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 language | English |
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Pages (from-to) | e84707 |
Journal | PLoS ONE |
Volume | 9 |
Issue number | 1 |
DOIs | |
Publication status | Published - 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