DNA Vaccine Is Safe And Immunogenic.(Brief Article)

2001 DEC 12 - (NewsRx.com & NewsRx.net) -- Vical, Incorporated, and the U.S. Naval Medical Research Center has announced results of initial Phase II human testing for safety, immunogenicity, and protective efficacy of a multigene DNA vaccine intended to prevent infection by the malaria parasite Plasmodium falciparum (Pf).

The results of this trial provide the basis for planning further development toward a malaria vaccine product.

"This trial was important as it was the first to establish in healthy human volunteers the safety and immunogenicity of a complex, multigene vaccine with or without an additional gene encoding a human cytokine [granulocyte-macrophage colony-stimulating factor (GM-CSF)]," said the U.S. Navy's lead investigator, Capt. Thomas L. Richie, MD, PhD. "We were pleased that DNA immunization primed for the boosting of selected T-cell and antibody responses induced by a brief exposure to pre-erythrocytic stage Pf antigens during the sporozoite challenge. The results of the trial also point the way for future studies to improve the immunogenicity and protective efficacy of DNA vaccines."

David C. Kaslow, MD, Vical, said, "We are pleased with the progress to date and we look forward to continuing our collaboration with the U.S. Navy toward the development of an effective and practical malaria vaccine based on our patented naked DNA technology. We are particularly excited by the confirmation of prime-boost activity. That information will be valuable in planning the next trial design."

Trial results indicated that vaccination was safe and well-tolerated, and caused specific T-cell immune responses against encoded antigens. Although all volunteers contracted the disease, measurements after the challenge indicated specific antibody and T-cell immune responses, and were stronger in volunteers receiving the vaccine than in volunteers who did not receive the vaccine, suggesting a vaccine-induced prime and parasite-induced boost effect. Results were presented at the 50th Annual Meeting of the American Society of Tropical Medicine and Hygiene by Dr. Richie and Yupin Charoenvit, PhD.

Testing was conducted through the U.S. Navy Malaria Program under program director Capt. Daniel J. Carucci, MD, PhD, by a team of investigators led by Richie. The vaccine, designated MuStDO 5, incorporates five genes (PfCSP, PfSSP2, PfEXP1, PfLSA1, and PfLSA3) that are designed to cause production of Pf immunogens and trigger an immune response against the malaria parasite in the sporozoite and liver stages of its life cycle. Earlier clinical testing demonstrated safety and immunogenicity of a single-gene Pf DNA vaccine, and guided dosing and delivery methods.

In this first Phase II controlled challenge trial, the MuStDO 5 DNA vaccine included dose escalation (0 mcg. control vs. 20 mcg., 100 mcg., or 500 mcg.) of a naked DNA agent encoding human GM-CSF (hGM-CSF), a cytokine, or immune system stimulant. Each of the four dosing groups received 2.5 mg. of vaccine at weeks 0, 4, and 8, followed by a Pf sporozoite challenge at week 11 delivered by controlled exposure to infected mosquitoes.