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This Article Full Text Full Text (PDF) Supplementary Table All Versions of this Article: vir.0.011684-0v1 90/8/1892    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via CrossRef Google Scholar Articles by Kovacs-Nolan, J. Articles by van Drunen Littel-van den Hurk, S. PubMed PubMed Citation Articles by Kovacs-Nolan, J. Articles by van Drunen Littel-van den Hurk, S. Agricola Articles by Kovacs-Nolan, J. Articles by van Drunen Littel-van den Hurk, S.

Formulation of bovine respiratory syncytial virus fusion protein with CpG oligodeoxynucleotide, cationic host defence peptide and polyphosphazene enhances humoral and cellular responses and induces a protective type 1 immune response in mice

¹ Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, SK S7N 5E3, Canada
² University of Alberta, 3–7 University Hall, Edmonton, AB T6G 2J9, Canada

Correspondence
S. van Drunen Littel-van den Hurksylvia.vandenhurk@usask.ca

Respiratory syncytial virus (RSV) is the leading cause of serious respiratory tract disease in children and calves; however, RSV vaccine development has been slow due to early observations that formalin-inactivated vaccines induced Th2-type immune responses and led to disease enhancement upon subsequent exposure. Hence, there is a need for novel adjuvants that will promote a protective Th1-type or balanced immune response against RSV. CpG oligodeoxynucleotides (ODNs), indolicidin, and polyphosphazene were examined for their ability to enhance antigen-specific immune responses and influence the Th-bias when co-formulated with a recombinant truncated bovine RSV (BRSV) fusion protein (F). Mice immunized with F co-formulated with CpG ODN, indolicidin, and polyphosphazene (F/CpG/indol/PP) developed higher levels of F-specific serum IgG, IgG1 and IgG2a antibodies when compared with F alone, and displayed an increase in the frequency of gamma interferon-secreting cells and decreased interleukin (IL)-5 production by in vitro restimulated splenocytes, characteristic of a Th1 immune response. These results were observed in both C57BL/6 and BALB/c strains of mice. When evaluated in a BRSV challenge model, mice immunized with F/CpG/indol/PP developed significantly higher levels of BRSV-neutralizing serum antibodies than mice immunized with the F protein alone, and displayed significantly less pulmonary IL-4, IL-5, IL-13 and eotaxin and reduced eosinophilia after challenge. These results suggest that co-formulation of F with CpG ODN, host defence peptide and polyphosphazene may result in a safe and effective vaccine for the prevention of BRSV and may have implications for the development of novel human RSV vaccines.

A supplementary table showing F-specific IgG1 and IgG2a titres after two immunizations and after challenge with BRSV is available with the online version of this paper.