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 Shim,Cheol-Heui Yun,Dong Wook Kim,Jun Chang,Konrad Stadler,Man Ki Song,Huan Huu Nguyen,Cecil Czerkinsky

doi:10.1186/1743-422x-9-215

Abstract

BackgroundSublingual (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.ResultsHere, 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.ConclusionOur 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.

Highlights

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
Characterization of route and onlyReplication-defective adenovirus (rADV) expressing SARS-CoV S protein To confirm the expression of S protein in vitro, 293 cells were infected with replication-defective ADV encoding truncated S protein (rADV-S) at 20 multiplicity of infection (MOI) for 48 hrs
Administration of rADV induced mucosal Ab responses To compare the immune responses induced by different delivery routes, we immunized s.l., i.n., or i.m. each group of BALB/c mice three times 14 days apart with either 2 × 107 or 1 × 108 plaque-forming unit (PFU) of rADV-S

Summary

Introduction

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 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. The majority of microbial pathogens enter their hosts through a mucosal site; effective vaccines should elicit immune responses at the site of infection [1,2]. Vaccines against pathogens such as severe acute respiratory syndrome-associated coronavirus (SARS-CoV) which infects the airways should elicit immune responses in the mucosa of the respiratory tract [3]. ADVs infect their host through the airway epithelium, and replicate in mucosal tissues of the respiratory tracts [21].

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Results

Conclusion