The immunogenicity of subunit vaccines for respiratory syncytial virus after co-formulation with aluminum hydroxide adjuvant and recombinant interleukin-12.
The effects of recombinant interleukin-12 (rIL-12) on immune responses generated by subunit vaccines for respiratory syncytial virus (RSV) were evaluated in BALB/c mice. Parenteral co-administration of rIL-12 with F/AlOH or F/PBS resulted in accelerated clearance of infectious virus from the lungs 4 days after challenge. The immune responses elicited by 0.03 microg of F protein plus 10 ng of rIL-12 adsorbed to AlOH were more efficacious than those induced by 3 microg of F protein co-formulated with 1,000 ng of rIL-12 in PBS alone. Adsorption to AIOH prolonged the presence of rIL-12 in the sera. The resultant systemic humoral immune responses after vaccination with F/AlOH or G/AlOH were dependent on the dose of rIL-12 and characterized by heightened serum immunoglobulin G2a (IgG2a) antibody titers. Co-administration of rIL-12 with F/AlOH was also associated with diminished protein-specific IgE titers, elevated neutralizing antibody titers, and interferon-gamma and (IFN-gamma) in the sera, and enhanced antigen-dependent killer cell activity in the lungs after challenge. For maximum benefit, the data suggested that rIL-12 must be co-administered with F/AlOH. Collectively, the results indicated that rIL-12 directed immune responses toward a type 1 phenotype. However, examination of pulmonary inflammatory cells after challenge suggested that the type 1 phenotype was not absolute. Co-formulation with rIL-12 did not diminish pulmonary eosinophilia upon challenge of naive mice primed with F/AlOH, G/AlOH, or FI-RSV, and CD4+ T cells were expanded relative to the CD8+ T-cell compartment. These results are important for the future design of subunit vaccines against RSV.
Hancock
G E
GE
Department of Immunology Research, Wyeth-Lederle Vaccines, West Henrietta, NY 14586-9728, USA. hancocg@war.wyeth.com
Smith
J D
JD
Heers
K M
KM
D000276:Adjuvants, Immunologic; D000536:Aluminum Hydroxide; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D005260:Female; D015707:HN Protein; D007111:Immunity, Cellular; D007114:Immunization; D007371:Interferon-gamma / Q000097:blood; D018664:Interleukin-12 / Q000008:administration & dosage / Q000097:blood / Q000235:genetics / Q000276:immunology*; D015848:Interleukin-5 / Q000276:immunology; D008168:Lung / Q000166:cytology / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000276:immunology; D018357:Respiratory Syncytial Virus Infections / Q000517:prevention & control* / Q000821:virology; D012136:Respiratory Syncytial Viruses / Q000276:immunology*; D014759:Viral Envelope Proteins; D014764:Viral Proteins / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D015707:HN Protein; D015848:Interleukin-5; D011994:Recombinant Proteins; D014759:Viral Envelope Proteins; D014764:Viral Proteins; D014765:Viral Vaccines; C116204:attachment protein G; D018664:Interleukin-12; D000536:Aluminum Hydroxide; D007371:Interferon-gamma