CpG containing oligodeoxynucleotides are potent adjuvants for parenteral vaccination with the fusion (F) protein of respiratory syncytial virus (RSV).
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.
Hancock
G E
GE
Department of Immunology Research, Wyeth-Lederle Vaccines, 211 Bailey Road, West Henrietta, NY 14586, USA. hancocg@war.wyeth.com
Heers
K M
KM
Smith
J D
JD
Scheuer
C A
CA
Ibraghimov
A R
AR
Pryharski
K S
KS
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*
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