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 gene rated by subunit vaccines for respiratory syncytial virus (RSV) were evalua ted 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 mu g of F prot ein plus 10 ng of rIL-12 adsorbed to AlOH were more efficacious than those induced by 3 mu g of F protein co-formulated with 1,000 ng of rIL-12 in PBS alone. Adsorption to AlOH prolonged the presence of rIL-12 in the sera. Th e resultant systemic humoral immune responses after vaccination with F/AlOH or G/AlOH were dependent on the dose of rIL-12 and characterized by height ened serum immunoglobulin G(2a) (IgG(2a)) antibody titers. Go-administratio n of rIL-12 with F/AlOH was also associated with diminished protein-specifi c IgE titers, elevated neutralizing antibody titers, and interferon-gamma a nd (IFN-gamma) in the sera, and enhanced antigen-dependent killer cell acti vity 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 sugges ted that the type 1 phenotype was not absolute. Go-formulation with rIL-12 did not diminish pulmonary eosinophilia upon challenge of naive mice primed with F/AIOH, G/AlOH, or FI-RSV, and CD4(+) T cells were expanded relative to the CD8(+) T-cell compartment. These results are important for the futur e design of subunit vaccines against RSV.