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

• Published in: The Journal of immunology (1950) Vol. 159; no. 5; pp. 2409 - 2417
• Main Authors: Jankovic, D, Caspar, P, Zweig, M, Garcia-Moll, M, Showalter, SD, Vogel, FR, Sher, A
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01.09.1997
• Subjects: Adjuvants, Immunologic - administration & dosage; Adsorption; AIDS Vaccines - administration & dosage; AIDS Vaccines - immunology; AIDS/HIV; Aluminum Hydroxide - administration & dosage; Animals; Evaluation Studies as Topic; Female; HIV Antibodies - biosynthesis; HIV Antibodies - immunology; HIV Envelope Protein gp120 - immunology; HIV-1 - immunology; human immunodeficiency virus 1; Immunity, Cellular; Immunoglobulin G - biosynthesis; Immunoglobulin G - immunology; Injections, Subcutaneous; Interferon-gamma - secretion; Interleukin-12 - administration & dosage; Interleukin-12 - immunology; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Pharmaceutical Vehicles; Recombinant Proteins - administration & dosage; Recombinant Proteins - immunology; Th1 Cells - secretion; Vaccination
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.159.5.2409

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.