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.
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.
Kovacs-Nolan
J
J
Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, SK S7N 5E3, Canada.
Mapletoft
J W
JW
Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, SK S7N 5E3, Canada.
Lawman
Z
Z
Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, SK S7N 5E3, Canada.
Babiuk
L A
LA
University of Alberta, 3-7 University Hall, Edmonton, AB T6G 2J9, Canada.
van Drunen Littel-van den Hurk
S
S
Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, SK S7N 5E3, Canada.
D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D023181:Antimicrobial Cationic Peptides / Q000008:administration & dosage* / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D007074:Immunoglobulin G / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008168:Lung / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009500:Neutralization Tests; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage* / Q000494:pharmacology; D009943:Organophosphorus Compounds / Q000008:administration & dosage* / Q000494:pharmacology; D011108:Polymers / Q000008:administration & dosage* / Q000494:pharmacology; D018112:Respiratory Syncytial Virus, Bovine / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D014760:Viral Fusion Proteins / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D023181:Antimicrobial Cationic Peptides; C408982:CPG-oligonucleotide; D016207:Cytokines; D007074:Immunoglobulin G; D009838:Oligodeoxyribonucleotides; D009943:Organophosphorus Compounds; D011108:Polymers; D014760:Viral Fusion Proteins; C108974:poly(phosphazene); C073143:indolicidin