Comparison of intradermal and intramuscular delivery followed by in vivo electroporation of SIV Env DNA in macaques

Viraj Kulkarni, Margherita Rosati, Jenifer Bear, Guy R. Pilkington, Rashmi Jalah, Cristina Bergamaschi, Ashish K. Singh, Candido Alicea, Bhabadeb Chowdhury, Gen Mu Zhang, Eun Young Kim, Steven M. Wolinsky, Wensheng Huang, Yongjun Guan, Celia La Branche, David C. Montefiori, Kate E. Broderick, Niranjan Y. Sardesai, Antonio Valentin, Barbara K. Felber*George N. Pavlakis

*Corresponding author for this work

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

A panel of SIVmac251 transmitted Env sequences were tested for expression, function and immunogenicity in mice and macaques. The immunogenicity of a DNA vaccine cocktail expressing SIVmac239 and three transmitted SIVmac251 Env sequences was evaluated upon intradermal or intramuscular injection followed by in vivo electroporation in macaques using sequential vaccination of gp160, gp120 and gp140 expressing DNAs. Both intradermal and intramuscular vaccination regimens using the gp160 expression plasmids induced robust humoral immune responses, which further improved using the gp120 expressing DNAs. The responses showed durability of binding and neutralizing antibody titers and high avidity for > 1 y. The intradermal DNA delivery regimen induced higher cross-reactive responses able to neutralize the heterologous tier IB-like SIVsmE660-CG7V. Analysis of cellular immune responses showed induction of Env-specific memory responses and cytotoxic granzyme B+T cells in both vaccine groups, although the magnitude of the responses were ∼10× higher in the intramuscular/electroporation group. The cellular responses induced by both regimens were long lasting and could be detected ∼1 y after the last vaccination. These data show that both DNA delivery methods are able to induce robust and durable immune responses in macaques.

Original languageEnglish (US)
Pages (from-to)2081-2094
Number of pages14
JournalHuman Vaccines and Immunotherapeutics
Volume9
Issue number10
DOIs
StatePublished - Oct 1 2013

Keywords

  • Avidity
  • Binding antibody
  • DNA vaccine
  • Effector memory
  • HIV
  • In vivo electroporation
  • Intradermal
  • Intramuscular
  • Neutralizing antibody
  • SIVmac239
  • SIVmac251
  • SIVsmE660
  • Transitional memory
  • Transmitted Env

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology

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    Kulkarni, V., Rosati, M., Bear, J., Pilkington, G. R., Jalah, R., Bergamaschi, C., Singh, A. K., Alicea, C., Chowdhury, B., Zhang, G. M., Kim, E. Y., Wolinsky, S. M., Huang, W., Guan, Y., La Branche, C., Montefiori, D. C., Broderick, K. E., Sardesai, N. Y., Valentin, A., ... Pavlakis, G. N. (2013). Comparison of intradermal and intramuscular delivery followed by in vivo electroporation of SIV Env DNA in macaques. Human Vaccines and Immunotherapeutics, 9(10), 2081-2094. https://doi.org/10.4161/hv.25473