Glucopyranosyl lipid A adjuvant significantly enhances HIV specific T and B cell responses elicited by a DNA-MVA-protein vaccine regimen.
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.
Imperial College London, Department of Infectious Diseases, Division of Medicine, Norfolk Place, London, United Kingdom.
Paul F
PF
McKay
Imperial College London, Department of Infectious Diseases, Division of Medicine, Norfolk Place, London, United Kingdom.
Alethea V
AV
Cope
Imperial College London, Department of Infectious Diseases, Division of Medicine, Norfolk Place, London, United Kingdom.
Jamie F S
JF
Mann
MRC Clinical Trials Unit, London, United Kingdom.
Sarah
S
Joseph
Centro Nacional de Biotecnología, CSIC, Department of Molecular and Cellular Biology, Campus Universidad Autónoma, Madrid, Spain.
Mariano
M
Esteban
Imperial College London, Department of Infectious Diseases, Division of Medicine, Norfolk Place, London, United Kingdom.
Roger
R
Tatoud
Infectious Disease Research Institute, Seattle, Washington, United States of America.
Darrick
D
Carter
Infectious Disease Research Institute, Seattle, Washington, United States of America.
Steven G
SG
Reed
Imperial College London, Department of Infectious Diseases, Division of Medicine, Norfolk Place, London, United Kingdom.
Jonathan
J
Weber
Imperial College London, Department of Infectious Diseases, Division of Medicine, Norfolk Place, London, United Kingdom.
Robin J
RJ
Shattock
D016915:AIDS Vaccines / Q000008:administration & dosage; D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D001402:B-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D005260:Female; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control*; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D008050:Lipid A / Q000008:administration & dosage / Q000031:analogs & derivatives*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids / Q000008:administration & dosage; D011817:Rabbits; D013154:Spleen / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology*; D014611:Vaccination; D064166:Vaccine Potency; D019444:Vaccines, DNA / Q000008:administration & dosage; D014765:Viral Vaccines / Q000008:administration & dosage; D054299:env Gene Products, Human Immunodeficiency Virus / Q000276:immunology
D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D016207:Cytokines; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D008050:Lipid A; C560489:MVA vaccine; D019444:Vaccines, DNA; D014765:Viral Vaccines; D054299:env Gene Products, Human Immunodeficiency Virus; C097729:gp140 envelope protein, Human immunodeficiency virus 1