The Control of the Antibody Isotype Response to Recombinant Human Immunodeficiency Virus gp120 Antigen by Adjuvants

Abstract

Both saponin and muramyl dipeptide (MDP) formulated with a squalane-in-water emulsion of large particle size prepared with a vortex mixer were superior to Al(OH)3 as adjuvants for HIV gp120 in mice. All the adjuvants induced IgG1 antibody, but saponin elicited the highest titers of IgG2a. The secretion of interleukin-5 (IL-5) and interferon gamma (IFN gamma) by lymph node cells cultured in vitro with gp120 was studied. All the cultures secreted IL-5, but only those from saponin-immunized mice produced IFN gamma, suggesting that saponin is capable of activating both the Th1 and TH2 T-cell subsets. The titers of neutralizing antibodies were low with both MDP and saponin, and they occurred in mice which were also positive for antibodies against a V3 loop peptide. Glucosaminylmuramyl dipeptide (GMDP) which is less pyrogenic than MDP and a nonpyrogenic analog GMDPA, displayed equivalent adjuvant activity to MDP. The level and isotype composition of antibodies induced by GMDP in combination with squalane emulsions depended on the dimension of the emulsion particles. With a large (2500 nm) particle size the response was confined to IgG1 in Balb/c mice, but when this was reduced to 150 nm by sonication the antibody response was increased and relatively high levels of IgG2a appeared in some mice.

Immunogenicity of HIV-1LAI gp160 and env peptides in squirrel monkey Saimiri sciureus using alumine and experimental adjuvants

“…These data, obtained in Saimiri monkeys, are in accordance with those obtained either in mice or in primates other than neoprimates [26,27]. Importantly, in the design of a future HIV-1 vaccine, synthetic peptides might be highly efficient immunogens [16,23,25,28,29].…”

Saponin adjuvant primes for a dominant interleukin‐10 production to ovalbumin and to Trypanosoma cruzi antigen

“…4 The antibody isotypes stimulated in the mouse by saponins as adjuvants are immunoglobulin (Ig)G1 [5][6][7][8] associated with IgG2b 6,7 and/or with IgG2a 4,5,7,8 depending on the antigen and protocols used for immunization. The pattern of induced antibody isotypes allied to the enhanced secretion of interferon-g (IFN-g) and interleukin-2 (IL-2) 6 or of IFN-g and interleukin-5 (IL-5) 5 is considered consistent with the stimulation of both T helper (Th)1 and Th2-type cytokine responses by immunization protocols that use saponin as adjuvant. Among a panel of different adjuvants that included muramyl dipeptide, alum, Freund's incomplete adjuvant, Corynebacterium parvum and squalane, saponin was the only one to induce delayed-type hypersensitivity (DTH) to a purified glycoprotein from the protozoa Trypanosoma cruzi and partial protective immunity to a challenge with live parasites.…”

“…E. Tadokoro et al However, saponins also induced significant levels of IgG2a and IgG2b as well as IgG1 antibodies in other immunization protocols. [4][5][6][7] Saponin adjuvants are also potent inducers of anti-OA CD8…”

“…However, by comparison with muramyl dipeptide and Al(OH) 3 only Quil A was effective at stimulating high IFN-g production to the HIV glycoprotein 120 (gp 120). 5 In addition, complexes comprising Quil A, lipids and influenza virus antigen were efficient inducers of Th1-type cytokine responses. 30 Quil A saponin also augmented antibody responses to T-independent antigens.…”

A Novel, Recombinant Triple Antigen Hepatitis B Vaccine (Hepacare^®)

“…The type of response elicited was also balanced, inducing both Th1 and Th2 type IgG responses and strong T cell prolifera-tion and cytokine release in vitro. This mixed response probably results from the adjuvant's contribution primarily as a Th2-type response inducer [57] and the particulate nature of Hepacare contributing a Th1 bias [58].…”