Multifunctional T cell characteristics induced by a polyvalent DNA prime/protein boost HIV-1 vaccine regimen given to healthy adults are dependant upon the route and dose of administration

Departments of Medicine, Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA 35294; Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USA 01655 and Division of Molecular Medicine, New York State Department of Health, Albany, NY 12201

^* To whom correspondence should be addressed. Email: paulg{at}uab.edu.

	Abstract

A phase I clinical vaccine study of an HIV-1 DNA prime (5-valent env and monovalent gag) followed by a 5-valent Env protein boost in seronegative adults was previously shown to induce HIV-1 specific T cells and anti-Env antibodies capable of neutralizing cross-clade viral isolates. In light of these initial findings, we sought to more fully characterize the HIV-1-specific T cells using polychromatic flow cytometry. Three groups of participants were vaccinated 3 times with either: a) 1.2mg DNA intradermally (ID group); b) 1.2mg DNA intramuscularly (IM group); or c) 7.2mg DNA IM (high dose group). Each group subsequently received one or two doses of the gp120 protein boost (0.375 mg IM). Env-specific CD4 T cell responses were seen in the majority of participants; however, the kinetics of response differed depending on the route of DNA administration. The high dose IM group induced the greatest magnitude of response after the DNA vaccinations while the ID group exhibited the least. Nevertheless, after the second protein boost, the magnitude of CD4 T cell responses in the ID group was indistinguishable from the other two groups. After the DNA vaccinations and the first protein boost, a greater number of polyfunctional Env-specific CD4 T cells (2 functions) were seen in the high dose group. Gag-specific CD4 T cells and Env-specific CD8 T cells were seen only in the high dose group. These studies demonstrate that the route and dose of DNA vaccines significantly impacts the quality of immune responses yielding important information for future vaccine design.