Native HIV Type 1 Virion Surface Structures: Relationships between Antibody Binding and Neutralization or Lessons from the Viral Capture Assay

Despite a vigorous antibody response following HIV-1 infection, antibodies which neutralize primary isolates tend to be of low titer or sporadic. Similarly, antibodies produced in response to HIV-1 vaccines in human and animals react with HIV but, only on occasion, do these antibodies neutralize primary isolates. The failure of the immune system to respond in an effective manner is related to the inherent structural properties of the HIV-1 envelope expressed on the native virion and the pathogenesis of HIV infection. Identification of effective antibody interactions with HIV, as judged by inhibition of virus, is crucial for the development of broadly effective HIV vaccines and immune therapeutics. It has been proposed that antibodies must bind and neutralize virus to be effective at controlling HIV infection. We propose that this hypothesis may limit the identification of effective antibodies that are desperately needed given the difficulty in preventing and treating HIV. We provide evidence that the viral capture assay (VCA) is an important adjunct to the study of antibody interactions with primary isolate virus. Further, we propose that antibodies that are ineffective in traditional neutralization assays may also be effective at limiting viral spread and preventing viral infection.