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DNA and virus particle vaccination protects against acquisition and confers control of viremia upon heterologous simian immunodeficiency virus challenge.

Publication ,  Journal Article
Patel, V; Jalah, R; Kulkarni, V; Valentin, A; Rosati, M; Alicea, C; von Gegerfelt, A; Huang, W; Guan, Y; Keele, BF; Bess, JW; Piatak, M ...
Published in: Proc Natl Acad Sci U S A
February 19, 2013

We have previously shown that macaques vaccinated with DNA vectors expressing SIVmac239 antigens developed potent immune responses able to reduce viremia upon high-dose SIVmac251 challenge. To further improve vaccine-induced immunity and protection, we combined the SIVmac239 DNA vaccine with protein immunization using inactivated SIVmac239 viral particles as protein source. Twenty-six weeks after the last vaccination, the animals were challenged intrarectally at weekly intervals with a titrated dose of the heterologous SIVsmE660. Two of DNA-protein coimmunized macaques did not become infected after 14 challenges, but all controls were infected by 11 challenges. Vaccinated macaques showed modest protection from SIVsmE660 acquisition compared with naïve controls (P = 0.050; stratified for TRIM5α genotype). Vaccinees had significantly lower peak (1.6 log, P = 0.0048) and chronic phase viremia (P = 0.044), with 73% of the vaccinees suppressing viral replication to levels below assay detection during the 40-wk follow-up. Vaccine-induced immune responses associated significantly with virus control: binding antibody titers and the presence of rectal IgG to SIVsmE660 Env correlated with delayed SIVsmE660 acquisition; SIV-specific cytotoxic T cells, prechallenge CD4(+) effector memory, and postchallenge CD8(+) transitional memory cells correlated with control of viremia. Thus, SIVmac239 DNA and protein-based vaccine protocols were able to achieve high, persistent, broad, and effective cellular and humoral immune responses able to delay heterologous SIVsmE660 infection and to provide long-term control of viremia. These studies support a role of DNA and protein-based vaccines for development of an efficacious HIV/AIDS vaccine.

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Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

February 19, 2013

Volume

110

Issue

8

Start / End Page

2975 / 2980

Location

United States

Related Subject Headings

  • Virion
  • Viremia
  • Viral Vaccines
  • Viral Load
  • Simian immunodeficiency virus
  • Simian Immunodeficiency Virus
  • Simian Acquired Immunodeficiency Syndrome
  • Rectum
  • Macaca mulatta
  • Immunoglobulin G
 

Citation

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Chicago
ICMJE
MLA
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Patel, V., Jalah, R., Kulkarni, V., Valentin, A., Rosati, M., Alicea, C., … Pavlakis, G. N. (2013). DNA and virus particle vaccination protects against acquisition and confers control of viremia upon heterologous simian immunodeficiency virus challenge. Proc Natl Acad Sci U S A, 110(8), 2975–2980. https://doi.org/10.1073/pnas.1215393110
Patel, Vainav, Rashmi Jalah, Viraj Kulkarni, Antonio Valentin, Margherita Rosati, Candido Alicea, Agneta von Gegerfelt, et al. “DNA and virus particle vaccination protects against acquisition and confers control of viremia upon heterologous simian immunodeficiency virus challenge.Proc Natl Acad Sci U S A 110, no. 8 (February 19, 2013): 2975–80. https://doi.org/10.1073/pnas.1215393110.
Patel V, Jalah R, Kulkarni V, Valentin A, Rosati M, Alicea C, et al. DNA and virus particle vaccination protects against acquisition and confers control of viremia upon heterologous simian immunodeficiency virus challenge. Proc Natl Acad Sci U S A. 2013 Feb 19;110(8):2975–80.
Patel, Vainav, et al. “DNA and virus particle vaccination protects against acquisition and confers control of viremia upon heterologous simian immunodeficiency virus challenge.Proc Natl Acad Sci U S A, vol. 110, no. 8, Feb. 2013, pp. 2975–80. Pubmed, doi:10.1073/pnas.1215393110.
Patel V, Jalah R, Kulkarni V, Valentin A, Rosati M, Alicea C, von Gegerfelt A, Huang W, Guan Y, Keele BF, Bess JW, Piatak M, Lifson JD, Williams WT, Shen X, Tomaras GD, Amara RR, Robinson HL, Johnson W, Broderick KE, Sardesai NY, Venzon DJ, Hirsch VM, Felber BK, Pavlakis GN. DNA and virus particle vaccination protects against acquisition and confers control of viremia upon heterologous simian immunodeficiency virus challenge. Proc Natl Acad Sci U S A. 2013 Feb 19;110(8):2975–2980.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

February 19, 2013

Volume

110

Issue

8

Start / End Page

2975 / 2980

Location

United States

Related Subject Headings

  • Virion
  • Viremia
  • Viral Vaccines
  • Viral Load
  • Simian immunodeficiency virus
  • Simian Immunodeficiency Virus
  • Simian Acquired Immunodeficiency Syndrome
  • Rectum
  • Macaca mulatta
  • Immunoglobulin G