Vaccine targeting SIVmac251 protease cleavage sites protects macaques against vaginal infection.

Autor:	Li H; Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, Manitoba, Canada., Omange RW; Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, Manitoba, Canada., Liang B; National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada.; Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, Manitoba, Canada., Toledo N; Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, Manitoba, Canada., Hai Y; Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, Manitoba, Canada., Liu LR; Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, Manitoba, Canada., Schalk D; Scientific Protocol Implementation Unit, Wisconsin National Primate Research Center, Madison, Wisconsin, USA., Crecente-Campo J; Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Campus Vida, Universidade de Santiago de Compostela, Santiago de Compostela, Spain., Dacoba TG; Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Campus Vida, Universidade de Santiago de Compostela, Santiago de Compostela, Spain., Lambe AB; Sightline Innovation, Toronto, Ontario, Canada., Lim SY; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA., Li L; National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada., Kashem MA; Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, Manitoba, Canada., Wan Y; Nebraska Center for Virology, School of Biological Sciences, University of Nebraska-Lincoln, Lincoln, Nebraska, USA., Correia-Pinto JF; Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Campus Vida, Universidade de Santiago de Compostela, Santiago de Compostela, Spain., Seaman MS; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA., Liu XQ; Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, Manitoba, Canada.; Department of Obstetrics, Gynecology and Reproductive Sciences, University of Manitoba, Winnipeg, Manitoba, Canada., Balshaw RF; Centre for Healthcare Innovation, University of Manitoba, Winnipeg, Manitoba, Canada., Li Q; Nebraska Center for Virology, School of Biological Sciences, University of Nebraska-Lincoln, Lincoln, Nebraska, USA., Schultz-Darken N; Scientific Protocol Implementation Unit, Wisconsin National Primate Research Center, Madison, Wisconsin, USA., Alonso MJ; Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Campus Vida, Universidade de Santiago de Compostela, Santiago de Compostela, Spain., Plummer FA; Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, Manitoba, Canada.; National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada., Whitney JB; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.; Ragon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts, USA., Luo M; Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, Manitoba, Canada.; National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada.
Jazyk:	angličtina
Zdroj:	The Journal of clinical investigation [J Clin Invest] 2020 Dec 01; Vol. 130 (12), pp. 6429-6442.
DOI:	10.1172/JCI138728
Abstrakt:	After over 3 decades of research, an effective anti-HIV vaccine remains elusive. The recently halted HVTN702 clinical trial not only further stresses the challenge to develop an effective HIV vaccine but also emphasizes that unconventional and novel vaccine strategies are urgently needed. Here, we report that a vaccine focusing the immune response on the sequences surrounding the 12 viral protease cleavage sites (PCSs) provided greater than 80% protection to Mauritian cynomolgus macaques against repeated intravaginal SIVmac251 challenges. The PCS-specific T cell responses correlated with vaccine efficacy. The PCS vaccine did not induce immune activation or inflammation known to be associated with increased susceptibility to HIV infection. Machine learning analyses revealed that the immune microenvironment generated by the PCS vaccine was predictive of vaccine efficacy. Our study demonstrates, for the first time to our knowledge, that a vaccine which targets only viral maturation, but lacks full-length Env and Gag immunogens, can prevent intravaginal infection in a stringent macaque/SIV challenge model. Targeting HIV maturation thus offers a potentially novel approach to developing an effective HIV vaccine.
Databáze:	MEDLINE
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