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

¹ University of Guelph;
² University of Saskatchewan

³ E-mail: sylvia.vandenhurk{at}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 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 to F alone, and displayed an increase in the frequency of IFN--secreting cells and decreased IL-5 production by in vitro re-stimulated 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 defense 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.

Received 8 March 2009; accepted 17 April 2009.