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.
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 adeno-associated 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.
Du
Lanying
L
Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
Zhao
Guangyu
G
Lin
Yongping
Y
Chan
Chris
C
He
Yuxian
Y
Jiang
Shibo
S
Wu
Changyou
C
Jin
Dong-Yan
DY
Yuen
Kwok-Yung
KY
Zhou
Yusen
Y
Zheng
Bo-Jian
BJ
D000818:Animals; D000917:Antibody Formation / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D000086862:Coronavirus M Proteins; D000229:Dependovirus / Q000235:genetics* / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D007111:Immunity, Cellular / Q000276:immunology*; D007115:Immunization Schedule; D007117:Immunization, Secondary; D007074:Immunoglobulin G / Q000032:analysis / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D011991:Receptors, Virus / Q000235:genetics* / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D045473:Severe acute respiratory syndrome-related coronavirus / Q000276:immunology*; D045169:Severe Acute Respiratory Syndrome / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D013601:T-Lymphocytes / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology; D014763:Viral Matrix Proteins / Q000235:genetics* / Q000276:immunology*; D014765:Viral Vaccines / Q000276:immunology*
D000086862:Coronavirus M Proteins; D000939:Epitopes; D007074:Immunoglobulin G; C000706237:M protein, SARS-CoV; D011991:Receptors, Virus; D014614:Vaccines, Synthetic; D014763:Viral Matrix Proteins; D014765:Viral Vaccines