by Sean Henahan, Access Excellence

BETHESDA, MD- One of the most challenging obstacles facing AIDS vaccine developers is the extensive variability among different strains of the rapidly mutating virus, HIV. Another problem has been the lack of a good animal model for vaccine studies. New research from the National Institutes of Health suggests that neither obstacle is insurmountable.

HIV-1 shows remarkable genetic variability within individuals, within communities, and throughout the world. Eight distinctive subtypes, labeled A through H, have already been identified. This poses a huge challenge to vaccine researchers who have yet to develop a successful prophylactic vaccine against one strain, much less all strains of HIV.

HIV-2 is seen much less frequently in the developed world. This virus shares about half of the structural gene products found in HIV-1. HIV-2, while less infectious than HIV-1, is endemic in parts of Africa and can and does cause AIDS. The bad news is, AIDS vaccines will have to be effective against both HIV-1 and HIV-2. The good news is, HIV-2 may prove to be a source for a vaccine against both.

In the current study, researchers vaccinated eight rhesus macaques with different components of HIV-1 (gag, pol and env genes) combined with attenuated vaccinia or canarypox virus, followed by a boost with HIV-1 protein subunits. To their surprise, half of the macaques were protected against infection when challenged with HIV-2, while all of the animals in the control group got infected. .

"These results provide the first demonstration of cross protection between highly divergent HIVs, suggesting that broad vaccine protection may be achievable. The exciting possibility that immunization with HIV vaccines might give the added bonus of protection against HIV-2 infection would greatly facilitate vaccination programs in West Africa where both HIV-1 and HIV-2 infections are prevalent

"This finding, although preliminary, suggests that viral variability may not necessarily preclude effective AIDS vaccine development. It should encourage further investigation of cross protection in other heterologous systems as well as stimulate research on immunologically conserved epitopes and potentially novel protective mechanisms," note the researchers in Nature Medicine.

The basis for the cross-protection observed in these studies is unknown. The responses did not appear to correlate with observed effects. The humoral and cellular immunity produced by HIV appeared similar in infected and noninfected animals. It is possible the protection resulted from an hitherto unknown mechanism, such as induction of a cytokine or inhibitory factor, they note.

The findings are also good news for researchers who had become pessimistic about the use of animal models for AIDS research. The four main animal models used for retrovirus research are chimpanzees infected with HIV-1, macaque monkeys infected with SIV or HIV-2, cats infected with FIV (feline immunodeficiency virus), and genetically engineered SCID mice with human immune system components infected with HIV. And of course, human trials are currently underway with a number of vaccine candidates.

Chimpanzee studies have yielded some interesting findings. These animals can be infected with HIV but do not get AIDS. Chimpanzees have been successfully immunized against HIV with candidate AIDS vaccines now in human trials. However, chimpanzees are expensive and are considered an endangered species in the wild.

The researchers in this study used rhesus macaques, an animal that is not as hard to obtain as the chimpanzee. This animal is vulnerable to infection with both SIV (simian immunodeficiency virus) and HIV-2. Macaques have become the most widely used animal in vivo AIDS research.

"This unexpected findings of this study challenge many of our prejudices about how to vaccinate and protect against immunodeficiency viruses," note AIDS researchers James Stott and Neil Almond in an accompanying editorial.

The complete study details and accompanying commentary can be found in Nature Medicine, V.1, No.4, 4/4/95, Abiniku et al,. pp. 321-329 and Stott and Almond, pp. 295-297.

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Transmitted: 95-04-01 18:19:53 EST