Stimulation of both humoral and cellular immune responses to HIV-1 gp120 by interleukin-12 in Rhesus macaques

The adjuvant effect of recombinant Rhesus macaque interleukin-12 (RhIL-12) on the induction of cellular and humoral immune responses elicited by the HIV-1 subunit vaccine protein gp120 in Rhesus macaques was examined. RhIL-12 in conjunction with gp120 was given at day 0, 28 and 84 intramuscularly. C...

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Published in:	Vaccine Vol. 20; no. 17; pp. 2296 - 2302
Main Authors:	van der Meide, Peter H., Villinger, Francois, Ansari, Aftab A., Groenestein, Reno J., de Labie, Miranda C.D.C., van den Hout, Yvon J.M., Koornstra, Wim H., Bogers, Willy M.J.M., Heeney, Jonathan L.
Format:	Journal Article
Language:	English
Published:	Oxford Elsevier Ltd 22-05-2002 Elsevier
Subjects:	Animals Antibody Formation Biological and medical sciences CHO Cells Cricetinae Fundamental and applied biological sciences. Psychology HIV HIV Antibodies - biosynthesis HIV Antibodies - blood HIV Antibodies - immunology HIV Envelope Protein gp120 - genetics HIV Envelope Protein gp120 - immunology HIV-1 - immunology Human viral diseases Humans Immunity, Cellular Infectious diseases Interferon-gamma - biosynthesis Interleukin-12 Interleukin-12 - genetics Interleukin-12 - immunology Interleukin-13 - biosynthesis Interleukin-2 - biosynthesis Interleukin-4 - biosynthesis Macaca mulatta Macaques Male Medical sciences Microbiology Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies Viral diseases Viral diseases of the lymphoid tissue and the blood. Aids Virology SIV, simian immunodeficiency virus HIV HIV, human immunodeficiency virus IL, interleukin SFC, spot forming cells Interleukin-12 Macaques SHIV, simian-human immunodeficiency virus ELISPOT, enzyme-linked immunospot pc, producing cells Immune response HIV-1 virus Toxicity Cytokine Retroviridae Interleukin 12 Cellular immunity Macaca mulatta Vaccine Lentivirus Virus Vertebrata Mammalia Immunological adjuvant Primates Simioidea Human immunodeficiency virus Humoral immunity
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Summary:	The adjuvant effect of recombinant Rhesus macaque interleukin-12 (RhIL-12) on the induction of cellular and humoral immune responses elicited by the HIV-1 subunit vaccine protein gp120 in Rhesus macaques was examined. RhIL-12 in conjunction with gp120 was given at day 0, 28 and 84 intramuscularly. Coadministration resulted in an approximate 10-fold increase in plasma anti-gp120 antibody levels as compared to levels generated in control monkeys receiving gp120 alone. Potentiation of the humoral arm of the immune response was evident by both ELISA and an antiviral bioassay. In addition, RhIL-12 was found to produce a significant increase in gp120-specific proliferative responses and in the frequency of antigen-specific IFN-γ and IL-2 producing T cells after restimulation of PBMC with gp120 in vitro indicating that RhIL-12 potentiates cell-mediated immune responses as well. A critical finding was that during the course of the study, RhIL-12 did not induce a neutralizing antibody response to the administered cytokine. The doses of RhIL-12 were well tolerated and no detectable adverse side-effects on hematopoietic and hepatic parameters were noted. The data revealed that IL-12, when coadministered intramuscularly, acts as a potent adjuvant which is able to enhance not only cellular but also humoral immune responses to gp120 in non-human primates and may have to be considered in future HIV vaccine strategies.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2
ISSN:	0264-410X 1873-2518
DOI:	10.1016/S0264-410X(02)00101-9