Glucopyranosyl lipid A adjuvant significantly enhances HIV specific T and B cell responses elicited by a DNA-MVA-protein vaccine regimen

Paul F McKay, Alethea V Cope, Jamie F S Mann, Sarah Joseph, Mariano Esteban, Roger Tatoud, Darrick Carter, Steven G Reed, Jonathan Weber, Robin J Shattock

Research output: Contribution to journalArticle (Academic Journal)peer-review

Abstract

Using a unique vaccine antigen matched and single HIV Clade C approach we have assessed the immunogenicity of a DNA-poxvirus-protein strategy in mice and rabbits, administering MVA and protein immunizations either sequentially or simultaneously and in the presence of a novel TLR4 adjuvant, GLA-AF. Mice were vaccinated with combinations of HIV env/gag-pol-nef plasmid DNA followed by MVA-C (HIV env/gag-pol-nef) with HIV CN54gp140 protein (+/-GLA-AF adjuvant) and either co-administered in different muscles of the same animal with MVA-C or given sequentially at 3-week intervals. The DNA prime established a population of B cells that were able to mount a statistically significant anamnestic response to the boost vaccines. The greatest antigen-specific antibody response was observed in animals that received all vaccine components. Moreover, a high proportion of the total mucosal IgG (20 - 50%) present in the vaginal vault of these vaccinated animals was vaccine antigen-specific. The potent elicitation of antigen-specific immune responses to this vaccine modality was also confirmed in rabbits. Importantly, co-administration of MVA-C with the GLA-AF adjuvanted HIV CN54gp140 protein significantly augmented the antigen-specific T cell responses to the Gag antigen, a transgene product expressed by the MVA-C vector in a separate quadriceps muscle. We have demonstrated that co-administration of MVA and GLA-AF adjuvanted HIV CN54gp140 protein was equally effective in the generation of humoral responses as a sequential vaccination modality thus shortening and simplifying the immunization schedule. In addition, a significant further benefit of the condensed vaccination regime was that T cell responses to proteins expressed by the MVA-C were potently enhanced, an effect that was likely due to enhanced immunostimulation in the presence of systemic GLA-AF.

Original languageEnglish
Pages (from-to)e84707
JournalPLoS ONE
Volume9
Issue number1
DOIs
Publication statusPublished - 2014

Keywords

  • AIDS Vaccines/administration & dosage
  • Adjuvants, Immunologic/administration & dosage
  • Animals
  • Antibodies, Viral/blood
  • B-Lymphocytes/immunology
  • Cells, Cultured
  • Cytokines/metabolism
  • Female
  • HIV Infections/immunology
  • Humans
  • Immunoglobulin A/blood
  • Immunoglobulin G/blood
  • Lipid A/administration & dosage
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Plasmids/administration & dosage
  • Rabbits
  • Spleen/immunology
  • T-Lymphocytes/immunology
  • Vaccination
  • Vaccine Potency
  • Vaccines, DNA/administration & dosage
  • Viral Vaccines/administration & dosage
  • env Gene Products, Human Immunodeficiency Virus/immunology

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