Intranasal Immunization of Mice with a Bovine Respiratory Syncytial Virus Vaccine Induces Superior Immunity and Protection Compared to Those by Subcutaneous Delivery or Combinations of Intranasal and Subcutaneous Prime-Boost Strategies
- 1 January 2010
- journal article
- research article
- Published by American Society for Microbiology in Clinical and Vaccine Immunology
- Vol. 17 (1), 23-35
- https://doi.org/10.1128/cvi.00250-09
Abstract
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 gamma interferon (IFN-γ) 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. Interleukin 5 (IL-5), eotaxin, and eosinophilia were enhanced after BRSV challenge in the lungs of subcutaneously immunized mice compared to unvaccinated mice, but not in the lungs of mice immunized intranasally or through combinations of the 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 to 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.Keywords
This publication has 54 references indexed in Scilit:
- Lack of antibody affinity maturation due to poor Toll-like receptor stimulation leads to enhanced respiratory syncytial virus diseaseNature Medicine, 2008
- Co-administration of polyphosphazenes with CpG oligodeoxynucleotides strongly enhances immune responses in mice immunized with Hepatitis B virus surface antigenVaccine, 2008
- Bovine respiratory syncytial virus infection: immunopathogenic mechanismsAnimal Health Research Reviews, 2007
- Poly[di(sodium carboxylatoethylphenoxy)phosphazene] (PCEP) is a potent enhancer of mixed Th1/Th2 immune responses in mice immunized with influenza virus antigensVaccine, 2007
- Protection against Aerosolized Yersinia pestis Challenge following Homologous and Heterologous Prime-Boost with Recombinant Plague AntigensInfection and Immunity, 2005
- Effect of homologous and heterologous prime–boost on the immune response to recombinant plague antigensVaccine, 2005
- Synthesis and Biologically Relevant Properties of Polyphosphazene PolyacidsBiomacromolecules, 2004
- Mucosal Immunization with Inactivated Human Immunodeficiency Virus plus CpG Oligodeoxynucleotides Induces Genital Immune Responses and Protection against Intravaginal ChallengeThe Journal of Infectious Diseases, 2002
- Evaluation of Cholera Vaccines Formulated with Toxin-Coregulated Pilin Peptide Plus Polymer Adjuvant in MiceInfection and Immunity, 2001
- Respiratory syncytial virusArchiv für die gesamte Virusforschung, 1985