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The Cross-Protective Immunity Landscape Among Different SARS-CoV-2 Variant RBDs.

ABSTRACT: Despite the fact that SARS-CoV-2 vaccines have been available in most parts of the world, the epidemic status remains grim with new variants emerging and escaping the immune protection of existing vaccines. Therefore, the development of more effective antigens and evaluation of their cross-protective immunity against different SARS-CoV-2 variants are particularly urgent. In this study, we expressed the wild type (WT), Alpha, Beta, Delta, and Lambda RBD proteins to immunize mice and evaluated their cross-neutralizing activity against different pseudoviruses (WT, Alpha, Beta, Delta, Lambda, and Omicron). All monovalent and pentavalent RBD antigens induced high titers of IgG antibodies against different variant RBD antigens. In contrast, WT RBD antigen-induced antibodies showed a lower neutralizing activity against Beta, Delta, Lambda, and Omicron pseudoviruses compared to neutralization against itself. Interestingly, Beta RBD antigen and multivalent antigen induced broader cross-neutralization antibodies than other variant RBD antigens. These data provide a reference for vaccine strain selection and universal COVID-19 vaccine design to fight the constant emergence of new SARS-CoV-2 variants.

SUBMITTER: Sun W

PROVIDER: S-EPMC9226324 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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The Cross-Protective Immunity Landscape Among Different SARS-CoV-2 Variant RBDs.

Sun Wenqiang W He Lihong L Lou Huicong H Fan Wenhui W Yang Limin L Cheng Gong G Liu Wenjun W Sun Lei L

Frontiers in immunology 20220610

Despite the fact that SARS-CoV-2 vaccines have been available in most parts of the world, the epidemic status remains grim with new variants emerging and escaping the immune protection of existing vaccines. Therefore, the development of more effective antigens and evaluation of their cross-protective immunity against different SARS-CoV-2 variants are particularly urgent. In this study, we expressed the wild type (WT), Alpha, Beta, Delta, and Lambda RBD proteins to immunize mice and evaluated the ...[more]

PMID: 35757743

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Project description:Numerous clinical parameters link to severe coronavirus disease 2019, but factors that prevent symptomatic disease remain unknown. We investigated the impact of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) and endemic human coronavirus (HCoV) antibody responses on symptoms in a longitudinal children cohort (n = 2,917) and a cross-sectional cohort including children and adults (n = 882), all first exposed to SARS-CoV-2 (March 2020 to March 2021) in Switzerland. Saliva (n = 4,993) and plasma (n = 7,486) antibody reactivity to the four HCoVs (subunit S1 [S1]) and SARS-CoV-2 (S1, receptor binding domain, subunit S2 [S2], nucleocapsid protein) was determined along with neutralizing activity against SARS-CoV-2 Wuhan, Alpha, Delta, and Omicron (BA.2) in a subset of individuals. Inferred recent SARS-CoV-2 infection was associated with a strong correlation between mucosal and systemic SARS-CoV-2 anti-spike responses. Individuals with pre-existing HCoV-S1 reactivity exhibited significantly higher antibody responses to SARS-CoV-2 in both plasma (IgG regression coefficients = 0.20, 95% CI = [0.09, 0.32], P < 0.001) and saliva (IgG regression coefficient = 0.60, 95% CI = [0.088, 1.11], P = 0.025). Saliva neutralization activity was modest but surprisingly broad, retaining activity against Wuhan (median NT50 = 32.0, 1Q-3Q = [16.4, 50.2]), Alpha (median NT50 = 34.9, 1Q-3Q = [26.0, 46.6]), and Delta (median NT50 = 28.0, 1Q-3Q = [19.9, 41.7]). In line with a rapid mucosal defense triggered by cross-reactive HCoV immunity, asymptomatic individuals presented with higher pre-existing HCoV-S1 activity in plasma (IgG HKU1, odds ratio [OR] = 0.53, 95% CI = [0.29,0.97], P = 0.038) and saliva (total HCoV, OR = 0.55, 95% CI = [0.33, 0.91], P = 0.019) and higher SARS-CoV-2 reactivity in saliva (IgG S2 fold change = 1.26, 95% CI = [1.03, 1.54], P = 0.030). By investigating the systemic and mucosal immune responses to SARS-CoV-2 and HCoVs in a population without prior exposure to SARS-CoV-2 or vaccination, we identified specific antibody reactivities associated with lack of symptom development.IMPORTANCEKnowledge of the interplay between human coronavirus (HCoV) immunity and severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection is critical to understanding the coexistence of current endemic coronaviruses and to building knowledge potential future zoonotic coronavirus transmissions. This study, which retrospectively analyzed a large cohort of individuals first exposed to SARS-CoV-2 in Switzerland in 2020-2021, revealed several key findings. Pre-existing HCoV immunity, particularly mucosal antibody responses, played a significant role in improving SARS-CoV-2 immune response upon infection and reducing symptoms development. Mucosal neutralizing activity against SARS-CoV-2, although low in magnitude, retained activity against SARS-CoV-2 variants underlining the importance of maintaining local mucosal immunity to SARS-CoV-2. While the cross-protective effect of HCoV immunity was not sufficient to block infection by SARS-CoV-2, the present study revealed a remarkable impact on limiting symptomatic disease. These findings support the feasibility of generating pan-protective coronavirus vaccines by inducing potent mucosal immune responses.

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The Cross-Protective Immunity Landscape Among Different SARS-CoV-2 Variant RBDs.

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The Cross-Protective Immunity Landscape Among Different SARS-CoV-2 Variant RBDs.

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