The adjuvant AlhydroGel elicits higher antibody titres than AddaVax when combined with HIV-1 subtype C gp140 from CAP256.

Abstract

With the HIV-1 epidemic in southern Africa still rising, a prophylactic vaccine against the region's most prolific subtype (subtype C) would be a significant step forward. In this paper we report on the effect of 2 different adjuvants, AddaVax and AlhydroGel, formulated with HIV-1 subtype C gp140, on the development of binding and neutralising antibody titres in rabbits. AddaVax is a squalene-based oil-in-water nano-emulsion (similar to MF59) which can enhance both cellular and humoral immune responses, whilst AlhydroGel (aluminium hydroxide gel) mainly drives a Th2 response. The gp140 gene tested was derived from the superinfecting virus (SU) from participant CAP256 in the CAPRISA 002 Acute infection cohort. The furin cleavage site of the Env protein was replaced with a flexible linker and an I559P mutation introduced. Lectin affinity purified soluble Env protein was mainly trimeric as judged by molecular weight using BN-PAGE and contained intact broadly neutralising epitopes for the V3-glycan supersite (monoclonal antibodies PGT128 and PGT135), the CD4 binding site (VRC01) and the V2-glycan (PG9) but not for the trimer-specific monoclonal antibodies PG16, PGT145 and CAP256-VRC26_08. When this soluble Env protein was tested in rabbits, AlhydroGel significantly enhanced soluble Env and V1V2 binding antibodies when compared to AddaVax. Finally, AlhydroGel resulted in significantly higher neutralization titres for a subtype C Tier 1A virus (MW965.26) and increased neutralization breadth to Tier 1A and 1B viruses. However, no autologous Tier 2 neutralisation was observed. These data suggest that adjuvant selection is critical for developing a successful vaccine and AlhydroGel should be further investigated. Additional purification of trimeric native-like CAP256 Env and/or priming with DNA or MVA might enhance the induction of neutralizing antibodies and possible Tier 2 HIV-1 neutralisation.

• Authors: Michiel T van Diepen, Rosamund Chapman, Penny L Moore, Emmanuel Margolin, Tandile Hermanus, Lynn Morris, Phindile Ximba, Edward P Rybicki, Anna-Lise Williamson
• Journal: PloS one (PLoS One) Vol. 13 Issue 12 Pg. e0208310 ( 2018) ISSN: 1932-6203 [Electronic] United States
• PMID: 30557314 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• AIDS Vaccines
• Addavax
• Adjuvants, Immunologic
• Antibodies, Neutralizing
• HIV Antibodies
• Polysorbates
• env Gene Products, Human Immunodeficiency Virus
• gp140 envelope protein, Human immunodeficiency virus 1
• Squalene

Topics

• AIDS Vaccines (immunology)
• Adjuvants, Immunologic (pharmacology)
• Antibodies, Neutralizing (metabolism)
• HEK293 Cells
• HIV Antibodies (blood, metabolism)
• HIV-1 (metabolism)
• Humans
• Immunization
• Polysorbates (pharmacology)
• Squalene (pharmacology)
• env Gene Products, Human Immunodeficiency Virus (metabolism)