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RESEARCH BRIEFS
Vaccine Shown to Control HIV in Animal ModelAlthough HIV has thwarted many scientists' attempts to design effective AIDS vaccines, researchers at Beth Israel Deaconess Medical Center now report findings that hold promise for slowing or preventing the development of AIDS even if an HIV infection occurs. Their research on rhesus monkeys was published in the Oct. 20 Science.
T cell responses in monkeys were analyzed via IFN-gamma staining assays on day 140 after viral challenge. When incubated with Gag protein from the simian immunodeficiency virus (SIV), cells from monkeys vaccinated with viral DNA plus IL-2/Ig showed a strong response against the virus. Norman Letvin, HMS professor of medicine at BID, and his colleagues postulated that because individuals infected with HIV mount a cytotoxic T lymphocyte (CTL) immune response to the virus but are unable to eradicate it, a vaccine-induced CTL response elicited prior to infection might be able to control the virus enough to prevent clinical disease. They tested their theory by first injecting monkeys with DNA encoding the Gag protein from the simian immuno-deficiency virus (SIV) and the Env protein from HIV-1 and interleukin-2 (IL-2), a cytokine that enhances the immune system. They followed this injection with an intravenous challenge of a chimeric simian–human immunodeficiency virus consisting of the SIV genome containing the HIV-1 env gene instead of the SIV env gene. The vaccinated monkeys developed CTL responses but were unable to fight off the viral challenge. Yet their immune response was greatly enhanced compared to control (sham-immunized) animals, and they experienced no evidence of clinical disease. Control monkeys developed a weak CTL response, high levels of viral replication, and a rapid loss of CD4+ T cells. Disease progression caused half of them to die within 140 days of viral exposure. Optimally vaccinated monkeys experienced strong CTL responses, suppressed levels of viral replication, and stable CD4+ T cell counts. All immunized monkeys survived, disease free, past day 140 after the exposure. The researchers found that viral Gag and Env DNA alone was not an optimal vaccine. Best results were found by augmenting the DNA with purified fusion protein IL-2/Ig, consisting of IL-2 and the Fc portion of immunoglobulin G2, or plasmid DNA encoding IL-2/Ig. These likely provided the second signal necessary to drive proliferation and differentiation of virus-specific CTLs. The results are a continuation of Letvin's work on fortifying DNA vaccines against the AIDS virus, recently published in the April 11 PNAS (and reported in the April 21 Focus). Optimal Screening Strategy Formulated for Colorectal CancerScreening for colorectal cancer is as cost effective as other forms of cancer screening, and deaths from the disease can be significantly reduced with even a single colonoscopy at age 55, according to a study by researchers at HMS and HSPH. The study is published in the Oct. 18 JAMA. Colorectal cancer screening is done by a variety of methods, including fecal occult blood testing, colonoscopy, and sigmoidoscopy, which can detect not only cancer but the adenomatous polyps that often turn cancerous if not removed. Screening has been shown to reduce mortality, but the most cost-effective strategy—the optimal combination of tests, age at initial screening, and screening interval—has remained uncertain. In the new study, first author A. Lindsay Frazier, HMS assistant professor of pediatrics at the Dana–Farber Cancer Institute, and colleagues developed a statistical model and applied it to available data on colon polyp and colorectal cancer prevalence and the effectiveness and costs of various screening tests to estimate the cost-effectiveness of 22 different screening strategies, calculating incremental cost-effectiveness ratios for each strategy compared with the next least expensive one. A recent panel recommended that average-risk individuals begin screening at age 50 with any one of several strategies. Assumptions about the proportion of the population who undergo screening affected the results substantially. With screening compliance assumed to be 60 percent, the most effective strategy was annual rehydrated fecal occult blood testing plus sigmoidoscopy every five years (with colonoscopy if a polyp was found) from age 50 to 85 years. This strategy, which is one of those commonly recommended, reduced colorectal cancer incidence by 60 percent and mortality by 80 percent compared with no screening. Compliance of 100 percent would be expected to produce similar mortality reductions with a 10-year sigmoidoscopy interval. The authors point out that compliance for colorectal cancer screening is currently quite low in the U.S. "Given the low proportion of Americans who currently comply with the recommended screening schedule, advising all Americans to be screened at least once may be a reasonable starting point for national policy," they write. Among the one-time screening alternatives, colonoscopy was the most effective option, with a lifetime reduction in colorectal cancer mortality of 31 percent and an incremental cost-effectiveness ratio of $22,400 per life-year saved. Colorectal cancer is the second leading cause of cancer-related mortality in the U.S., resulting in approximately 56,600 deaths in 1999. |
