CVI Accepts, published online ahead of print on 28 October 2009

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Clin. Vaccine Immunol. doi:10.1128/CVI.00250-09
Copyright (c) 2009, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Intranasal immunization of mice with a bovine respiratory syncytial virus vaccine induces superior immunity and protection in comparison to subcutaneous delivery or combinations of intranasal and subcutaneous prime-boost strategies

John W. Mapletoft, Laura Latimer, Lorne A. Babiuk, and Sylvia van Drunen Littel-van den Hurk^*

Vaccine & Infectious Disease Organization and Microbiology and Immunology, University of Saskatchewan, 120 Veterinary Road, Saskatoon, Saskatchewan S7N 5E3, Canada; Office of the Vice-President (Research), University of Alberta, 3rd Floor University Hall, Edmonton, Alberta T6G 2J9, Canada

^* To whom correspondence should be addressed. Email: sylvia.vandenhurk{at}usask.ca.

Bovine respiratory syncytial virus (BRSV) infects cells of the respiratory mucosa, so it is desirable to develop a vaccination strategy that induces mucosal immunity. To achieve this, various delivery routes were compared for formalin-inactivated (FI)-BRSV formulated with CpG oligodeoxynucleotide (ODN) and polyphosphazene (PP). Intranasal delivery of the FI-BRSV formulation was superior to subcutaneous delivery in terms of antibody, cell-mediated and mucosal immune responses, as well as reduction in virus replication after BRSV challenge. Although intranasal delivery of FI-BRSV also induced higher serum and lung antibody titers and IFN- production in the lungs than intranasal-subcutaneous and/or subcutaneous-intranasal prime-boost strategies, no significant differences were observed in cell-mediated immune responses or virus replication in the lungs of challenged mice. IL-5, eotaxin and eosinophilia were enhanced after BRSV challenge in the lungs of subcutaneously immunized mice when compared to unvaccinated mice, but not in the lungs of mice immunized intranasally or through combinations of intranasal and subcutaneous routes. These results suggest that two intranasal immunizations with FI-BRSV formulated with CpG ODN and PP are effective and safe as an approach to induce systemic and mucosal responses, as well reduce virus replication after BRSV challenge. Furthermore, intranasal-subcutaneous and subcutaneous-intranasal prime-boost strategies were also safe, and almost as efficacious. In addition to the implications for the development of a protective BRSV vaccine for cattle, formulation with CpG ODN and PP could also prove important in the development of a mucosal vaccine that induces protective immunity against human RSV.