Off the Wires

January 1, 2007

US researchers recently reported initial phase 1 results from 2 vaccine candidates that successfully produced immune responses in healthy uninfected adults (Gibian JJ. United Press International. November 16, 2006). Eventually, the approach may be used to protect against HIV infection. Barney Graham of the NIH Vaccine Research Center and colleagues performed the tests (Graham BS, Koup RA, Roderer M, et al. J Infect Dis. 2006;194:1650-1660; Catanzaro AT, Koup RA, Roderer M, et al. J Infect Dis. 2006;194:1638-1649).

Progress Made in HIV Vaccine Development
US researchers recently reported initial phase 1 results from 2 vaccine candidates that successfully produced immune responses in healthy uninfected adults (Gibian JJ. United Press International. November 16, 2006). Eventually, the approach may be used to protect against HIV infection. Barney Graham of the NIH Vaccine Research Center and colleagues performed the tests (Graham BS, Koup RA, Roderer M, et al. J Infect Dis. 2006;194:1650-1660; Catanzaro AT, Koup RA, Roderer M, et al. J Infect Dis. 2006;194:1638-1649).

The first candidate was a plasmid DNA-based vaccine that encoded genes from 3 dominant HIV subtypes. The vaccine was found to be safe and well tolerated. At 12 weeks, 97.5% of vacinees had positive CD4+ T-cell responses and 40% had positive CD8+ T-cell responses.

The second candidate used recombinant adenovirus serotype 5 (rAd5) as a vector to deliver genetic clips from the same HIV subtypes as those used in the first vaccine. This vaccine was also well tolerated but led to adverse events, including pain and fever at higher doses. By the fourth week, 93.3% of those immunized experienced positive CD4+ T-cell responses and 60% had positive CD8+ T-cell responses. [CDC HIV/STD/TB Prevention News Update, Friday, December 1, 2006]

Dual Infection Spreads Epidemics in Africa
In a vicious cycle, malaria is both fueling and being fueled by Africa's AIDS epidemicÑhighlighting the need to combat both epidemics simultaneously, according to new research (Neergaard L. Associated Press. December 7, 2006). Researchers studied a mathematical model to figure out how much the epidemics amplify each other.

HIV infection is most transmissible when patients have high HIV RNA levels. Malaria causes just such a temporary 7-fold spike in HIV RNA levels, said Laith Abu-Raddad, lead researcher (Abu-Raddad LJ, Patnaik P, Kublin JG. Science. 2006;314:1603-1606). And immunocompromised HIV patients are also more susceptible to malaria. A malaria-induced HIV viral surge may last 6 to 8 weeks, typically longer than it takes to feel well enough again to engage in sexual activity, he said. In malarial hot spots, persons can be infected once or twice a year.

Using data from Kisumu, Kenya, researchers estimated that malaria may be responsible for 5% of HIV infections and that HIV, in turn, may be responsible for 10% of the bouts of malaria. In total, that translated to 8500 additional HIV infections and 980,000 malaria episodes over 2 decades, said Abu-Raddad.

Researchers suggested targeting HIV patients for antimalaria programs such as bed nets and insecticides against malaria-carrying mosquitoes. Antiretroviral treatment may also decrease the amplitude of a malaria-induced viral spike, said coinvestigator James Kublin, an HIV researcher with the Fred Hutchinson Cancer Research Center in Seattle. [CDC HIV/STD/TB Prevention News Update, Friday, December 8, 2006]

Experiment Uses HIV to Fight HIV
A phase 1 safety and feasibility study involving 5 HIV-positive patients whose treatment was beginning to fail found a promising patient-specific genetic approach to fighting the virus (Fox M. Reuters. November 6, 2006).

Carl June, lead investigator from the University of Pennsylvania School of Medicine in Philadelphia, and colleagues first crippled the virus. "The virus is gutted so that it only has half the size of the original or pathogenic virus," he said. The envelope gene remaining is reversed to express an antisense gene, an anti-HIV envelope gene. June's team then removed samples of each patient's CD4+ T cells, infused those cells with the genetically engineered antisense HIV, and infused the antisense HIV-infected CD4+ T cells back into the same patients (Levine BL, Humeau LM, Boyer J, et al. Proc Natl Acad Sci U S A. 2006;103:17372-17377. Epub 2006 Nov 7. [2006;doi:10.1073/pnas.0608138103]).

The newly infected immune cells began pumping out defective virus. "The particles that are released are . . . sterile. They are nonpathogenic," said June. And 3 years later, not only are none of the patients showing adverse effects, but the immune systems of 4 patients have actually improved. The virus remains partly suppressed.

Phase 2 trials in HIV patients with well-controlled virus are now under way, said June. It is still not certain whether the approach could be useful only in infected patients or would someday prove to be prophylactic for HIV-negative persons, said June.

The candidate therapy is being developed by the Gaithersburg, Md–based VIRxSYS Corp. The studies are partly funded by the National Institute of Allergy and Infectious Diseases. [CDC HIV/STD/TB Prevention News Update, Thursday, November 9, 2006]