Control of heterologous simian immunodeficiency virus SIVsmE660 infection by DNA and protein coimmunization regimens combined with different Toll-like-receptor-4-based adjuvants in macaques
Por:
Singh S., Ramírez-Salazar E.G., Doueiri R., Valentin A., Rosati M., Hu X., Keele B.F., Shen X., Tomaras G.D., Ferrari G., LaBranche C., Montefiori D.C., Das J., Alter G., Trinh H.V., Hamlin C., Rao M., Dayton F., Bear J., Chowdhury B., Alicea C., Lifson J.D., Broderick K.E., Sardesai N.Y., Sivananthan S.J., Fox C.B., Reed S.G., Venzon D.J., Hirsch V.M., Pavlakis G.N., Felber B.K.
Publicada:
1 ene 2018
Resumen:
We developed a method of simultaneous vaccination with DNA and protein resulting in robust and durable cellular and humoral immune responses with efficient dissemination to mucosal sites and protection against simian immunodeficiency virus (SIV) infection. To further optimize the DNA-protein coimmunization regimen, we tested a SIVmac251-based vaccine formulated with either of two Toll-like receptor 4 (TLR4) ligand-based liposomal adjuvant formulations (TLR4 plus TLR7 [TLR4+7] or TLR4 plus QS21 [TLR4+QS21]) in macaques. Although both vaccines induced humoral responses of similar magnitudes, they differed in their functional quality, including broader neutralizing activity and effector functions in the TLR4+7 group. Upon repeated heterologous SIVsmE660 challenge, a trend of delayed viral acquisition was found in vaccinees compared to controls, which reached statistical significance in animals with the TRIM-5a-resistant (TRIM-5a R) allele. Vaccinees were preferentially infected by an SIVsmE660 transmitted/founder virus carrying neutralizationresistant A/K mutations at residues 45 and 47 in Env, demonstrating a strong vaccine- induced sieve effect. In addition, the delay in virus acquisition directly correlated with SIVsmE660-specific neutralizing antibodies. The presence of mucosal V1V2 IgG binding antibodies correlated with a significantly decreased risk of virus acquisition in both TRIM-5a R and TRIM-5a-moderate/sensitive (TRIM-5a M/S) animals, although this vaccine effect was more prominent in animals with the TRIM-5a R allele. These data support the combined contribution of immune responses and genetic background to vaccine efficacy. Humoral responses targeting V2 and SIV-specific T cell responses correlated with viremia control. In conclusion, the combination of DNA and gp120 Env protein vaccine regimens using two different adjuvants induced durable and potent cellular and humoral responses contributing to a lower risk of infection by heterologous SIV challenge. © 2018 American Society for Microbiology.
Filiaciones:
Singh S.:
Human Retrovirus Pathogenesis Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD, United States
Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, CA, United States
Ramírez-Salazar E.G.:
Human Retrovirus Pathogenesis Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD, United States
Consejo Nacional de Ciencia y Tecnología (CONACYT), Laboratorio de Genómica del Metabolismo óseo, Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City, Mexico
Doueiri R.:
Human Retrovirus Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD, United States
Valentin A.:
Human Retrovirus Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD, United States
Rosati M.:
Human Retrovirus Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD, United States
Hu X.:
Human Retrovirus Pathogenesis Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD, United States
Keele B.F.:
AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, United States
Shen X.:
Duke Human Vaccine Institute, Department of Medicine, Duke University Medical Center, Durham, NC, United States
Tomaras G.D.:
Duke Human Vaccine Institute, Department of Immunology, Duke University Medical Center, Durham, NC, United States
Duke Human Vaccine Institute, Department of Molecular Genetics, Duke University Medical Center, Durham, NC, United States
Duke Human Vaccine Institute, Department of Surgery, Duke University Medical Center, Durham, NC, United States
Ferrari G.:
Duke Human Vaccine Institute, Department of Molecular Genetics, Duke University Medical Center, Durham, NC, United States
Duke Human Vaccine Institute, Department of Surgery, Duke University Medical Center, Durham, NC, United States
LaBranche C.:
Duke Human Vaccine Institute, Department of Surgery, Duke University Medical Center, Durham, NC, United States
Montefiori D.C.:
Duke Human Vaccine Institute, Department of Surgery, Duke University Medical Center, Durham, NC, United States
Das J.:
Ragon Institute of MGH, MIT, Harvard University, Cambridge, MA, United States
Alter G.:
Ragon Institute of MGH, MIT, Harvard University, Cambridge, MA, United States
Trinh H.V.:
U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, United States
Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, United States
Hamlin C.:
U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, United States
Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, United States
Rao M.:
U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, United States
Dayton F.:
Human Retrovirus Pathogenesis Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD, United States
Bear J.:
Human Retrovirus Pathogenesis Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD, United States
Chowdhury B.:
Human Retrovirus Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD, United States
Alicea C.:
Human Retrovirus Pathogenesis Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD, United States
Lifson J.D.:
AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, United States
Broderick K.E.:
Inovio Pharmaceuticals, Inc., Plymouth Meeting, PA, United States
Sardesai N.Y.:
Inovio Pharmaceuticals, Inc., Plymouth Meeting, PA, United States
Sivananthan S.J.:
Infectious Disease Research Institute, Seattle, WA, United States
Fox C.B.:
Infectious Disease Research Institute, Seattle, WA, United States
Reed S.G.:
Infectious Disease Research Institute, Seattle, WA, United States
Venzon D.J.:
Biostatistics and Data Management Section, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Rockville, MD, United States
Hirsch V.M.:
Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States
Pavlakis G.N.:
Human Retrovirus Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD, United States
Felber B.K.:
Human Retrovirus Pathogenesis Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD, United States
All Open Access, Hybrid Gold
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