AIDSWEEKLY Plus; Monday, May 4, 1998
Daniel J. DeNoon, Senior Editor
Serum from a person with long-term nonprogressive HIV infection is able to recognize a wide variety of HIV isolates from many different viral subtypes.
These antibodies suggest that this individual mounted an immune response to an HIV antigen capable of eliciting cross-clade neutralization - something no current candidate HIV vaccine antigen can do.
"Further analysis ... should provide insight into the required structure of envelope protein in vaccine," said Gerald V. Quinnan of the Uniformed Services University of the Health Sciences, National Institutes of Health, Bethesda, Maryland.
Quinnan spoke in a presentation to the 1998 Palm Springs Symposium on HIV/AIDS, "Towards an HIV Vaccine: Immunopathogenesis of HIV Infection," held March 5-8, 1998, in Palm Springs, California.
The serum, referred to as HIV Neutralizing Serum 2 or R2, is available through the NIH AIDS Research and Reference Reagent Program. The donor remains healthy, Quinnan said, although his partner died of AIDS. Both were infected with the same virus.
R2 serum neutralizes primary HIV-1 isolates of diverse subtypes.
Quinnan and colleagues extracted DNA from the donor's cryopreserved cells and amplified sequences coding HIV envelope protein. These env genes were then cloned into the pSV7d plasmid and expressed on pseudoviruses (PV) to create R2-PV.
R3-PV could be neutralized by three of three clade A sera, three of three clade C sera, and two of three clade E sera.
Infectivity assays showed R2-PV to be dependent on the CCR5 coreceptor. DNA analysis of the R2 env gene thus far has turned up no gross abnormalities: it has the predicted GPGRAF sequence at the apex of the V3 loop (the principal neutralizing domain of the Env glycoprotein); it has normal glycosylation; and its reading frame appears intact.
"The results are consistent with the possibility that the epitope(s) responsible for induction of cross-clade reactive neutralizing antibodies in donor 2 may be expressed relatively prominently on the R2 ENV," Quinnan wrote in his presentation abstract.
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