NEW YORK (Reuters Health) - Varying the vector used in a triple-dose vaccine carrying a single HIV gene produced an “unprecedented” CD8+ T cell response in monkeys, Philadelphia researchers report.
Dr. Hildegund C. J. Ertl of the Wistar Institute and her colleagues are now conducting additional trials in monkeys of the triple vaccine using larger inserts, she told Reuters Health.
Many HIV vaccines now under development use human adenovirus as a vector, which poses problems because immunity to this virus is so common, Dr. Ertl and her team point out in the July issue of the Journal of Virology. Also, she added in an interview, most HIV vaccine trials use the same vector repeatedly. “When you use the same vector over and over it doesn’t work as well,” she said.
Two of the vectors Dr. Ertl and her colleagues used in the current study were engineered from chimp adenovirus to avoid pre-existing immunity, while the third was derived from a human adenovirus. All carried the Gag gene.
The researchers gave the triple-vaccine regimen to two groups of four outbred rhesus macaques, varying the order of the vaccines. Immunization triggered CD8+ T cell production at levels higher than seen in any other non-human primate tests of HIV vaccine, Dr. Ertl told Reuters Health. In the highest responder, more than 6% of all CD8+ cells among peripheral blood mononuclear cells were Gag-specific CD8+ cells.
Levels of the CD8+ cells remained “remarkably stable” over time, Dr. Ertl and her colleagues report. “In addition, the monkeys developed Gag-specific interleukin-2-secreting T cells, presumably belonging to the CD4+ T-cell subset, and antibodies to both Gag and the adenoviral vaccine carriers,” they note.
Dr. Ertl told Reuters Health that a vaccine with strong enough CD8+ response could conceivably protect people from HIV infection, rather than just treating the disease.
“For a clinical trial I would envision at least a four-month interval between doses but again this is something that has to be tested in more depth,” she said.
Source: J Virol 2004;78:7392-7399. [ Google search on this article ]
MeSH Headings:Retroviridae Proteins: Viral Core Proteins: Viral Proteins: Viral Structural Proteins: Gene Products, gag: CD8-Positive T-Lymphocytes: Nucleocapsid Proteins: PolyproteinsCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
