ScienceDaily (Dec. 30, 2005) — Researchers have demonstrated a technique that has the potential to reduce the toxicity of vaccines and to make smaller doses more effective, according to a study published in PLoS Pathogens.

Developing vaccines is fraught with challenges, particularly because many candidates carry a high risk of toxic side effects. For example, twenty percent of people immunized against smallpox will suffer side effects.

Wilfred Jefferies, a researcher at the University of British Columbia and senior author of the study, and his colleagues have shown that boosting the production of TAP, an immune system component, can make smaller doses of vaccines more effective.

Smaller vaccine doses would mean reduced side effects and the capacity to immunize more people with less material. "As the approach we have discovered appears to augment immune responses for different pathogens and is not limited to the genetics of the host we vaccinate, this new approach could have far reaching benefits in the field of vaccines," Jefferies said.

Vaccines capitalize on normal immune responses. Viral infections are naturally detected with the aid of special molecules called the major histocompatibility complex (MHC), which alert immune system cells to destroy infected cells. If the same virus infects again, the system is primed and ready to respond more quickly. Vaccines, which are created from disease-causing viruses (or their relatives), provide a harmless first exposure so that future infections are thwarted before they become lethal.

In this study, Jefferies and his colleagues vaccinated mice against the viral relatives of rabies and measles viruses and simultaneously induced the overproduction of one component already part of the immune system, called TAP, which enhances MHC activity. Subsequently, specific "destroyer" cells increased fourfold, compared with traditional vaccination. Since these cells help initiate immunity, the group recognized that they were an important piece of the puzzle, according to Jefferies.

"The pathway works like a machine or factory where increasing the efficiency of one component part can lead to a massive increase in functional output," he said.

Next, using varying doses, the team vaccinated mice against a relative of the smallpox virus. Mice immunized with just one-hundredth the standard dose and induced to overproduce TAP were still able to survive an otherwise lethal viral infection.

"We were surprised that over-expression of TAP would have such a great effect because it implies that it is in limiting amounts normally or is inefficient normally," Jefferies said. "Combining viral antigens with a gene that is involved in their processing appears to be a solution to increasing the efficacy of vaccines in general."

CITATION: Vitalis TZ, Zhang QJ, Alimonti J, Chen SS, Basha G, et al. (2005) Using the TAP component of the antigen processing machinery as a molecular adjuvant. PLoS Pathog 1(3): e36.

Link: http://dx.doi.org/10.1371/journal.ppat.0010036

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