RCT Abstract - Ad26.COV2.S induces SARS-CoV-2 spike protein-specific cellular immunity and humoral immune responses that cover variants of concern

Abstract Objectives. The efficiency of Covid-19 vaccination is determined by cellular and humoral immune responses, and for the latter, by the balance between neutralizing and infection-enhancing antibodies. Here we analyzed the evolution of neutralizing and facilitating epitopes in the spike protein among SARS-CoV-2 variants. Methods. Amino acid alignments were performed on 929,203 spike sequences over the 4 last months. Molecular modeling studies of the N-terminal domain (NTD) and rod-like regions of the spike protein were performed on a representative panel of SARS-CoV-2 variants that were structurally compared with the original Wuhan strain. Results. D614, which belongs to an antibody-dependent-enhancement (ADE) epitope common to SARS-CoV-1 and SARS-CoV-2, has rapidly mutated to D614G in the first months of 2020, explaining why ADE has not been detected following mass vaccination. We show that this epitope is conformationally linked to the main ADE epitope of the SARS-CoV-2 NTD which is highly conserved among most variants. In contrast, the neutralizing epitope of the NTD showed extensive variations in SARS-CoV-2 variants. Conclusions. This molecular epidemiology study coupled with structural analysis of the spike protein indicates that the balance between facilitating and neutralizing antibodies in vaccinated people is in favor of neutralization for the Wuhan strain,alpha and beta variants, but not for gamma, delta, lambda and mu. The evolution of SARS-CoV-2 has dramatically affected the ADE/neutralization balance which is nowadays in favor of ADE. Future vaccines should consider these data to design new formulations adapted to SARS-CoV-2 variants and lacking ADE epitopes in the spike protein.

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Humoral immune responses during SARS-CoV-2 mRNA vaccine administration in seropositive and seronegative individuals

BMC Medicine ◽

10.1186/s12916-021-02055-9 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Elizabeth Fraley ◽

Cas LeMaster ◽

Eric Geanes ◽

Dithi Banerjee ◽

Santosh Khanal ◽

...

Keyword(s):

Immune Responses ◽

Messenger Rna ◽

Antibody Responses ◽

Spike Protein ◽

Prior History ◽

Antibody Isotype ◽

Humoral Immune ◽

Humoral Immune Responses ◽

History Of ◽

Antibody Levels

Abstract Background The global pandemic of coronavirus disease 2019 (COVID-19) is caused by infection with the SARS-CoV-2 virus. Currently, there are three approved vaccines against SARS-CoV-2 in the USA, including two based on messenger RNA (mRNA) technology that has demonstrated high vaccine efficacy. We sought to characterize humoral immune responses, at high resolution, during immunization with the BNT162b2 (Pfizer-BioNTech) vaccine in individuals with or without prior history of natural SARS-CoV-2 infection. Methods We determined antibody responses after each dose of the BNT162b2 SARS-CoV-2 vaccine in individuals who had no prior history of SARS-CoV-2 infection (seronegative) and individuals that had previous viral infection 30–60 days prior to first vaccination (seropositive). To do this, we used both an antibody isotype-specific multiplexed bead-based binding assays targeting multiple SARS-CoV-2 viral protein antigens and an assay that identified potential SARS-CoV-2 neutralizing antibody levels. Moreover, we mapped antibody epitope specificity after immunization using SARS-CoV-2 spike protein peptide arrays. Results Antibody levels were significantly higher after a single dose in seropositive individuals compared to seronegative individuals and were comparable to levels observed in seronegative individuals after two doses. While IgG was boosted by vaccination for both seronegative and seropositive individuals, only seronegative individuals had increased IgA or IgM antibody titers after primary immunization. We identified immunodominant peptides targeted on both SARS-CoV-2 spike S1 and S2 subunits after vaccination. Conclusion These findings demonstrated the antibody responses to SARS-CoV-2 immunization in seropositive and seronegative individuals and provide support for the concept of using prior infection history as a guide for the consideration of future vaccination regimens. Moreover, we identified key epitopes on the SARS-CoV-2 spike protein that are targeted by antibodies after vaccination that could guide future vaccine and immune correlate development.

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Distinct evolution of infection-enhancing and neutralizing epitopes in the spike protein of SARS-CoV-2 variants (alpha, beta, gamma, delta, lambda and µ) : a structural and molecular epidemiology study

10.22541/au.163638609.95446888/v1 ◽

2021 ◽

Author(s):

Patrick Guérin ◽

Nouara Yahi ◽

Fodil Azzaz ◽

Henri Chahinian ◽

Jean-Marc Sabatier ◽

...

Keyword(s):

Immune Responses ◽

Molecular Epidemiology ◽

Neutralizing Antibodies ◽

Spike Protein ◽

Epidemiology Study ◽

Gamma Delta ◽

Humoral Immune ◽

Humoral Immune Responses ◽

Spike Sequences ◽

Molecular Modeling Studies

Objectives. The efficiency of Covid-19 vaccination is determined by cellular and humoral immune responses, and for the latter, by the balance between neutralizing and infection-enhancing antibodies. Here we analyzed the evolution of neutralizing and facilitating epitopes in the spike protein among SARS-CoV-2 variants. Methods. Amino acid alignments were performed on 929,203 spike sequences over the 4 last months. Molecular modeling studies of the N-terminal domain (NTD) and rod-like regions of the spike protein were performed on a representative panel of SARS-CoV-2 variants that were structurally compared with the original Wuhan strain. Results. D614, which belongs to an antibody-dependent-enhancement (ADE) epitope common to SARS-CoV-1 and SARS-CoV-2, has rapidly mutated to D614G in the first months of 2020, explaining why ADE has not been detected following mass vaccination. We show that this epitope is conformationally linked to the main ADE epitope of the SARS-CoV-2 NTD which is highly conserved among most variants. In contrast, the neutralizing epitope of the NTD showed extensive variations in SARS-CoV-2 variants. Conclusions. This molecular epidemiology study coupled with structural analysis of the spike protein indicates that the balance between facilitating and neutralizing antibodies in vaccinated people is in favor of neutralization for the Wuhan strain, alpha and beta variants, but not for gamma, delta, lambda and mu. The evolution of SARS-CoV-2 has dramatically affected the ADE/neutralization balance which is nowadays in favor of ADE. Future vaccines should consider these data to design new formulations adapted to SARS-CoV-2 variants and lacking ADE epitopes in the spike protein.

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Evaluation of Cellular Immunity with ASFV Infection by Swine Leukocyte Antigen (SLA)—Peptide Tetramers

Viruses ◽

10.3390/v13112264 ◽

2021 ◽

Vol 13 (11) ◽

pp. 2264

Author(s):

Wenqiang Sun ◽

He Zhang ◽

Wenhui Fan ◽

Lihong He ◽

Teng Chen ◽

...

Keyword(s):

T Cell ◽

Immune Responses ◽

Cellular Immunity ◽

African Swine Fever Virus ◽

Economic Losses ◽

Cell Immune Response ◽

Swine Leukocyte Antigen ◽

Leukocyte Antigen ◽

Humoral Immune ◽

Humoral Immune Responses

African swine fever virus (ASFV) causes acute hemorrhagic fever in domestic pigs and wild boars, resulting in incalculable economic losses to the pig industry. As the mechanism of viral infection is not clear, protective antigens have not been discovered or identified. In this study, we determined that the p30, pp62, p72, and CD2v proteins were all involved in the T cell immune response of live pigs infected with ASFV, among which p72 and pp62 proteins were the strongest. Panoramic scanning was performed on T cell epitopes of the p72 protein, and three high-frequency positive epitopes were selected to construct a swine leukocyte antigen (SLA)-tetramer, and ASFV-specific T cells were detected. Subsequently, the specific T cell and humoral immune responses of ASFV-infected pigs and surviving pigs were compared. The results demonstrate that the specific T cellular immunity responses gradually increased during the infection and were higher than that in the surviving pigs in the late stages of infection. The same trend was observed in specific humoral immune responses, which were highest in surviving pigs. In general, our study provides key information for the exploration of ASFV-specific immune responses and the development of an ASFV vaccine.

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