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Priming with rAAV encoding RBD of SARS-CoV S protein and boosting with RBD-specific peptides for T cell epitopes elevated humoral and cellular immune responses against SARS-CoV infection

Identifieur interne : 003479 ( Main/Exploration ); précédent : 003478; suivant : 003480

Priming with rAAV encoding RBD of SARS-CoV S protein and boosting with RBD-specific peptides for T cell epitopes elevated humoral and cellular immune responses against SARS-CoV infection

Auteurs : LANYING DU [Hong Kong, États-Unis] ; GUANGYU ZHAO [République populaire de Chine] ; YONGPING LIN [Hong Kong] ; CHRIS CHAN [Hong Kong] ; YUXIAN HE [États-Unis] ; SHIBO JIANG [États-Unis] ; CHANGYOU WU [République populaire de Chine] ; Dong-Yan Jin [Hong Kong] ; Kwok-Yung Yuen [Hong Kong] ; YUSEN ZHOU [République populaire de Chine] ; Bo-Jian Zheng [Hong Kong]

Source :

RBID : Pascal:08-0427329

Descripteurs français

English descriptors

Abstract

Development of vaccines against severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) is crucial in the prevention of SARS reemergence. The receptor-binding domain (RBD) of SARS-CoV spike (S) protein is an important target in developing safe and effective SARS vaccines. Our previous study has demonstrated that vaccination with adenoassociated virus encoding RBD (RBD-rAAV) induces high titer of neutralizing antibodies. In this study, we further assessed the immune responses and protective effect of the immunization with RBD-rAAV prime/RBD-specific T cell peptide boost. Compared with the RBD-rAAV prime/boost vaccination, RBD-rAAV prime/RBD-peptide (RBD-Pep) boost induced similar levels of Th1 and neutralizing antibody responses that protected the vaccinated mice from subsequent SARS-CoV challenge, but stronger Th2 and CTL responses. No significant immune responses and protective effects were detected in mice vaccinated with RBD-Pep or blank AAV alone. Since T cell epitopes are highly conserved and boosting with peptides may induce the production of effector memory T cells, which may be effective against viruses with mutations in the neutralizing epitopes, our results suggest that the vaccination protocol used may be ideal for providing effective, broad and long-term protection against SARS-CoV infection.


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Le document en format XML

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<div type="abstract" xml:lang="en">Development of vaccines against severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) is crucial in the prevention of SARS reemergence. The receptor-binding domain (RBD) of SARS-CoV spike (S) protein is an important target in developing safe and effective SARS vaccines. Our previous study has demonstrated that vaccination with adenoassociated virus encoding RBD (RBD-rAAV) induces high titer of neutralizing antibodies. In this study, we further assessed the immune responses and protective effect of the immunization with RBD-rAAV prime/RBD-specific T cell peptide boost. Compared with the RBD-rAAV prime/boost vaccination, RBD-rAAV prime/RBD-peptide (RBD-Pep) boost induced similar levels of Th1 and neutralizing antibody responses that protected the vaccinated mice from subsequent SARS-CoV challenge, but stronger Th2 and CTL responses. No significant immune responses and protective effects were detected in mice vaccinated with RBD-Pep or blank AAV alone. Since T cell epitopes are highly conserved and boosting with peptides may induce the production of effector memory T cells, which may be effective against viruses with mutations in the neutralizing epitopes, our results suggest that the vaccination protocol used may be ideal for providing effective, broad and long-term protection against SARS-CoV infection.</div>
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