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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 (DeltaF). Mice immunized with DeltaF co-formulated with CpG ODN, indolicidin, and polyphosphazene (DeltaF/CpG/indol/PP) developed higher levels of DeltaF-specific serum IgG, IgG1 and IgG2a antibodies when compared with DeltaF 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 DeltaF/CpG/indol/PP developed significantly higher levels of BRSV-neutralizing serum antibodies than mice immunized with the DeltaF 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 DeltaF 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.

journal of general virology

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