Differential induction of anti-V3 crown antibodies with cradle- and ladle-binding modes in response to HIV-1 envelope vaccination

Preetha Balasubramanian, Rajnish Kumar, Constance Williams, Vincenza Itri, Shixia Wang, Shan Lu, Ann Hessell, Nancy Haigwood, Faruk Sinangil, Keith W. Higgins, Lily Liu, Liuzhe Li, Phillipe Nyambi, Miroslaw K. Gorny, Maxim Totrov, Arthur Nadas, Xiang Peng Kong, Susan Zolla-Pazner, Catarina E. Hioe

    Research output: Contribution to journalArticle

    5 Citations (Scopus)

    Abstract

    The V3 loop in the HIV envelope gp120 is one of the immunogenic sites targeted by Abs. The V3 crown in particular has conserved structural elements recognized by cross-reactive neutralizing Abs, indicating 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 two types of anti-V3 crown Abs are generated by vaccination are unknown. This study analyzed the prevalence 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 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 of the two V3 Ab types was elicited in vaccinated humans or animal models, irrespective of HIV-1 envelope clades, envelope constructs (oligomeric or monomeric), and protocols (DNA plus protein or protein alone) used for vaccinations. 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 vaccinations were able to mediate virus neutralization. These data indicate the restricted repertoires and the species-specific differences in the functional V3-specific Ab responses induced by the HIV envelope vaccines. The study implies the need for improving immunogen designs and vaccination strategies to broaden the diversity of Abs in order to target the different conserved epitopes in the V3 loop and, by extension, in the entire HIV envelope.

    Original languageEnglish (US)
    JournalVaccine
    DOIs
    StateAccepted/In press - Aug 18 2016

    Fingerprint

    Human immunodeficiency virus 1
    Crowns
    HIV-1
    Vaccination
    vaccination
    HIV
    antibodies
    Antibodies
    peptides
    neutralization tests
    Macaca
    HIV Envelope Protein gp120
    neutralization
    epitopes
    AIDS Vaccines
    Peptides
    proteins
    animal models
    rabbits
    vaccines

    Keywords

    • Antibodies
    • HIV
    • HIV envelope
    • Mimotopes
    • V3

    ASJC Scopus subject areas

    • Molecular Medicine
    • Immunology and Microbiology(all)
    • veterinary(all)
    • Public Health, Environmental and Occupational Health
    • Infectious Diseases

    Cite this

    Differential induction of anti-V3 crown antibodies with cradle- and ladle-binding modes in response to HIV-1 envelope vaccination. / Balasubramanian, Preetha; Kumar, Rajnish; Williams, Constance; Itri, Vincenza; Wang, Shixia; Lu, Shan; Hessell, Ann; Haigwood, Nancy; Sinangil, Faruk; Higgins, Keith W.; Liu, Lily; Li, Liuzhe; Nyambi, Phillipe; Gorny, Miroslaw K.; Totrov, Maxim; Nadas, Arthur; Kong, Xiang Peng; Zolla-Pazner, Susan; Hioe, Catarina E.

    In: Vaccine, 18.08.2016.

    Research output: Contribution to journalArticle

    Balasubramanian, P, Kumar, R, Williams, C, Itri, V, Wang, S, Lu, S, Hessell, A, Haigwood, N, Sinangil, F, Higgins, KW, Liu, L, Li, L, Nyambi, P, Gorny, MK, Totrov, M, Nadas, A, Kong, XP, Zolla-Pazner, S & Hioe, CE 2016, 'Differential induction of anti-V3 crown antibodies with cradle- and ladle-binding modes in response to HIV-1 envelope vaccination', Vaccine. https://doi.org/10.1016/j.vaccine.2016.11.107
    Balasubramanian, Preetha ; Kumar, Rajnish ; Williams, Constance ; Itri, Vincenza ; Wang, Shixia ; Lu, Shan ; Hessell, Ann ; Haigwood, Nancy ; Sinangil, Faruk ; Higgins, Keith W. ; Liu, Lily ; Li, Liuzhe ; Nyambi, Phillipe ; Gorny, Miroslaw K. ; Totrov, Maxim ; Nadas, Arthur ; Kong, Xiang Peng ; Zolla-Pazner, Susan ; Hioe, Catarina E. / Differential induction of anti-V3 crown antibodies with cradle- and ladle-binding modes in response to HIV-1 envelope vaccination. In: Vaccine. 2016.
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    abstract = "The V3 loop in the HIV envelope gp120 is one of the immunogenic sites targeted by Abs. The V3 crown in particular has conserved structural elements recognized by cross-reactive neutralizing Abs, indicating 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 two types of anti-V3 crown Abs are generated by vaccination are unknown. This study analyzed the prevalence 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 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 of the two V3 Ab types was elicited in vaccinated humans or animal models, irrespective of HIV-1 envelope clades, envelope constructs (oligomeric or monomeric), and protocols (DNA plus protein or protein alone) used for vaccinations. 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 vaccinations were able to mediate virus neutralization. These data indicate the restricted repertoires and the species-specific differences in the functional V3-specific Ab responses induced by the HIV envelope vaccines. The study implies the need for improving immunogen designs and vaccination strategies to broaden the diversity of Abs in order to target the different conserved epitopes in the V3 loop and, by extension, in the entire HIV envelope.",
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    AU - Balasubramanian, Preetha

    AU - Kumar, Rajnish

    AU - Williams, Constance

    AU - Itri, Vincenza

    AU - Wang, Shixia

    AU - Lu, Shan

    AU - Hessell, Ann

    AU - Haigwood, Nancy

    AU - Sinangil, Faruk

    AU - Higgins, Keith W.

    AU - Liu, Lily

    AU - Li, Liuzhe

    AU - Nyambi, Phillipe

    AU - Gorny, Miroslaw K.

    AU - Totrov, Maxim

    AU - Nadas, Arthur

    AU - Kong, Xiang Peng

    AU - Zolla-Pazner, Susan

    AU - Hioe, Catarina E.

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    N2 - The V3 loop in the HIV envelope gp120 is one of the immunogenic sites targeted by Abs. The V3 crown in particular has conserved structural elements recognized by cross-reactive neutralizing Abs, indicating 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 two types of anti-V3 crown Abs are generated by vaccination are unknown. This study analyzed the prevalence 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 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 of the two V3 Ab types was elicited in vaccinated humans or animal models, irrespective of HIV-1 envelope clades, envelope constructs (oligomeric or monomeric), and protocols (DNA plus protein or protein alone) used for vaccinations. 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 vaccinations were able to mediate virus neutralization. These data indicate the restricted repertoires and the species-specific differences in the functional V3-specific Ab responses induced by the HIV envelope vaccines. The study implies the need for improving immunogen designs and vaccination strategies to broaden the diversity of Abs in order to target the different conserved epitopes in the V3 loop and, by extension, in the entire HIV envelope.

    AB - The V3 loop in the HIV envelope gp120 is one of the immunogenic sites targeted by Abs. The V3 crown in particular has conserved structural elements recognized by cross-reactive neutralizing Abs, indicating 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 two types of anti-V3 crown Abs are generated by vaccination are unknown. This study analyzed the prevalence 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 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 of the two V3 Ab types was elicited in vaccinated humans or animal models, irrespective of HIV-1 envelope clades, envelope constructs (oligomeric or monomeric), and protocols (DNA plus protein or protein alone) used for vaccinations. 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 vaccinations were able to mediate virus neutralization. These data indicate the restricted repertoires and the species-specific differences in the functional V3-specific Ab responses induced by the HIV envelope vaccines. The study implies the need for improving immunogen designs and vaccination strategies to broaden the diversity of Abs in order to target the different conserved epitopes in the V3 loop and, by extension, in the entire HIV envelope.

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