Intranasal interleukin-12 is a powerful adjuvant for protective mucosal immunity.
The use of interleukin (IL)-12 as a new vaccine adjuvant for stimulating protective antiviral mucosal immunity has been examined. Mice were immunized intranasally (in) with an influenza vaccine consisting of soluble hemagglutinin (H1) and neuraminidase (N1) plus IL-12. This treatment resulted in elevated levels of lung and splenic interferon-gamma and IL-10 mRNA. Total and IgG2a anti-H1N1 antibody levels in serum were significantly elevated, as were total, IgG1, IgG2a, and secretory IgA antibody levels in bronchoalveolar lavage (BAL) fluids compared with animals receiving vaccine alone. Mice immunized in with vaccine and IL-12 also exhibited decreased weight loss and dramatically enhanced survival after lethal challenge with infectious influenza virus. Protection was dependent upon the presence of B cells and could be transferred to naive mice by inoculation of either serum or BAL fluid from IL-12-treated mice. These findings show for the first time that soluble IL-12 delivered in serves as a powerful respiratory adjuvant for protective antiviral immunity.
Arulanandam
B P
BP
Center for Immunology, Albany Medical College, Albany, NY 12208, USA. arulanb@mail.amc.edu
O'Toole
M
M
Metzger
D W
DW
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood*; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology*; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000008:administration & dosage / Q000276:immunology; D018928:Immunity, Mucosal / Q000187:drug effects*; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood / Q000145:classification; D007075:Immunoglobulin M / Q000172:deficiency; D007252:Influenza Vaccines / Q000008:administration & dosage*; D007371:Interferon-gamma / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics; D018664:Interleukin-12 / Q000008:administration & dosage / Q000494:pharmacology*; D008168:Lung / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009439:Neuraminidase / Q000008:administration & dosage / Q000276:immunology; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000517:prevention & control; D012333:RNA, Messenger / Q000235:genetics; D013154:Spleen / Q000276:immunology; D013997:Time Factors
D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007252:Influenza Vaccines; D012333:RNA, Messenger; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma; D009439:Neuraminidase