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. 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-gamma 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.
van der Meide
Peter H
PH
Cytokine Biology Unit, Central Laboratory Animal Institute, Utrecht University, Utrecht, The Netherlands. p.h.vandermeide@gdl.uu.nl
Villinger
Francois
F
Ansari
Aftab A
AA
Groenestein
Reno J
RJ
de Labie
Miranda C D C
MC
van den Hout
Yvon J M
YJ
Koornstra
Wim H
WH
Bogers
Willy M J M
WM
Heeney
Jonathan L
JL
D000818:Animals; D000917:Antibody Formation; D016466:CHO Cells; D006224:Cricetinae; D015483:HIV Antibodies / Q000096:biosynthesis* / Q000097:blood / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000096:biosynthesis*; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology*; D018793:Interleukin-13 / Q000096:biosynthesis*; D007376:Interleukin-2 / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000096:biosynthesis*; D008253:Macaca mulatta; D008297:Male
D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D018793:Interleukin-13; D007376:Interleukin-2; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma