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Intranasal vaccination of recombinant adeno-associated virus encoding receptor-binding domain of severe acute respiratory syndrome coronavirus (SARS-CoV) spike protein induces strong mucosal immune responses and provides long-term protection against SARS-CoV infection.

Identifieur interne : 003086 ( Main/Exploration ); précédent : 003085; suivant : 003087

Intranasal vaccination of recombinant adeno-associated virus encoding receptor-binding domain of severe acute respiratory syndrome coronavirus (SARS-CoV) spike protein induces strong mucosal immune responses and provides long-term protection against SARS-CoV infection.

Auteurs : Lanying Du [République populaire de Chine] ; Guangyu Zhao ; Yongping Lin ; Hongyan Sui ; Chris Chan ; Selene Ma ; Yuxian He ; Shibo Jiang ; Changyou Wu ; Kwok-Yung Yuen ; Dong-Yan Jin ; Yusen Zhou ; Bo-Jian Zheng

Source :

RBID : pubmed:18178835

Descripteurs français

English descriptors

Abstract

We have previously reported that a subunit protein vaccine based on the receptor-binding domain (RBD) of severe acute respiratory syndrome coronavirus (SARS-CoV) spike protein and a recombinant adeno-associated virus (rAAV)-based RBD (RBD-rAAV) vaccine could induce highly potent neutralizing Ab responses in immunized animals. In this study, systemic, mucosal, and cellular immune responses and long-term protective immunity induced by RBD-rAAV were further characterized in a BALB/c mouse model, with comparison of the i.m. and intranasal (i.n.) routes of administration. Our results demonstrated that: 1) the i.n. vaccination induced a systemic humoral immune response of comparable strength and shorter duration than the i.m. vaccination, but the local humoral immune response was much stronger; 2) the i.n. vaccination elicited stronger systemic and local specific cytotoxic T cell responses than the i.m. vaccination, as evidenced by higher prevalence of IL-2 and/or IFN-gamma-producing CD3+/CD8+ T cells in both lungs and spleen; 3) the i.n. vaccination induced similar protection as the i.m. vaccination against SARS-CoV challenge in mice; 4) higher titers of mucosal IgA and serum-neutralizing Ab were associated with lower viral load and less pulmonary pathological damage, while no Ab-mediated disease enhancement effect was observed; and 5) the vaccination could provide long-term protection against SARS-CoV infection. Taken together, our findings suggest that RBD-rAAV can be further developed into a vaccine candidate for prevention of SARS and that i.n. vaccination may be the preferred route of administration due to its ability to induce SARS-CoV-specific systemic and mucosal immune responses and its better safety profile.

DOI: 10.4049/jimmunol.180.2.948
PubMed: 18178835


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<term>BALB 3T3 Cells</term>
<term>Dependovirus (genetics)</term>
<term>Humans</term>
<term>Immunity, Mucosal</term>
<term>Immunoglobulin A (immunology)</term>
<term>Lung (immunology)</term>
<term>Membrane Glycoproteins (administration & dosage)</term>
<term>Membrane Glycoproteins (genetics)</term>
<term>Membrane Glycoproteins (immunology)</term>
<term>Mice</term>
<term>SARS Virus (drug effects)</term>
<term>SARS Virus (physiology)</term>
<term>Severe Acute Respiratory Syndrome (prevention & control)</term>
<term>Spike Glycoprotein, Coronavirus</term>
<term>Spleen (immunology)</term>
<term>T-Lymphocytes, Cytotoxic (immunology)</term>
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<term>Viral Envelope Proteins (genetics)</term>
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<term>Dependovirus (génétique)</term>
<term>Glycoprotéine de spicule des coronavirus</term>
<term>Glycoprotéines membranaires (administration et posologie)</term>
<term>Glycoprotéines membranaires (génétique)</term>
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<term>Immunité muqueuse</term>
<term>Immunoglobuline A (immunologie)</term>
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<term>Protéines de l'enveloppe virale (immunologie)</term>
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<term>Vaccins antiviraux (génétique)</term>
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<term>Protéines de l'enveloppe virale</term>
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<term>Vaccins antiviraux</term>
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<front>
<div type="abstract" xml:lang="en">We have previously reported that a subunit protein vaccine based on the receptor-binding domain (RBD) of severe acute respiratory syndrome coronavirus (SARS-CoV) spike protein and a recombinant adeno-associated virus (rAAV)-based RBD (RBD-rAAV) vaccine could induce highly potent neutralizing Ab responses in immunized animals. In this study, systemic, mucosal, and cellular immune responses and long-term protective immunity induced by RBD-rAAV were further characterized in a BALB/c mouse model, with comparison of the i.m. and intranasal (i.n.) routes of administration. Our results demonstrated that: 1) the i.n. vaccination induced a systemic humoral immune response of comparable strength and shorter duration than the i.m. vaccination, but the local humoral immune response was much stronger; 2) the i.n. vaccination elicited stronger systemic and local specific cytotoxic T cell responses than the i.m. vaccination, as evidenced by higher prevalence of IL-2 and/or IFN-gamma-producing CD3+/CD8+ T cells in both lungs and spleen; 3) the i.n. vaccination induced similar protection as the i.m. vaccination against SARS-CoV challenge in mice; 4) higher titers of mucosal IgA and serum-neutralizing Ab were associated with lower viral load and less pulmonary pathological damage, while no Ab-mediated disease enhancement effect was observed; and 5) the vaccination could provide long-term protection against SARS-CoV infection. Taken together, our findings suggest that RBD-rAAV can be further developed into a vaccine candidate for prevention of SARS and that i.n. vaccination may be the preferred route of administration due to its ability to induce SARS-CoV-specific systemic and mucosal immune responses and its better safety profile.</div>
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