AIDSWEEKLY Plus, Monday, 27 Mary 1997.
Daniel J. DeNoon, Senior Editor
Prime/boost vaccination using a new HIV DNA vaccine protected monkeys from infection with a chimeric simian/human immunodeficiency virus (SHIV).
The approach is now being tested in humans, reported Merck researcher Margaret A. Liu in a presentation to the 9th Annual Meeting of the National Cooperative Vaccine Development Groups for AIDS (NCVDG), held May 4-7, 1997, in Bethesda, Maryland.
"The potent immunity and protection seen in these pilot experiments suggest that a DNA immunization with a DNA-plus- protein-boost regimen warrants active investigation as a vaccine strategy to prevent HIV-1 infection," Liu wrote in her presentation abstract.
Liu described the Merck DNA vaccine as a bacterial plasmid carrying the HIV Env gene under the control of the cytomegalovirus (CMV) promoter gene sequence. The Env gene is a truncated version of gp160, containing the entire gp120 sequence plus a portion of the gp41 gene.
Pilot studies showed that DNA vaccination of monkeys induced long-lived cytotoxic lymphocyte (CTL) responses. Boosting with recombinant HIV-1 Env protein elicited high titers of neutralizing antibodies.
Rhesus monkeys immunized with DNA encoding Env from HIV-1 strain HXBc2 were boosted with recombinant Env protein from the IIIB strain of the virus. The animals resisted challenge with an infectious SHIV strain based on HXBc2.
"For us, what this pilot study was a road sign showing that we are going in the right direction," Liu said.
Interestingly, Liu and colleagues found that monkeys' immune system responded to immunization with "empty" plasmid vector lacking HIV genes. Control animals vaccinated in this way and boosted with protein had their immune responses driven toward T-helper-type 1 (Th1) responses. Animals that received the DNA vaccine had the same type of responses, while a very different pattern occurred in animals vaccinated with peptide only.
"It appears that the vector itself modulates the immune response," Liu said. "It's clear that the plasmid DNA acts as an adjuvant."
In subsequent green monkey experiments, animals received either HIV Env DNA followed by boosting with both HIV Env DNA and Env protein; protein alone; or "empty" DNA plus ovalbumin.
Only the monkeys in the prime/boost group developed a high-titer neutralizing antibody response; these were the only animals protected against challenge with infectious SHIV
Liu said that human trials of the HIV DNA prime/protein boost approach are underway. - by Daniel J. DeNoon, Senior Editor
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