P-C16 Differential Induction of Anti-V3 Crown Antibodies with Cradle and Ladle-Binding Modes in Response to HIV-1 Envelope Vaccination. (March 2017)

• Record Type: Journal Article
• Authors: Kumar, Rajnish; Williams, Constance; Itri, Vincenza; Wang, Shixia; Lu, Shan; Hessell, Ann; Higgins, Keith; Liu, Lily; Haigwood, Nancy; Sinangil, Faruk; Gorny, Miroslaw; Totrov, Max; Kong, Xiang; Nadas, Arthur; Zolla-Pazner, Susan; Hioe, Catarina; Balasubramanian, Preetha
• Is Part Of: Journal of acquired immune deficiency syndromes. Volume 74(2017)Supplement 3
• Publication Date: 2017-03
• Subjects: AIDS (Disease) -- Periodicals; Acquired Immunodeficiency Syndrome -- Periodicals; AIDS (Disease); Periodicals; 616.9792005
• DOI: 10.1097/01.qai.0000513957.70610.16
• Languages: English
• ISSNs: 1525-4135

Abstract

Abstract : The V3 loop in the HIV envelope gp120 is one of the immunogenic sites targeted by virus-neutralizing Abs. The V3 crown in particular has conserved structural elements recognized by cross-reactive Abs, implicating its potential contribution in protection against HIV. Crystallographic analyses of anti-V3 crown mAbs in complex with the V3 peptides have revealed that these mAbs recognize the conserved sites on the V3 crown via two distinct strategies: a cradle-binding mode (V3C) and a ladle-binding (V3L) mode. However, almost all of the anti-V3 crown mAbs studied in the past were isolated from chronically HIV-infected individuals. The extents to which the 2 types of anti-V3 crown Abs are generated by HIV envelope vaccines are unknown. This study analyzed the prevalence and levels of V3C-type and V3L-type Ab responses in HIV- infected individuals and in HIV envelope-immunized humans and animals using peptide mimotopes that distinguish the two V3 Ab types. The results show that both V3L-type and V3C-type Abs were generated by the vast majority of chronically HIV-infected humans, although the V3L-type were more prevalent. In contrast, only one type of V3 Abs was elicited in humans or animal models after receiving the HIV envelope vaccines. Irrespective of the HIV envelopes and immunization regimens used, the V3C-type Abs were produced by vaccinated humans, macaques, and rabbits, whereas the V3L-type Abs were made by mice. The V3C-type and V3L-type Abs generated by the HIV envelope vaccines were able to mediate virus neutralization. These data indicate the restricted repertoires and the species-specific differences in the functional V3 Ab responses induced by the HIV envelope vaccines. The study implicates the need for improving immunogen designs and vaccination strategies to broaden the diversity of Abs and target the different conserved epitopes in the V3 loop and in the HIV envelope as a whole.