title: CpG containing oligodeoxynucleotides are potent adjuvants for parenteral vaccination with the fusion (F) protein of respiratory syncytial virus (RSV).
abstract: The feasibility of using oligodeoxynucleotides (ODN) containing unmethylated CpG motifs as parenteral adjuvants for subunit vaccines against RSV was tested in BALB/c mice. Compared with immunization with natural F protein adsorbed to aluminum hydroxide (F/AlOH) adjuvant alone, coadministration of F/AlOH with CpG ODN resulted in statistically significant increases in serum neutralization titers, an enhanced generation of splenic antigen-dependent killer cell precursors, and accelerated clearance of infectious virus from lungs 4 days after challenge. The statistically significant increases in serum IFNgamma and anti-F protein IgG2a titers, and significantly diminished pulmonary IL-5 and eosinophilia after challenge indicated that CpG ODN enhanced the ability of F/AlOH to elicit type 1 immune responses. F protein-specific serum IgE titers were also reduced. Further analysis of pulmonary inflammatory cells demonstrated an expansion of CD8(+) T cells, relative to the CD4(+) T cell compartment. The potency of CpG ODN was not adversely affected in gene knockout mice devoid of the p35 chain of the IL-12 heterodimer. Taken together, the results suggest a novel formulation for naïve recipients of F protein-based subunit vaccines that does not result in a type 2 phenotype.
authors.affiliation: Department of Immunology Research, Wyeth-Lederle Vaccines, 211 Bailey Road, West Henrietta, NY 14586, USA. hancocg@war.wyeth.com
authors.forename: G E
authors.initials: GE
authors.lastname: Hancock
authors.forename: K M
authors.initials: KM
authors.lastname: Heers
authors.forename: J D
authors.initials: JD
authors.lastname: Smith
authors.forename: C A
authors.initials: CA
authors.lastname: Scheuer
authors.forename: A R
authors.initials: AR
authors.lastname: Ibraghimov
authors.forename: K S
authors.initials: KS
authors.lastname: Pryharski
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis* / Q000097:blood / Q000276:immunology; D000918:Antibody Specificity; D018899:CpG Islands; D019281:Dimerization; D005260:Female; D007111:Immunity, Cellular; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood / Q000276:immunology; D007273:Injections, Intramuscular; D007371:Interferon-gamma / Q000096:biosynthesis / Q000097:blood; D018664:Interleukin-12 / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D015848:Interleukin-5 / Q000096:biosynthesis / Q000097:blood; D007694:Killer Cells, Natural / Q000276:immunology; D008168:Lung / Q000821:virology; D008745:Methylation; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D011024:Pneumonia, Viral / Q000276:immunology / Q000473:pathology / Q000517:prevention & control* / Q000821:virology; D021122:Protein Subunits; D011657:Pulmonary Eosinophilia / Q000276:immunology / Q000473:pathology / Q000517:prevention & control / Q000821:virology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology / Q000473:pathology / Q000517:prevention & control* / Q000821:virology; D022261:Respiratory Syncytial Virus Vaccines / Q000008:administration & dosage / Q000276:immunology*; D012136:Respiratory Syncytial Viruses / Q000276:immunology* / Q000302:isolation & purification; D013154:Spleen / Q000276:immunology; D014611:Vaccination / Q000379:methods*; D014764:Viral Proteins / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D007074:Immunoglobulin G; D015848:Interleukin-5; D021122:Protein Subunits; D022261:Respiratory Syncytial Virus Vaccines; D014764:Viral Proteins; D018664:Interleukin-12; D007371:Interferon-gamma