title: Neonatal administration of IL-12 enhances the protective efficacy of antiviral vaccines.
abstract: Neonates are highly susceptible to infectious agents and are known to display polarized expression of Th2-like cytokines and Abs. This neonatal immune bias has important implications for the development of vaccine strategies, particularly against viral infections. We now report that coadministration of IL-12 and an influenza subunit vaccine at birth enhances the protective efficacy of antiviral vaccination. Immunization and treatment with IL-12 within 24 h of birth resulted in elevated expression of IFN-gamma, IL-10, and IL-15 mRNA in the spleens of newborn mice compared with animals exposed to vaccine only. In addition, these animals showed dramatic increases in IFN-gamma-, IL-2-, and IL-4-secreting cells, and in IgG2a Ab levels upon adult challenge compared with mice primed with vaccine alone. Most importantly, animals vaccinated and simultaneously treated with IL-12 at birth displayed enhanced survival after lethal challenge with infectious influenza virus as adults compared with infected animals that had been primed with vaccine alone. This augmented protection required B cells and could be transferred to naive mice by immune serum. Collectively, these results provide evidence that administration of IL-12 to neonates induces a Th1-like response in newborns and elicits protective antiviral immune memory.
authors.affiliation: Center for Immunology and Microbial Disease, Albany Medical College, Albany, NY 12208, USA.
authors.forename: B P
authors.initials: BP
authors.lastname: Arulanandam
authors.forename: J N
authors.initials: JN
authors.lastname: Mittler
authors.forename: W T
authors.initials: WT
authors.lastname: Lee
authors.forename: M
authors.initials: M
authors.lastname: O'Toole
authors.forename: D W
authors.initials: DW
authors.lastname: Metzger
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D000831:Animals, Newborn / Q000235:genetics / Q000254:growth & development / Q000276:immunology*; D000914:Antibodies, Viral / Q000096:biosynthesis / Q000097:blood / Q000502:physiology; D016207:Cytokines / Q000096:biosynthesis; D004359:Drug Therapy, Combination; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis / Q000097:blood / Q000502:physiology; D007156:Immunologic Memory; D009980:Influenza A virus / Q000276:immunology; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology* / Q000627:therapeutic use*; D007274:Injections, Intraperitoneal; D018664:Interleukin-12 / Q000008:administration & dosage*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009976:Orthomyxoviridae Infections / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D016207:Cytokines; D007132:Immunoglobulin Isotypes; D007252:Influenza Vaccines; D018664:Interleukin-12