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

Publication ,  Journal Article
Wang, C; Jiang, C; Gao, N; Zhang, K; Liu, D; Wang, W; Cong, Z; Qin, C; Ganusov, VV; Ferrari, G; LaBranche, C; Montefiori, DC; Kong, W; Yu, X; Gao, F
Published in: Viruses
June 2, 2017

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.

Duke Scholars

Published In

Viruses

DOI

EISSN

1999-4915

Publication Date

June 2, 2017

Volume

9

Issue

6

Location

Switzerland

Related Subject Headings

  • Virus Integration
  • Viral Load
  • Vaccines, Attenuated
  • Simian immunodeficiency virus
  • Simian Immunodeficiency Virus
  • SAIDS Vaccines
  • Macaca mulatta
  • Immunity, Humoral
  • Immunity, Cellular
  • Antibody-Dependent Cell Cytotoxicity
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Wang, C., Jiang, C., Gao, N., Zhang, K., Liu, D., Wang, W., … Gao, F. (2017). Immunologic and Virologic Mechanisms for Partial Protection from Intravenous Challenge by an Integration-Defective SIV Vaccine. Viruses, 9(6). https://doi.org/10.3390/v9060135
Wang, Chu, Chunlai Jiang, Nan Gao, Kaikai Zhang, Donglai Liu, Wei Wang, Zhe Cong, et al. “Immunologic and Virologic Mechanisms for Partial Protection from Intravenous Challenge by an Integration-Defective SIV Vaccine.Viruses 9, no. 6 (June 2, 2017). https://doi.org/10.3390/v9060135.
Wang, Chu, et al. “Immunologic and Virologic Mechanisms for Partial Protection from Intravenous Challenge by an Integration-Defective SIV Vaccine.Viruses, vol. 9, no. 6, June 2017. Pubmed, doi:10.3390/v9060135.
Wang C, Jiang C, Gao N, Zhang K, Liu D, Wang W, Cong Z, Qin C, Ganusov VV, Ferrari G, LaBranche C, Montefiori DC, Kong W, Yu X, Gao F. Immunologic and Virologic Mechanisms for Partial Protection from Intravenous Challenge by an Integration-Defective SIV Vaccine. Viruses. 2017 Jun 2;9(6).

Published In

Viruses

DOI

EISSN

1999-4915

Publication Date

June 2, 2017

Volume

9

Issue

6

Location

Switzerland

Related Subject Headings

  • Virus Integration
  • Viral Load
  • Vaccines, Attenuated
  • Simian immunodeficiency virus
  • Simian Immunodeficiency Virus
  • SAIDS Vaccines
  • Macaca mulatta
  • Immunity, Humoral
  • Immunity, Cellular
  • Antibody-Dependent Cell Cytotoxicity