title: Broad cross-neutralizing activity in serum is associated with slow progression and low risk of transmission in primate lentivirus infections.
abstract: Sera from human immunodeficiency virus type 1 and type 2 (HIV-1 and HIV-2)-infected humans were tested with autologous (from the same individual) and heterologous (from other individuals) virus isolates in a neutralization assay. Similarly, sera from experimentally simian immunodeficiency virus (SIVsm from sooty mangabey) or HIV-2SBL6669-infected cynomolgus macaques were tested for neutralizing activity against autologous and heterologous reisolates. In the neutralization assay, the virus dose ranged between 10-75 50% infectious dose (ID50), sera were used in five 2- or 4-fold dilutions, beginning with 1:20, and human peripheral blood mononuclear cells (PBMCs) served as target cells. The readout of the 7-day assay was a HIV-1 or HIV-2 antigen enzyme-linked immunosorbent assay (ELISA). Our results show that SIVsm-inoculated monkeys who develop early immunodeficiency lack serum neutralizing activity or develop a neutralizing antibody response with narrow specificity. Long survival is associated with the ability to neutralize several autologous and heterologous SIVsm reisolates. Infection of macaques with HIV-2SBL6669 did not cause disease within the 5 years observation time and elicited a broadly cross-reactive neutralizing antibody response, including neutralization of other, independently obtained, HIV-2 isolates. In HIV-1-infected humans, neutralizing antibodies can only be detected in up to 50% of cases. Neutralizing activity, whenever present, may show a broad specificity, that is, neutralization may occur across genetic subtypes. Presence of broadly cross-reactive neutralizing antibodies is associated with a lower risk of HIV-1 (subtype B) transmission both from mother to child and sexually from male to female. Unlike HIV-1 infection, serum neutralizing activity is regularly present in HIV-2 infection. In view of the differences between HIV-1 and HIV-2 pathogenesis, we suggest that an effective neutralizing antibody response may contribute to a delay in disease progression and to a decrease in risk of transmission.
authors.affiliation: Microbiology and Tumorbiology Center, Karolinska Institute, Stockholm, Sweden.
authors.forename: E M
authors.initials: EM
authors.lastname: Fenyö
authors.forename: P
authors.initials: P
authors.lastname: Putkonen
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood* / Q000276:immunology*; D001667:Binding, Competitive / Q000276:immunology; D016665:Cercocebus atys; D003429:Cross Reactions / Q000276:immunology; D018450:Disease Progression; D005260:Female; D015497:HIV-1 / Q000276:immunology; D015498:HIV-2 / Q000276:immunology; D006801:Humans; D018445:Infectious Disease Transmission, Vertical; D016180:Lentivirus Infections / Q000276:immunology* / Q000635:transmission*; D017958:Lentiviruses, Primate / Q000276:immunology*; D008253:Macaca mulatta; D008297:Male; D009500:Neutralization Tests; D015302:Simian Immunodeficiency Virus / Q000276:immunology
chemical_list: D000914:Antibodies, Viral