A single dose of the SARS-CoV-2 vaccine BNT162b2 elicits Fc-mediated antibody effector functions and T cell responses

Tauzin, Alexandra; Nayrac, Manon; Benlarbi, Mehdi; Gong, Shang Yu; Gasser, Romain; Beaudoin-Bussières, Guillaume; Brassard, Nathalie; Laumaea, Annemarie; Vézina, Dani; Prévost, Jérémie; Anand, Sai Priya; Bourassa, Catherine; Gendron‐Lepage, Gabrielle; Medjahed, Halima; Goyette, Guillaume; Nießl, Julia; Tastet, Olivier; Gokool, Laurie; Morrisseau, Chantal; Arlotto, Pascale; Stamatatos, Leonidas; McGuire, Andrew T.; Larochelle, Catherine; Uchil, Pradeep D.; Lu, Maolin; Mothes, Walther; Serres, Gaston De; Moreira, Sandrine; Roger, Michel; Richard, Jonathan; Martel-Laferrière, Valérie; Duerr, Ralf; Tremblay, Cécile; Kaufmann, Daniel E.; Finzi, Andrés

doi:10.1016/j.chom.2021.06.001

Cited by 187 publications

(169 citation statements)

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“…It is now well established that SARS-CoV-2-specific antibodies can drive varied antiviral functions beyond neutralization 34,43,52 . These responses have been less well characterized, but accumulating evidence suggests their importance to protection from infection and disease.…”

Section: Discussionmentioning

confidence: 99%

Antibody Attributes that Predict the Neutralization and Effector Function of Polyclonal Responses to SARS-CoV-2

Natarajan

Crowley

et al. 2021

Preprint

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While antibodies provide significant protection from SARS-CoV-2 infection and disease sequelae, the specific attributes of the humoral response that contribute to immunity are incompletely defined. In this study, we employ machine learning to relate characteristics of the polyclonal antibody response raised by natural infection to diverse antibody effector functions and neutralization potency with the goal of generating both accurate predictions of each activity based on antibody response profiles as well as insights into antibody mechanisms of action. To this end, antibody-mediated phagocytosis, cytotoxicity, complement deposition, and neutralization were accurately predicted from biophysical antibody profiles in both discovery and validation cohorts. These predictive models identified SARS-CoV-2-specific IgM as a key predictor of neutralization activity whose mechanistic relevance was supported experimentally by depletion. Validated models of how different aspects of the humoral response relate to antiviral antibody activities suggest desirable attributes to recapitulate by vaccination or other antibody-based interventions.

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Section: Discussionmentioning

confidence: 99%

Antibody Attributes that Predict the Neutralization and Effector Function of Polyclonal Responses to SARS-CoV-2

Natarajan

Crowley

et al. 2021

Preprint

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“…Memory B cells are increased 5-to 10-fold in hybrid immunity compared with natural infection or vaccination alone (3,12). Virus-specific CD4 + T cells and T FH cells appear to be key drivers of the recall and expansion of those SARS-CoV-2 memory B cells and the impressive antibody titers observed (13,14).…”

Section: The Chains Of Stress Recoverymentioning

confidence: 99%

“…Thus, the epitope breadth of both the CD4 + and CD8 + T cell responses is more restricted in current COVID-19 vaccines than in natural infection (1), whereas hybrid immunity consists of both spike and non-spike T cell memory. Notably, the Pfizer/BioNTech and Moderna COVID-19 messenger RNA (mRNA) vaccines can substantially boost spike CD4 + T cell responses in previously infected persons after one immunization (3,4,13,14). Differences in T cell responses after two doses of vaccine are more variable in those individuals (3,13).…”

Section: The Chains Of Stress Recoverymentioning

confidence: 99%

Hybrid immunity

Crotty

2021

Science

263

200

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“…Although the CD8 epitopes discussed in this section have originally been identified in infected and convalescent patients, available studies in vaccinees (43,(80)(81)(82)(83) confirm a substantial enrichment of CD8 T cell epitopes within the S2 domain, which contrasts with the lower CD8 epitope representation found in the S1 N-terminal domain (83).…”

Section: Cd8 T Cells In Anti-sars-cov-2 Protectionmentioning

confidence: 81%

Degenerate CD8 Epitopes Mapping to Structurally Constrained Regions of the Spike Protein: A T Cell-Based Way-Out From the SARS-CoV-2 Variants Storm

et al. 2021

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There is an urgent need for new generation anti-SARS-Cov-2 vaccines in order to increase the efficacy of immunization and its broadness of protection against viral variants that are continuously arising and spreading. The effect of variants on protective immunity afforded by vaccination has been mostly analyzed with regard to B cell responses. This analysis revealed variable levels of cross-neutralization capacity for presently available SARS-Cov-2 vaccines. Despite the dampened immune responses documented for some SARS-Cov-2 mutations, available vaccines appear to maintain an overall satisfactory protective activity against most variants of concern (VoC). This may be attributed, at least in part, to cell-mediated immunity. Indeed, the widely multi-specific nature of CD8 T cell responses should allow to avoid VoC-mediated viral escape, because mutational inactivation of a given CD8 T cell epitope is expected to be compensated by the persistent responses directed against unchanged co-existing CD8 epitopes. This is particularly relevant because some immunodominant CD8 T cell epitopes are located within highly conserved SARS-Cov-2 regions that cannot mutate without impairing SARS-Cov-2 functionality. Importantly, some of these conserved epitopes are degenerate, meaning that they are able to associate with different HLA class I molecules and to be simultaneously presented to CD8 T cell populations of different HLA restriction. Based on these concepts, vaccination strategies aimed at potentiating the stimulatory effect on SARS-Cov-2-specific CD8 T cells should greatly enhance the efficacy of immunization against SARS-Cov-2 variants. Our review recollects, discusses and puts into a translational perspective all available experimental data supporting these “hot” concepts, with special emphasis on the structural constraints that limit SARS-CoV-2 S-protein evolution and on potentially invariant and degenerate CD8 epitopes that lend themselves as excellent candidates for the rational development of next-generation, CD8 T-cell response-reinforced, COVID-19 vaccines.

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A single dose of the SARS-CoV-2 vaccine BNT162b2 elicits Fc-mediated antibody effector functions and T cell responses

Cited by 187 publications

References 100 publications

Antibody Attributes that Predict the Neutralization and Effector Function of Polyclonal Responses to SARS-CoV-2

Antibody Attributes that Predict the Neutralization and Effector Function of Polyclonal Responses to SARS-CoV-2

Hybrid immunity

Degenerate CD8 Epitopes Mapping to Structurally Constrained Regions of the Spike Protein: A T Cell-Based Way-Out From the SARS-CoV-2 Variants Storm

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