Effect of different promoters on immune responses elicited by HIV-1 gag/ env multigenic DNA vaccine in Macaca mulatta and Macaca nemestrina

Abstract

pCMV–NL Δpol and pAKV–NL Δpol expressed human immunodeficiency virus type 1 (HIV-1) gag and env under the regulation of the human cytomegalovirus (CMV) immediate–early (IE) promoter/enhancer and the endogenous AKV murine leukemia viral long terminal repeat (LTR), respectively. Analysis of the immune responses elicited by direct DNA injection of pCMV–NL Δpol and pAKV–NL Δpol in macaques indicated that generation of the humoral and T-cell proliferative responses correlated directly with the promoter strength of the vaccine DNAs. In Macaca mulatta, pCMV–NL Δpol generated stronger humoral responses and T-cell proliferative responses to Gag and Env using less DNA and fewer number of injections than pAKV–NL Δpol. Similarly, in Macaca nemestrina pCMV–NL Δpol elicited high humoral responses, which persisted long-term and were boostable. Injection of large amounts of pAKV–NL Δpol, in general, failed to produce antibody levels comparable to pCMV–NL Δpol. However, injection of a control animal with large amounts of vector DNA produced a generalized enzyme-linked immunosorbent assay (ELISA) reactivity to HIV-1. The results indicated that generation of high immune responses to HIV-1 cannot be achieved by increasing the vaccine DNA dose and may require high protein expression from the DNA by including a strong promoter or by the use of other boosting agents. Furthermore, safety concerns may arise with increasing the DNA dose that could need additional investigation.