Chemokine-adjuvanted electroporated DNA vaccine induces substantial protection from simian immunodeficiency virus vaginal challenge.

Autor: Kutzler MA; Division of Infectious Diseases and HIV Medicine, The Department of Medicine, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA., Wise MC; Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, U.S.A., Hutnick NA; Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, U.S.A., Moldoveanu Z; Department of Microbiology and Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA., Hunter M; Tulane National Primate Research Center and the Department of Tropical Medicine, School of Public Health and Tropical Medicine, Tulane University, Covington, Louisiana, USA., Reuter M; Department of Microbiology and Immunology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA., Yuan S; Department of Microbiology and Immunology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA., Yan J; Inovio Pharmaceuticals, Plymouth Meeting, Pennsylvania, USA., Ginsberg A; Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, U.S.A., Sylvester A; Inovio Pharmaceuticals, Plymouth Meeting, Pennsylvania, USA., Pahar B; Tulane National Primate Research Center and the Department of Tropical Medicine, School of Public Health and Tropical Medicine, Tulane University, Covington, Louisiana, USA., Carnathan D; Department of Microbiology and Immunology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA., Kathuria N; Division of Infectious Diseases and HIV Medicine, The Department of Medicine, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA., Khan AS; Inovio Pharmaceuticals, Plymouth Meeting, Pennsylvania, USA., Montefiori D; Human Vaccine Institute, Duke University, Durham, North Carolina, USA., Sardesai NY; Inovio Pharmaceuticals, Plymouth Meeting, Pennsylvania, USA., Betts MR; Department of Microbiology and Immunology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA., Mestecky J; Department of Microbiology and Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA., Marx P; Tulane National Primate Research Center and the Department of Tropical Medicine, School of Public Health and Tropical Medicine, Tulane University, Covington, Louisiana, USA., Weiner DB; Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, U.S.A.
Jazyk: angličtina
Zdroj: Mucosal immunology [Mucosal Immunol] 2016 Jan; Vol. 9 (1), pp. 13-23. Date of Electronic Publication: 2015 May 06.
DOI: 10.1038/mi.2015.31
Abstrakt: There have been encouraging results for the development of an effective HIV vaccine. However, many questions remain regarding the quality of immune responses and the role of mucosal antibodies. We addressed some of these issues by using a simian immunodeficiency virus (SIV) DNA vaccine adjuvanted with plasmid-expressed mucosal chemokines combined with an intravaginal SIV challenge in rhesus macaque (RhM) model. We previously reported on the ability of CCR9 and CCR10 ligand (L) adjuvants to enhance mucosal and systemic IgA and IgG responses in small animals. In this study, RhMs were intramuscularly immunized five times with either DNA or DNA plus chemokine adjuvant delivered by electroporation followed by challenge with SIVsmE660. Sixty-eight percent of all vaccinated animals (P<0.01) remained either uninfected or had aborted infection compared with only 14% in the vaccine naïve group. The highest protection was observed in the CCR10L chemokines group, where six of nine animals had aborted infection and two remained uninfected, leading to 89% protection (P<0.001). The induction of mucosal SIV-specific antibodies and neutralization titers correlated with trends in protection. These results indicate the need to further investigate the contribution of chemokine adjuvants to modulate immune responses and the role of mucosal antibodies in SIV/HIV protection.
Databáze: MEDLINE
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