Primate immune responses to HIV-1 Env formulated in the saponin-based adjuvant AbISCO-100 in the presence or absence of TLR9 co-stimulation.

Abstract

Protein-based vaccines require adjuvants to achieve optimal responses. Toll-like receptor (TLR) 9 agonists were previously shown to improve responses to protein-based vaccines, such as the Hepatitis B virus vaccine formulated in alum. Here, we used CpG-C together with the clinically relevant saponin-based adjuvant AbISCO-100/Matrix-M (AbISCO), to assess if TLR9 co-stimulation would quantitatively or qualitatively modulate HIV-1 envelope glycoprotein (Env)-specific B and T cell responses in rhesus macaques. The macaques were inoculated with soluble Env trimers in AbISCO, with or without the addition of CpG-C, using an interval similar to the Hepatitis B virus vaccine. Following a comprehensive evaluation of antigen-specific responses in multiple immune compartments, we show that the Env-specific circulating IgG, memory B cells and plasma cells displayed similar kinetics and magnitude in the presence or absence of CpG-C and that there was no apparent difference between the two groups in the elicited HIV-1 neutralizing antibody titers or antigen-specific CD4+ T cell responses. Importantly, the control of SHIV viremia was significantly improved in animals from both Env-immunized groups relative to adjuvant alone controls, demonstrating the potential of AbISCO to act as a stand-alone adjuvant for Env-based vaccines.

• Authors: Paola Martinez, Christopher Sundling, Sijy O'Dell, John R Mascola, Richard T Wyatt, Gunilla B Karlsson Hedestam
• Journal: Scientific reports (Sci Rep) Vol. 5 Pg. 8925 (Mar 12 2015) ISSN: 2045-2322 [Electronic] England
• PMID: 25762407 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)

Chemical References

• Adjuvants, Immunologic
• Antibodies, Neutralizing
• CpG ODN 2395
• Cytokines
• HIV Antibodies
• Immunoglobulin G
• Oligodeoxyribonucleotides
• Saponins
• Toll-Like Receptor 9
• env Gene Products, Human Immunodeficiency Virus

Topics

• Adjuvants, Immunologic
• Animals
• Antibodies, Neutralizing (immunology)
• Antibody Specificity
• B-Lymphocytes (immunology, metabolism)
• Cytokines (metabolism)
• Disease Models, Animal
• HIV Antibodies (immunology)
• HIV Infections (immunology, metabolism)
• HIV-1 (immunology)
• Humans
• Immunity, Mucosal
• Immunization
• Immunoglobulin G (immunology)
• Immunologic Memory
• Macaca mulatta
• Oligodeoxyribonucleotides (administration & dosage)
• Plasma Cells (immunology, metabolism)
• Primates
• Saponins (administration & dosage)
• Simian Immunodeficiency Virus (immunology)
• T-Lymphocyte Subsets (immunology, metabolism)
• Toll-Like Receptor 9 (agonists, metabolism)
• env Gene Products, Human Immunodeficiency Virus (immunology)