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.
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.
Du
Lanying
L
Department of Microbiology, University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China.
Zhao
Guangyu
G
Lin
Yongping
Y
Sui
Hongyan
H
Chan
Chris
C
Ma
Selene
S
He
Yuxian
Y
Jiang
Shibo
S
Wu
Changyou
C
Yuen
Kwok-Yung
KY
Jin
Dong-Yan
DY
Zhou
Yusen
Y
Zheng
Bo-Jian
BJ
D000281:Administration, Intranasal; D000818:Animals; D000917:Antibody Formation; D041702:BALB 3T3 Cells; D000229:Dependovirus / Q000235:genetics; D006801:Humans; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000276:immunology; D008168:Lung / Q000276:immunology; D008562:Membrane Glycoproteins / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology*; D051379:Mice; D045473:Severe acute respiratory syndrome-related coronavirus / Q000187:drug effects / Q000502:physiology; D045169:Severe Acute Respiratory Syndrome / Q000517:prevention & control*; D064370:Spike Glycoprotein, Coronavirus; D013154:Spleen / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014611:Vaccination; D014759:Viral Envelope Proteins / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology*; D014765:Viral Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology*; D014779:Virus Replication / Q000187:drug effects
D007070:Immunoglobulin A; D008562:Membrane Glycoproteins; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins; D014765:Viral Vaccines