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SARS-CoV-2 Omicron variant escapes neutralizing antibodies and T cell responses more efficiently than other variants in mild COVID-19 convalescents.

ABSTRACT: Coronavirus disease 2019 (COVID-19) convalescents living in regions with low vaccination rates rely on post-infection immunity for protection against re-infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We evaluate humoral and T cell immunity against five variants of concern (VOCs) in mild-COVID-19 convalescents at 12 months after infection with ancestral virus. In this cohort, ancestral, receptor-binding domain (RBD)-specific antibody and circulating memory B cell levels are conserved in most individuals, and yet serum neutralization against live B.1.1.529 (Omicron) is completely abrogated and significantly reduced for other VOCs. Likewise, ancestral SARS-CoV-2-specific memory T cell frequencies are maintained in >50% of convalescents, but the cytokine response in these cells to mutated spike epitopes corresponding to B.1.1.529 and B.1.351 (Beta) VOCs were impaired. These results indicate that increased antigen variability in VOCs impairs humoral and spike-specific T cell immunity post-infection, strongly suggesting that COVID-19 convalescents are vulnerable and at risk of re-infection with VOCs, thus stressing the importance of vaccination programs.

SUBMITTER: Garcia-Valtanen P

PROVIDER: S-EPMC9110310 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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SARS-CoV-2 Omicron variant escapes neutralizing antibodies and T cell responses more efficiently than other variants in mild COVID-19 convalescents.

Garcia-Valtanen Pablo P Hope Christopher M CM Masavuli Makutiro G MG Yeow Arthur Eng Lip AEL Balachandran Harikrishnan H Mekonnen Zelalem A ZA Al-Delfi Zahraa Z Abayasingam Arunasingam A Agapiou David D Stella Alberto Ospina AO Aggarwal Anupriya A Bouras George G Gummow Jason J Ferguson Catherine C O'Connor Stephanie S McCartney Erin M EM Lynn David J DJ Maddern Guy G Gowans Eric J EJ Reddi Benjamin A J BAJ Shaw David D Kok-Lim Chuan C Beard Michael R MR Weiskopf Daniela D Sette Alessandro A Turville Stuart G SG Bull Rowena A RA Barry Simon C SC Grubor-Bauk Branka B

Cell reports. Medicine 20220517 6

Coronavirus disease 2019 (COVID-19) convalescents living in regions with low vaccination rates rely on post-infection immunity for protection against re-infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We evaluate humoral and T cell immunity against five variants of concern (VOCs) in mild-COVID-19 convalescents at 12 months after infection with ancestral virus. In this cohort, ancestral, receptor-binding domain (RBD)-specific antibody and circulating memory B cell lev ...[more]

PMID: 35654046

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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

SARS-CoV-2 Omicron variant escapes neutralizing antibodies and T cell responses more efficiently than other variants in mild COVID-19 convalescents.

Publications

SARS-CoV-2 Omicron variant escapes neutralizing antibodies and T cell responses more efficiently than other variants in mild COVID-19 convalescents.

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