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DNA/MVA vaccine for HIV type 1: effects of codon-optimization and the expression of aggregates or virus-like particles on the immunogenicity of the DNA prime.

Publication ,  Journal Article
Smith, JM; Amara, RR; Campbell, D; Xu, Y; Patel, M; Sharma, S; Butera, ST; Ellenberger, DL; Yi, H; Chennareddi, L; Herndon, JG; Wyatt, LS ...
Published in: AIDS Res Hum Retroviruses
December 2004

Recently, a vaccine consisting of DNA priming followed by boosting with modified vaccinia Ankara (MVA) has provided long-term protection of rhesus macaques against a virulent challenge with a chimera of simian and human immunodeficiency viruses. Here, we report studies on the development of the DNA component for a DNA/MVA HIV vaccine for humans. Specifically, we assess the ability of a codon-optimized Gag-expressing DNA and two noncodon-optimized Gag-Pol-Env-expressing DNAs to prime the MVA booster dose. The codon-optimized DNA expressed virus-like particles (VLPs), whereas one of the noncodon-optimized DNAs expressed VLPs and the other expressed aggregates of HIV proteins. The MVA boost expressed Gag-Pol and Env and produced VLPs. Immunogenicity studies in macaques used one intramuscular prime with 600 microg of DNA and two intramuscular boosts with 1 x 10(8) pfu of MVA at weeks 8 and 30. The codon-optimized and noncodon-optimized DNAs proved similar in their ability to prime anti-Gag T cell responses. The aggregate and VLP-expressing Gag-Pol-Env DNAs also showed no significant differences in their ability to prime anti-Env Ab responses. The second MVA booster dose did not increase the peak CD4 and CD8 T cell responses, but increased anti-Env Ab titers by 40- to 90-fold. MVA-only immunizations elicited 10-100 times lower frequencies of T cells and 2-4 lower titers of anti-Env Ab than the Gag-Pol-Env DNA/MVA immunizations. Based on the breadth of the T cell response and a trend toward higher titers of anti-Env Ab, we are moving forward with human trials of the noncodon-optimized VLP-expressing DNA.

Duke Scholars

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Published In

AIDS Res Hum Retroviruses

DOI

ISSN

0889-2229

Publication Date

December 2004

Volume

20

Issue

12

Start / End Page

1335 / 1347

Location

United States

Related Subject Headings

  • Virology
  • Vaccines, DNA
  • Vaccination
  • Macaca mulatta
  • HIV-1
  • HIV Infections
  • Genes, pol
  • Genes, gag
  • Genes, env
  • Codon
 

Citation

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Chicago
ICMJE
MLA
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Smith, J. M., Amara, R. R., Campbell, D., Xu, Y., Patel, M., Sharma, S., … Robinson, H. L. (2004). DNA/MVA vaccine for HIV type 1: effects of codon-optimization and the expression of aggregates or virus-like particles on the immunogenicity of the DNA prime. AIDS Res Hum Retroviruses, 20(12), 1335–1347. https://doi.org/10.1089/aid.2004.20.1335
Smith, James M., Rama Rao Amara, David Campbell, Yan Xu, Milloni Patel, Sunita Sharma, Salvatore T. Butera, et al. “DNA/MVA vaccine for HIV type 1: effects of codon-optimization and the expression of aggregates or virus-like particles on the immunogenicity of the DNA prime.AIDS Res Hum Retroviruses 20, no. 12 (December 2004): 1335–47. https://doi.org/10.1089/aid.2004.20.1335.
Smith JM, Amara RR, Campbell D, Xu Y, Patel M, Sharma S, et al. DNA/MVA vaccine for HIV type 1: effects of codon-optimization and the expression of aggregates or virus-like particles on the immunogenicity of the DNA prime. AIDS Res Hum Retroviruses. 2004 Dec;20(12):1335–47.
Smith, James M., et al. “DNA/MVA vaccine for HIV type 1: effects of codon-optimization and the expression of aggregates or virus-like particles on the immunogenicity of the DNA prime.AIDS Res Hum Retroviruses, vol. 20, no. 12, Dec. 2004, pp. 1335–47. Pubmed, doi:10.1089/aid.2004.20.1335.
Smith JM, Amara RR, Campbell D, Xu Y, Patel M, Sharma S, Butera ST, Ellenberger DL, Yi H, Chennareddi L, Herndon JG, Wyatt LS, Montefiori D, Moss B, McClure HM, Robinson HL. DNA/MVA vaccine for HIV type 1: effects of codon-optimization and the expression of aggregates or virus-like particles on the immunogenicity of the DNA prime. AIDS Res Hum Retroviruses. 2004 Dec;20(12):1335–1347.
Journal cover image

Published In

AIDS Res Hum Retroviruses

DOI

ISSN

0889-2229

Publication Date

December 2004

Volume

20

Issue

12

Start / End Page

1335 / 1347

Location

United States

Related Subject Headings

  • Virology
  • Vaccines, DNA
  • Vaccination
  • Macaca mulatta
  • HIV-1
  • HIV Infections
  • Genes, pol
  • Genes, gag
  • Genes, env
  • Codon