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Viruses 2017, 9(6), 135; doi:10.3390/v9060135

Immunologic and Virologic Mechanisms for Partial Protection from Intravenous Challenge by an Integration-Defective SIV Vaccine

1
National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, Jilin, China
2
Key Laboratory for Molecular Enzymology and Engineering, the Ministry of Education, School of Life Sciences, Jilin University, Changchun 130012, Jilin, China
3
Division II of In Vitro Diagnostics for Infectious Diseases, Institute for In Vitro Diagnostics Control, National Institutes for Food and Drug Control, Beijing 100050, China
4
Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences, Beijing 100021, China
5
Comparative Medicine Center, Peking Union Medical College, Beijing 100021, China
6
Department of Microbiology, University of Tennessee, Knoxville, TN 37996, USA
7
Departments of Surgery, Duke University Medical Center, Durham, NC 27710, USA
8
Departments of Medicine, Duke University Medical Center, Durham, NC 27710, USA
Parts of the data were presented at HIV Research for Prevention Partnering for Prevention (HIVR4P), October, 2016, Chicago, Illinois; abstract number: P19.08.
*
Authors to whom correspondence should be addressed.
Academic Editor: Curt Hagedorn
Received: 20 April 2017 / Revised: 20 May 2017 / Accepted: 29 May 2017 / Published: 2 June 2017
(This article belongs to the Section Antivirals & Vaccines)
View Full-Text   |   Download PDF [4922 KB, uploaded 2 June 2017]   |  

Abstract

The suppression of viral loads and identification of selection signatures in non-human primates after challenge are indicators for effective human immunodeficiency virus (HIV)/simian immunodeficiency virus (SIV) vaccines. To mimic the protective immunity elicited by attenuated SIV vaccines, we developed an integration-defective SIV (idSIV) vaccine by inactivating integrase, mutating sequence motifs critical for integration, and inserting the cytomegalovirus (CMV) promoter for more efficient expression in the SIVmac239 genome. Chinese rhesus macaques were immunized with idSIV DNA and idSIV particles, and the cellular and humoral immune responses were measured. After the intravenous SIVmac239 challenge, viral loads were monitored and selection signatures in viral genomes from vaccinated monkeys were identified by single genome sequencing. T cell responses, heterologous neutralization against tier-1 viruses, and antibody-dependent cellular cytotoxicity (ADCC) were detected in idSIV-vaccinated macaques post immunization. After challenge, the median peak viral load in the vaccine group was significantly lower than that in the control group. However, this initial viral control did not last as viral set-points were similar between vaccinated and control animals. Selection signatures were identified in Nef, Gag, and Env proteins in vaccinated and control macaques, but these signatures were different, suggesting selection pressure on viruses from vaccine-induced immunity in the vaccinated animals. Our results showed that the idSIV vaccine exerted some pressure on the virus population early during the infection but future modifications are needed in order to induce more potent immune responses. View Full-Text
Keywords: SIV; vaccine; integration defection; challenge; single genome sequencing SIV; vaccine; integration defection; challenge; single genome sequencing
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Wang, C.; Jiang, C.; Gao, N.; Zhang, K.; Liu, D.; Wang, W.; Cong, Z.; Qin, C.; Ganusov, V.V.; Ferrari, G.; LaBranche, C.; Montefiori, D.C.; Kong, W.; Yu, X.; Gao, F. Immunologic and Virologic Mechanisms for Partial Protection from Intravenous Challenge by an Integration-Defective SIV Vaccine. Viruses 2017, 9, 135.

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