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Vaccine induction of antibodies against a structurally heterogeneous site of immune pressure within HIV-1 envelope protein variable regions 1 and 2.

Publication ,  Journal Article
Liao, H-X; Bonsignori, M; Alam, SM; McLellan, JS; Tomaras, GD; Moody, MA; Kozink, DM; Hwang, K-K; Chen, X; Tsao, C-Y; Liu, P; Lu, X; Rao, M ...
Published in: Immunity
January 24, 2013

The RV144 HIV-1 trial of the canary pox vector (ALVAC-HIV) plus the gp120 AIDSVAX B/E vaccine demonstrated an estimated efficacy of 31%, which correlated directly with antibodies to HIV-1 envelope variable regions 1 and 2 (V1-V2). Genetic analysis of trial viruses revealed increased vaccine efficacy against viruses matching the vaccine strain at V2 residue 169. Here, we isolated four V2 monoclonal antibodies from RV144 vaccinees that recognize residue 169, neutralize laboratory-adapted HIV-1, and mediate killing of field-isolate HIV-1-infected CD4(+) T cells. Crystal structures of two of the V2 antibodies demonstrated that residue 169 can exist within divergent helical and loop conformations, which contrasted dramatically with the β strand conformation previously observed with a broadly neutralizing antibody PG9. Thus, RV144 vaccine-induced immune pressure appears to target a region that may be both sequence variable and structurally polymorphic. Variation may signal sites of HIV-1 envelope vulnerability, providing vaccine designers with new options.

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Published In

Immunity

DOI

EISSN

1097-4180

Publication Date

January 24, 2013

Volume

38

Issue

1

Start / End Page

176 / 186

Location

United States

Related Subject Headings

  • Protein Conformation
  • Protein Binding
  • Peptides
  • Molecular Sequence Data
  • Molecular Docking Simulation
  • Immunology
  • Humans
  • HIV Envelope Protein gp120
  • HIV Antibodies
  • Antibodies, Monoclonal
 

Citation

APA
Chicago
ICMJE
MLA
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Liao, H.-X., Bonsignori, M., Alam, S. M., McLellan, J. S., Tomaras, G. D., Moody, M. A., … Haynes, B. F. (2013). Vaccine induction of antibodies against a structurally heterogeneous site of immune pressure within HIV-1 envelope protein variable regions 1 and 2. Immunity, 38(1), 176–186. https://doi.org/10.1016/j.immuni.2012.11.011
Liao, Hua-Xin, Mattia Bonsignori, S Munir Alam, Jason S. McLellan, Georgia D. Tomaras, M Anthony Moody, Daniel M. Kozink, et al. “Vaccine induction of antibodies against a structurally heterogeneous site of immune pressure within HIV-1 envelope protein variable regions 1 and 2.Immunity 38, no. 1 (January 24, 2013): 176–86. https://doi.org/10.1016/j.immuni.2012.11.011.
Liao H-X, Bonsignori M, Alam SM, McLellan JS, Tomaras GD, Moody MA, et al. Vaccine induction of antibodies against a structurally heterogeneous site of immune pressure within HIV-1 envelope protein variable regions 1 and 2. Immunity. 2013 Jan 24;38(1):176–86.
Liao, Hua-Xin, et al. “Vaccine induction of antibodies against a structurally heterogeneous site of immune pressure within HIV-1 envelope protein variable regions 1 and 2.Immunity, vol. 38, no. 1, Jan. 2013, pp. 176–86. Pubmed, doi:10.1016/j.immuni.2012.11.011.
Liao H-X, Bonsignori M, Alam SM, McLellan JS, Tomaras GD, Moody MA, Kozink DM, Hwang K-K, Chen X, Tsao C-Y, Liu P, Lu X, Parks RJ, Montefiori DC, Ferrari G, Pollara J, Rao M, Peachman KK, Santra S, Letvin NL, Karasavvas N, Yang Z-Y, Dai K, Pancera M, Gorman J, Wiehe K, Nicely NI, Rerks-Ngarm S, Nitayaphan S, Kaewkungwal J, Pitisuttithum P, Tartaglia J, Sinangil F, Kim JH, Michael NL, Kepler TB, Kwong PD, Mascola JR, Nabel GJ, Pinter A, Zolla-Pazner S, Haynes BF. Vaccine induction of antibodies against a structurally heterogeneous site of immune pressure within HIV-1 envelope protein variable regions 1 and 2. Immunity. 2013 Jan 24;38(1):176–186.
Journal cover image

Published In

Immunity

DOI

EISSN

1097-4180

Publication Date

January 24, 2013

Volume

38

Issue

1

Start / End Page

176 / 186

Location

United States

Related Subject Headings

  • Protein Conformation
  • Protein Binding
  • Peptides
  • Molecular Sequence Data
  • Molecular Docking Simulation
  • Immunology
  • Humans
  • HIV Envelope Protein gp120
  • HIV Antibodies
  • Antibodies, Monoclonal