Induction of high-titer neutralizing antibodies, using hybrid human immunodeficiency virus V3-Ty viruslike particles in a clinically relevant adjuvant

Abstract

The localization of neutralization determinants within the envelope glycoproteins of human immunodeficiency virus (HIV) has been largely achieved by immunizing small animals in conjunction with Freund's adjuvant. However, for eventual use in humans, candidate HIV vaccine components must also be efficacious in a nontoxic formulation. We describe here the production of hybrid Ty viruslike particles carrying the major neutralizing domain of HIV and demonstrate the induction of high-titer virus-neutralizing antibodies and an HIV-specific T-cell proliferative response after immunization in conjunction with aluminum hydroxide. As aluminum hydroxide and aluminum phosphate are the only adjuvants currently licensed for use in humans, these observations have implications for the development of an effective vaccine against HIV.

Enhanced activation of human T cell clones specific for virus-like particles expressing the HIV V3 loop in the presence of HIV V3 loop-specific polyclonal antibodies

“…Non-hybrid VLP and hybrid VLP containing the V3 loop region from the clone MN (V3-VLP) were constructed and purified as previously described [33][34][35][36]. A TYA:V3 fusion gene was constructed by inserting synthetic oligonucleotides encoding the HIV-1 MN V3 sequence NCTRPNNNTRKRIR-IQRGPGRAFVTIGKIGNMRQAHCNIS into a yeast expression vector (pOGS40) that contains a truncated TYA gene encoding amino acids 1-381 of protein pi.…”

“…[17,18], help can be provided by T cells specific for helper epitopes on gpl20 [20,21], but this may not be an cPTective approach, since T helper cells specific for gpl 20 [22][23][24][25][26] are (i) at low frequency in the naive repertoire [27], and (ii) specific for T epitopes that may differ among strains [28,29], Therefore alternative carrier antigens should be tested [30], Among the various options available, particulate proteinaceous carriers have been found to be effective in vaccine delivery [31,32]. One such system, utilizing yeast-derived recombinant Ty: viruslike particles (Ty-VLP), has been shown to be an effective antigen-presentation system for a variety of antigenic sequences [33], Recently, Ty-VLP carrying the V3 loop of HIV gpl20 (V3-VLP) have been shown to induce V3-specific antibody responses in rabbits [34] and V3-specific T helper cell responses and cytotoxic T lymphocyte responses in mice [31,32]. In this study we demonstrate in vitro that the human repertoire includes T cells capable of recognizing the carrier VLP protein, pi, and that antibodies specific for V3 potentiate presentation to and activation of VLP-specific T cells.…”

Ability of yeast Ty-VLPs (virus-like particles) containing varicella-zoster virus (VZV)gE and assembly protein fragments to induce in vitro proliferation of human lymphocytes from VZV immune patients

“…A potential VZV vaccine strategy has been devised using hybrid yeast Ty-virus like particles (VLPs) containing VZV gE (amino acids 1-134, 101-161, or 161-233) and assembly protein (AP) inserts as a polyvalent particulate antigen delivery system. VLPs containing viral protein inserts have been shown to be potent immunogens, eliciting both B-and T-lymphocyte (CD4 + and CD8 + ) responses [Griffiths et al, 1991;Harris et al, 1992Layton et al, 1993;Martin et al, 1993;Gilbert et al, 1997].…”

Cloning, expression, and immunogenicity of the assembly protein of varicella‐zoster virus and detection of the products of open reading frame 33

“…Overexpression of hybrid TYA:antigen genes in yeast results in the production of p1 fusion protein, which assembles into virus-like particles (VLPs). VLPs carrying viral proteins are potent inducers of humoral and cellular antiviral responses [Griffiths et al, 1991;Harris et al, 1992;Martin et al, 1993].…”