HIV Env antibodies can provide sterilizing immunity in the strictest sense

Neutralizing antibodies targeting HIV-1 Env have been shown to prevent systemic infection in non-human primate models of AIDS and in humans. To explore whether these antibodies can inhibit infection of the first cells, challenge viruses based on simian immunodeficiency virus (SIV) were developed that use HIV-1 Env for entry into target cells during the first replication cycle, but then switch to SIV Env usage. Passive immunization of monkeys with antibodies binding to Env of HIV-1, but not SIV, prior to rectal exposure to the switching challenge virus blocked HIV-1 Env-mediated infection events under neutralizing and non-neutralizing conditions. After natural exposure to HIV-1, such a reduction of the number of first infection events should be sufficient to provide sterilizing immunity in the strictest sense in most of the exposed individuals. Blocking infection of the first cell avoids the formation of latently infected cells and may therefore be the best mode of protection.