Peptide-Based HIV Vaccine Produces Antibody Response in Monkeys Without Using Viral Genetic Material, But More Research Needed

A new experimental AIDS vaccine, which uses peptides from "wholly unrelated" viruses called phages but no genetic material from HIV, produced antibody responses in monkeys that protected them from infections with a "virulent" AIDS virus, the Wall Street Journal reports. National Institute for Allergy and Infectious Diseases Director Anthony Fauci and Giuseppe Scala of NIAID and the University of Catanzaro in Italy report on the experiment in this month's Nature Medicine. Their research team engineered phages, viruses that infect bacteria, to produce "millions of random peptides," which they then combined with HIV antibodies in test-tube studies in an attempt to discern which peptides, if any, might be "useful" in an AIDS vaccine. They then vaccinated five monkeys with the most promising peptides. Four of the five monkeys produced HIV antibodies and were then injected with a virulent AIDS virus. All four monkeys remained healthy, while all seven control monkeys became ill or died. Calling the vaccine candidate "potentially very exciting," David Montefiori, an HIV antibody expert at the Center for AIDS Research at Duke University, said that the study "didn't completely rule out" whether the antibody response or a possible secondary immune response triggered by the peptides was responsible for protecting the monkeys. "It could be antibodies conferring this mild protection, but it's not entirely clear because other immune responses weren't thoroughly examined," he noted. Other experts added that because the one monkey that did not respond to the vaccine was not included in the statistical analysis, the results were skewed, making them seem "more promising" than if the one monkey had been included. They also noted that the results were still not as strong as those produced in studies of other vaccines that sought to induce killer T-cell responses.

A Different Approach
Most vaccine candidates today are designed to stimulate "another arm" of the immune system by invoking a killer T-cell response. Although antibody-producing vaccines have been successful against diseases such as polio and measles, the approach has proved "very difficult" with HIV because of the virus' ability to mutate rapidly. Most antibody-producing vaccines have only been able to work against one strain of HIV, but a person with the virus may harbor a "swarm" of different strains, the Journal says. While early candidates like Vaxgen's AIDSVAX use the antibody approach, most researchers have focused on killer T-cell vaccines, which may not protect completely against infection, but have kept animals alive well after exposure to HIV-like viruses. Most researchers believe that a successful vaccine will require a combination of the two strategies to outwit HIV (Schoofs, Wall Street Journal, 11/1).

HHV-6 Blocks HIV Receptor
In a separate study published in Nature Medicine, researchers from the National Institute of Child Health and Human Development and the San Raffaele Scientific Institute in Milan, Italy, found that the "apparently harmless" human herpes virus 6 (HHV-6) may slow HIV progression by producing a molecule that binds to CCR5, a receptor HIV needs to enter cells, thereby blocking HIV from entering cells and reproducing. However, HHV-6 may only offer limited protection because HIV strains that develop in later stages of the disease can bind to CXCR4, a different receptor (NIH release, 10/31). These later strains that use the CXCR4 receptor are also "more virulent" and could cause illness and death sooner, the Journal reports.

Protein 'Short-Circuits' Apoptosis
In a third study published in Nature Medicine, German researchers found that nef, a protein found in HIV, "short-circuits" apoptosis, the process by which infected cells commit "suicide." Cells use apoptosis as a defense mechanism, eliminating themselves when they are infected with viruses. Nef, which disrupts several immune functions, keeps the cells alive, allowing HIV to replicate and spread (Wall Street Journal, 11/1).