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

pCMV-NLDelta pol and pAKV-NLDelta pol 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- NLDelta pol and pAKV-NLDelta pol in macaques indicated that generation of the humoral and T-cell proliferative responses correlated directly with the promoter strength of the vaccine DNAs. In Mucaca mulatta, pCMV-NLDelta pol generated stronger humoral responses and T-cell proliferative responses to Gag and Env using less DNA and fewer number of injections than pAKV-NLDelta pol Similarly, in Macaca nemestrina pCMV-NLDelta pol elicited high humoral responses, which persisted long-term and were boostable. Injection of large amounts of pAKV-NLDelta pol, in general, failed to produce antibody levels comparable to pCMV-NLDelta pol. 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. Published by Elsevier Science Ltd.