Abstract

We optimize DNA vaccine procedures for AIDS and eventually other applications. We used optimization of antigen form, expression and delivery to achieve optimal results. The optimized DNA vectors were shown to provide protection from high viremia in both prophylactic and therapeutic vaccination of rhesus macaques infected by SIV, the most faithful primate model for AIDS. We have used molecular adjuvants to increase immune response to DNA vaccination in collaborative studies. We have shown that IL-12 increased both humoral and cellular immune response to SIV DNA vectors in macaques. We have also shown that the optimized DNA is excellent in priming immune response in DNA prime-virus vector boost. The HIV optimized vectors are in clinical trials. The development of several vector combinations from our lab provides the opportunity for additional clinical applications in AIDS and cancer.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Division of Basic Sciences - NCI (NCI)
Type
Intramural Research (Z01)
Project #
1Z01BC010749-01
Application #
7338778
Study Section
Vector Biology Study Section (VB)
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2006
Total Cost
Indirect Cost

  Institution

Name
Basic Sciences
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

Robinson, T M; Sidhu, M K; Pavlakis, G N et al. (2007) Macaques co-immunized with SIVgag/pol-HIVenv and IL-12 plasmid have increased cellular responses. J Med Primatol 36:276-84
von Gegerfelt, Agneta S; Rosati, Margherita; Alicea, Candido et al. (2007) Long-lasting decrease in viremia in macaques chronically infected with simian immunodeficiency virus SIVmac251 after therapeutic DNA immunization. J Virol 81:1972-9
Smulevitch, Sergey; Bear, Jenifer; Alicea, Candido et al. (2006) RTE and CTE mRNA export elements synergistically increase expression of unstable, Rev-dependent HIV and SIV mRNAs. Retrovirology 3:6
Egan, Michael A; Megati, Shakuntala; Roopchand, Vidia et al. (2006) Rational design of a plasmid DNA vaccine capable of eliciting cell-mediated immune responses to multiple HIV antigens in mice. Vaccine 24:4510-23
Schadeck, Eva B; Sidhu, Maninder; Egan, Michael A et al. (2006) A dose sparing effect by plasmid encoded IL-12 adjuvant on a SIVgag-plasmid DNA vaccine in rhesus macaques. Vaccine 24:4677-87
Kumar, Sanjeev; Yan, Jian; Muthumani, Karuppiah et al. (2006) Immunogenicity testing of a novel engineered HIV-1 envelope gp140 DNA vaccine construct. DNA Cell Biol 25:383-92
von Gegerfelt, Agneta S; Alicea, Candido; Valentin, Antonio et al. (2006) Long lasting control and lack of pathogenicity of the attenuated Rev-independent SIV in rhesus macaques. AIDS Res Hum Retroviruses 22:516-28
Egan, Michael A; Chong, Siew Yen; Megati, Shakuntala et al. (2005) Priming with plasmid DNAs expressing interleukin-12 and simian immunodeficiency virus gag enhances the immunogenicity and efficacy of an experimental AIDS vaccine based on recombinant vesicular stomatitis virus. AIDS Res Hum Retroviruses 21:629-43
Boyer, Jean D; Robinson, Tara M; Maciag, Paulo C et al. (2005) DNA prime Listeria boost induces a cellular immune response to SIV antigens in the rhesus macaque model that is capable of limited suppression of SIV239 viral replication. Virology 333:88-101
Kutzler, Michele A; Robinson, Tara M; Chattergoon, Michael A et al. (2005) Coimmunization with an optimized IL-15 plasmid results in enhanced function and longevity of CD8 T cells that are partially independent of CD4 T cell help. J Immunol 175:112-23

Showing the most recent 10 out of 12 publications