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. 2004 Apr 30;18(7):991-1001.
doi: 10.1097/00002030-200404300-00006.

Immunogenicity of HIV-1 Env and Gag in baboons using a DNA prime/protein boost regimen

Louisa Leung  1 , Indresh K Srivastava, Elaine Kan, Harold Legg, Yide Sun, Catherine Greer, David C Montefiori, Jan zur Megede, Susan W Barnett
Affiliations

Immunogenicity of HIV-1 Env and Gag in baboons using a DNA prime/protein boost regimen

Louisa Leung et al. AIDS. .

Abstract

Objectives: To evaluate the immunogenicity of sequence-modified HIV env and gag in baboons using DNA prime and protein boost strategy.

Methods: Synthetic sequence-modified HIV gene cassettes were constructed that expressed three different forms of Env proteins, gp140, gp140mut and gp140TM, plus or minus a mutation in the protease-cleavage site. These plasmids were used to immunize baboons (Papio cynocephalus). A group of baboons was also immunized with both env and gag DNA followed by p55Gag virus-like particles (VLP) boost.

Results: Modest antibody responses and low or no lymphoproliferative responses were observed following multiple DNA immunizations. In contrast, strong antibodies and substantial antigen-specific lymphoproliferative responses were seen following booster immunizations with oligomeric Env protein (o-gp140US4) in MF59. Neutralizing antibody responses were scored against T cell line adapted HIV-1 strains after the protein boosters, but neutralizing responses were low or absent against homologous and heterologous primary isolate strains. In the group receiving both gag and env vaccines, modest antigen-specific antibody and lymphoproliferative responses were scored after the DNA immunizations; these responses were enhanced several-fold upon boosting with the VLP preparations. The addition of Gag antigen did not interfere with Env-specific antibody responses, but there was a negative effect on the levels of Env-specific lymphoproliferation.

Conclusions: These results highlight the importance of improving the potency of HIV DNA vaccines by enhanced DNA delivery and prime-boost vaccine technologies to generate more robust immune responses in larger animal models. In addition, care must be taken when immunizations with Env and Gag antigens are performed together.

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