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Open Access Research

Sublingual immunization with recombinant adenovirus encoding SARS-CoV spike protein induces systemic and mucosal immunity without redirection of the virus to the brain

Byoung-Shik Shim12, Konrad Stadler1, Huan Huu Nguyen1, Cheol-Heui Yun2, Dong Wook Kim3, Jun Chang4, Cecil Czerkinsky1 and Man Ki Song1*

Author Affiliations

1 Laboratory Sciences Division, International Vaccine Institute, Seoul, 151-919, Republic of Korea

2 Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, and the Center for Agricultural Biomaterials, and Center for Food Safety and Toxicology, Seoul National University, Seoul, 151-921, Republic of Korea

3 Department of Pharmacy, College of Pharmacy, Hanyang University, Kyeonggi-do, 426-791, Republic of Korea

4 College of Pharmacy, Ewha Womans University, 11-1 Dae-Hyun Dong, Seo-Dae-Mun Gu, Seoul, 120-750, Republic of Korea

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Virology Journal 2012, 9:215  doi:10.1186/1743-422X-9-215

Published: 21 September 2012

Abstract

Background

Sublingual (s.l.) administration of soluble protein antigens, inactivated viruses, or virus-like particles has been shown to induce broad immune responses in mucosal and extra-mucosal tissues. Recombinant replication-defective adenovirus vectors (rADVs) infect mucosa surface and therefore can serve as a mucosal antigen delivery vehicle. In this study we examined whether s.l. immunization with rADV encoding spike protein (S) (rADV-S) of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) induces protective immunity against SARS-CoV and could serve as a safe mucosal route for delivery of rADV.

Results

Here, we show that s.l. administration of rADV-S induced serum SARS-CoV neutralizing and airway IgA antibodies in mice. These antibody responses are comparable to those induced by intranasal (i.n.) administration. In addition, s.l. immunization induced antigen-specific CD8+ T cell responses in the lungs that are superior to those induced by intramuscular immunization. Importantly, unlike i.n. administration, s.l. immunization with rADV did not redirect the rADV vector to the olfactory bulb.

Conclusion

Our study indicates that s.l. immunization with rADV-S is safe and effective in induction of a broad spectrum of immune responses and presumably protection against infection with SARS-CoV.

Keywords:
Recombinant adenovirus; Sublingual administration; Severe acute respiratory syndrome; Mucosa; T cell; IgA