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Effect of plasmid DNA vaccine design and in vivo electroporation on the resulting vaccine-specific immune responses in rhesus macaques.

Publication ,  Journal Article
Luckay, A; Sidhu, MK; Kjeken, R; Megati, S; Chong, S-Y; Roopchand, V; Garcia-Hand, D; Abdullah, R; Braun, R; Montefiori, DC; Rosati, M ...
Published in: J Virol
May 2007

Since human immunodeficiency virus (HIV)-specific cell-mediated immune (CMI) responses are critical in the early control and resolution of HIV infection and correlate with postchallenge outcomes in rhesus macaque challenge experiments, we sought to identify a plasmid DNA (pDNA) vaccine design capable of eliciting robust and balanced CMI responses to multiple HIV type 1 (HIV-1)-derived antigens for further development. Previously, a number of two-, three-, and four-vector pDNA vaccine designs were identified as capable of eliciting HIV-1 antigen-specific CMI responses in mice (M. A. Egan et al., Vaccine 24:4510-4523, 2006). We then sought to further characterize the relative immunogenicities of these two-, three-, and four-vector pDNA vaccine designs in nonhuman primates and to determine the extent to which in vivo electroporation (EP) could improve the resulting immune responses. The results indicated that a two-vector pDNA vaccine design elicited the most robust and balanced CMI response. In addition, vaccination in combination with in vivo EP led to a more rapid onset and enhanced vaccine-specific immune responses. In macaques immunized in combination with in vivo EP, we observed a 10- to 40-fold increase in HIV-specific enzyme-linked immunospot assay responses compared to those for macaques receiving a 5-fold higher dose of vaccine without in vivo EP. This increase in CMI responses translates to an apparent 50- to 200-fold increase in pDNA vaccine potency. Importantly, in vivo EP enhanced the immune response against the less immunogenic antigens, resulting in a more balanced immune response. In addition, in vivo EP resulted in an approximate 2.5-log(10) increase in antibody responses. The results further indicated that in vivo EP was associated with a significant reduction in pDNA persistence and did not result in an increase in pDNA associated with high-molecular-weight DNA relative to macaques receiving the pDNA without EP. Collectively, these results have important implications for the design and development of an efficacious vaccine for the prevention of HIV-1 infection.

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Published In

J Virol

DOI

ISSN

0022-538X

Publication Date

May 2007

Volume

81

Issue

10

Start / End Page

5257 / 5269

Location

United States

Related Subject Headings

  • Virology
  • Vaccines, DNA
  • Plasmids
  • Neutralization Tests
  • Models, Animal
  • Male
  • Macaca mulatta
  • Leukocytes, Mononuclear
  • Interferon-gamma
  • Humans
 

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Luckay, A., Sidhu, M. K., Kjeken, R., Megati, S., Chong, S.-Y., Roopchand, V., … Egan, M. A. (2007). Effect of plasmid DNA vaccine design and in vivo electroporation on the resulting vaccine-specific immune responses in rhesus macaques. J Virol, 81(10), 5257–5269. https://doi.org/10.1128/JVI.00055-07
Luckay, Amara, Maninder K. Sidhu, Rune Kjeken, Shakuntala Megati, Siew-Yen Chong, Vidia Roopchand, Dorys Garcia-Hand, et al. “Effect of plasmid DNA vaccine design and in vivo electroporation on the resulting vaccine-specific immune responses in rhesus macaques.J Virol 81, no. 10 (May 2007): 5257–69. https://doi.org/10.1128/JVI.00055-07.
Luckay A, Sidhu MK, Kjeken R, Megati S, Chong S-Y, Roopchand V, et al. Effect of plasmid DNA vaccine design and in vivo electroporation on the resulting vaccine-specific immune responses in rhesus macaques. J Virol. 2007 May;81(10):5257–69.
Luckay, Amara, et al. “Effect of plasmid DNA vaccine design and in vivo electroporation on the resulting vaccine-specific immune responses in rhesus macaques.J Virol, vol. 81, no. 10, May 2007, pp. 5257–69. Pubmed, doi:10.1128/JVI.00055-07.
Luckay A, Sidhu MK, Kjeken R, Megati S, Chong S-Y, Roopchand V, Garcia-Hand D, Abdullah R, Braun R, Montefiori DC, Rosati M, Felber BK, Pavlakis GN, Mathiesen I, Israel ZR, Eldridge JH, Egan MA. Effect of plasmid DNA vaccine design and in vivo electroporation on the resulting vaccine-specific immune responses in rhesus macaques. J Virol. 2007 May;81(10):5257–5269.

Published In

J Virol

DOI

ISSN

0022-538X

Publication Date

May 2007

Volume

81

Issue

10

Start / End Page

5257 / 5269

Location

United States

Related Subject Headings

  • Virology
  • Vaccines, DNA
  • Plasmids
  • Neutralization Tests
  • Models, Animal
  • Male
  • Macaca mulatta
  • Leukocytes, Mononuclear
  • Interferon-gamma
  • Humans