Adsorption to aluminum hydroxide promotes the activity of IL-12 as an adjuvant for antibody as well as type 1 cytokine responses to HIV-1 gp120.
A series of protocols were tested to examine the adjuvant effects of IL-12 on humoral and type 1 cytokine responses elicited in mice by recombinant gp120 envelope protein from HIV-1. This Ag fails to induce detectable Ab responses when administered s.c. alone, but stimulates low Ab levels when combined with aluminum hydroxide (alum). Moreover, when i.p. injected rIL-12 was included in the immunization, no increase in Ab production was observed. Importantly, optimal gp120 Ab responses were achieved by immunizing mice s.c. with gp120 and rIL-12 simultaneously coadsorbed to alum. These animals displayed a highly polarized, type 1 cytokine profile, with the emergence of anti-gp120 Ig belonging to the IgG2 and IgG3 isotypes. In addition, a major increase occurred in Ab of the IgG1 subclass. The superior adjuvant activity of alum-adsorbed IL-12 compared with that of the free cytokine correlated with the prolonged detection of IFN-gamma in the sera of animals immunized using the former procedure. In related experiments, in vitro neutralization of IL-12 was shown to inhibit IFN-gamma production by spleen cells from mice immunized with gp120 plus alum, but not by splenocytes from mice primed in the presence of IL-12, suggesting that the latter protocol induces a stable type 1 phenotype. These studies demonstrate that presentation of IL-12 on alum enhances its immunomodulatory effects and establish a protocol for the use of the cytokine as an adjuvant for simultaneously promoting both humoral Ab and type 1 cytokine responses.
Jankovic
D
D
Laboratory of Parasitic Diseases, Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Caspar
P
P
Zweig
M
M
Garcia-Moll
M
M
Showalter
S D
SD
Vogel
F R
FR
Sher
A
A
D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000327:Adsorption; D000536:Aluminum Hydroxide / Q000008:administration & dosage*; D000818:Animals; D005069:Evaluation Studies as Topic; D005260:Female; D015483:HIV Antibodies / Q000096:biosynthesis* / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D007111:Immunity, Cellular; D007074:Immunoglobulin G / Q000096:biosynthesis* / Q000276:immunology; D007279:Injections, Subcutaneous; D007371:Interferon-gamma / Q000378:metabolism*; D018664:Interleukin-12 / Q000008:administration & dosage* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D014677:Pharmaceutical Vehicles; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology; D018417:Th1 Cells / Q000378:metabolism*; D014611:Vaccination
D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D007074:Immunoglobulin G; D014677:Pharmaceutical Vehicles; D011994:Recombinant Proteins; D018664:Interleukin-12; D000536:Aluminum Hydroxide; D007371:Interferon-gamma