Recombinant viral peptide vaccines may enhance, rather thanprevent, infection by such viruses as HIV-1 (humanimmunodeficiency virus), which leads to AIDS, caution Swissresearchers in today's edition of Science.
Stephan Oehen and co-workers at the University of Zurich inSwitzerland's showed that mice immunized with peptides fromlymphocytic choriomeningitis virus (LCMV) were more likely todevelop LCM when challenged by the virus than miceimmunized with a whole LCM virus vaccine.
Like AIDS, LCM is a disease in which T cells (white blood cellsthat direct the immune response) kill virus-infected cells. Butthe T cells cause cellular damage in the process. The Swiss teamproposes that a vaccine may either cause or prevent a disease,depending on the balance between spread of the virus andinduction of an immune response.
The study suggests that peptide vaccines, which contain only asubset of viral antigenic determinants, trigger a response thatleaves the host vulnerable to infection and cell damage. Wholevirus vaccines, in contrast, are more likely to trigger immunity.The mechanisms underlying these actions are unknown.
Several companies, including MicroGeneSys Inc., ViralTechnologies Inc., Repligen Corp., Genentech Inc., Chiron Corp.and Bristol-Myers Squibb, are developing HIV protein- andpeptide-based AIDS vaccines.
MicroGeneSys has extensively tested in the clinic its HIVenvelope protein gp160. The company has so far seen noevidence that the vaccine enhances HIV infectivity, saidFranklin Volvovitz, MicroGenSys' president.
Although the Swiss study is interesting, its relevancy isdifficult to gauge, Volvovitz told BioWorld. Researchers haveknown for some time that peptides, denatured proteins andinactivated viruses can lead to enhancement of the disease, hesaid.
Although unfamiliar with the article, Dr. Scott Putney, aRepligen vice president who heads the company's AIDS vaccineprogram, said that many reports validate peptide vaccines'ability to protect animals from viral infection.
Repligen is developing peptide AIDS vaccines based onconserved sequences in the V3 loop of the HIV gp120 envelopeprotein. Putney said that scientists at France's Institut Pasteurrecently showed that V3 loop peptides protect chimpanzeesfrom HIV infection.
The Swiss team's vaccines consisted of LCM peptides insertedinto vaccinia virus carriers. The researchers listed severalfactors that influenced the ability of LCMV peptide vaccines tocause LCM. They include the genetic background of the mouse,the viral strain used for infection and the immunizationprotocol.
-- Carol Talkington Verser, Ph.D. Special to BioWorld
(c) 1997 American Health Consultants. All rights reserved.