Some human monoclonal antibodies to HIV may enhance virusinfection rather than neutralize it, researchers at the Universityof California, San Francisco, reported in this week's issue of theProceedings of the National Academy of Sciences.
Jay Levy, Srisakul Kliks et al, reported that antibodies to tworegions on HIV's outer coat, the V3 loop, have shown differenteffects on three distinct strains of the virus -- neutralization,enhancement or resistance to both processes. They noted thatthis finding could be important for development of anenvelope-based vaccine against HIV.
The UCSF researchers stated that their study suggests "cautionin immunization of individuals with the envelope region fromone strain, since the antibodies induced may show aneutralizing effect against the homologous strain but enhancingeffects against other unrelated strains."
In the study, researchers obtained peripheral bloodmononuclear cells (PBMCs) from HIV-seronegative volunteersand isolated three HIV strains from seropositive individuals.Biologically active molecular clones of the three strains weregenerated and infectious viruses from these clones wererecovered and grown in PBMCs.
Only one amino acid in the monoclonal antibodies was differentamong the three strains. When Kliks et al substituted thisamino acid in the neutralization strain with the amino acid ofthe neutralization-resistant strain or the enhanceable strain,both activities were eliminated. Further, they found that "theconversion of this single amino acid in the neutralization-resistant strain to that of the amino acid found in theneutralization-sensitive strain did not confer the ability for thevirus to be neutralized."
However, they reported, "additional changes in neighboringamino acids in the V3 loop succeeded in conferring theneutralization capability."
-- Brenda Sandburg News Editor
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