlate of protection and an understanding of humoral immunity is crucial for controlling the pandemic. We thus analyzed such antibodies in individuals recovered from infection in 2020 as well as vaccinees after two doses of an mRNA vaccine.MethodsNeutralizing antibody responses against three SARS-CoV-2 variants (D614G, VOCs Beta and Delta) were determined in serum samples from 54 infected individuals (24 non-hospitalized, 30 hospitalized) and 34 vaccinees shortly after symptom onset or second vaccination, respectively, as well as six months later. In addition, the effect of the S sequence of the infecting strain on neutralization was studied.ResultsNon-hospitalized patients had the lowest neutralization titers against all variants, while those of hospitalized patients equaled or exceeded those of vaccinees. Neutralizing activity was lower against the two VOCs and declined significantly in all cohorts after six months. This decrease was more pronounced in hospitalized and vaccinated individuals than in non-hospitalized patients. Of note, the specific neutralizing activity (NT titer/ELISA value ratio) was higher in the infected cohorts than in vaccinees and did not differ between non-hospitalized and hospitalized patients. Patients infected with viral strains carrying mutations in the N-terminal domain of the spike protein were impaired in Beta VOC neutralization.ConclusionsSpecific neutralizing activities were higher in infected than in vaccinated individuals, and no difference in the quality of these antibodies was observed between hospitalized and non-hospitalized patients, despite significantly lower titers in the latter group. Additionally, antibody responses of infected individuals showed greater heterogeneity than those of vaccinees, which was associated with mutations in the spike protein of the infecting strain. Overall, our findings yielded novel insights into SARS-CoV-2-specific neutralizing antibodies, evolving differently after virus infection and COVID-19 vaccination, which is an important issue to consider in ongoing vaccine strategy improvements.

Project description:BackgroundThe ongoing emergence of evolving SARS-CoV-2 variants poses great threaten to the efficacy of authorized monoclonal antibody-based passive immunization or treatments. Developing potent broadly neutralizing antibodies (bNabs) against SARS-CoV-2 and elucidating their potential evolutionary pathways are essential for battling the coronavirus disease 2019 (COVID-19) pandemic.MethodsBroadly neutralizing antibodies were isolated using single cell sorting from three COVID-19 convalescents infected with prototype SARS-CoV-2 strain. Their neutralizing activity against diverse SARS-CoV-2 strains were tested in vitro and in vivo, respectively. The structures of antibody-antigen complexes were resolved using crystallization or Cryo-EM method. Antibodyomics analyses were performed using the non-bias deep sequencing results of BCR repertoires.ResultsWe obtained a series of RBD-specific monoclonal antibodies with highly neutralizing potency against a variety of pseudotyped and live SARS-CoV-2 variants, including five global VOCs and some Omicron subtypes such as BA.1, BA.2, BA.4/5, BF.7, and XBB. 2YYQH9 and LQLD6HL antibody cocktail also displayed good therapeutic and prophylactic efficacy in an XBB.1.16 infected hamster animal model. Cryo-EM and crystal structural analyses revealed that broadly neutralizing antibodies directly blocked the binding of ACE2 by almost covering the entire receptor binding motif (RBM) and largely avoided mutated RBD residues in the VOCs, demonstrating their broad and potent neutralizing activity. In addition, antibodyomics assays indicate that the germline frequencies of RBD-specific antibodies increase after an inactivated vaccine immunization. Moreover, the CDR3 frequencies of Vκ/λ presenting high amino acid identity with the broadly neutralizing antibodies were higher than those of VH.ConclusionsThese data suggest that current identified broadly neutralizing antibodies could serve as promising drug candidates for COVID-19 and can be used for reverse vaccine design against future pandemics.

Dataset Information

High Individual Heterogeneity of Neutralizing Activities against the Original Strain and Nine Different Variants of SARS-CoV-2.

Publications

High Individual Heterogeneity of Neutralizing Activities against the Original Strain and Nine Different Variants of SARS-CoV-2.

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