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Optimal Combinations of Broadly Neutralizing Antibodies for Prevention and Treatment of HIV-1 Clade C Infection.

Publication ,  Journal Article
Wagh, K; Bhattacharya, T; Williamson, C; Robles, A; Bayne, M; Garrity, J; Rist, M; Rademeyer, C; Yoon, H; Lapedes, A; Gao, H; Greene, K ...
Published in: PLoS Pathog
March 2016

The identification of a new generation of potent broadly neutralizing HIV-1 antibodies (bnAbs) has generated substantial interest in their potential use for the prevention and/or treatment of HIV-1 infection. While combinations of bnAbs targeting distinct epitopes on the viral envelope (Env) will likely be required to overcome the extraordinary diversity of HIV-1, a key outstanding question is which bnAbs, and how many, will be needed to achieve optimal clinical benefit. We assessed the neutralizing activity of 15 bnAbs targeting four distinct epitopes of Env, including the CD4-binding site (CD4bs), the V1/V2-glycan region, the V3-glycan region, and the gp41 membrane proximal external region (MPER), against a panel of 200 acute/early clade C HIV-1 Env pseudoviruses. A mathematical model was developed that predicted neutralization by a subset of experimentally evaluated bnAb combinations with high accuracy. Using this model, we performed a comprehensive and systematic comparison of the predicted neutralizing activity of over 1,600 possible double, triple, and quadruple bnAb combinations. The most promising bnAb combinations were identified based not only on breadth and potency of neutralization, but also other relevant measures, such as the extent of complete neutralization and instantaneous inhibitory potential (IIP). By this set of criteria, triple and quadruple combinations of bnAbs were identified that were significantly more effective than the best double combinations, and further improved the probability of having multiple bnAbs simultaneously active against a given virus, a requirement that may be critical for countering escape in vivo. These results provide a rationale for advancing bnAb combinations with the best in vitro predictors of success into clinical trials for both the prevention and treatment of HIV-1 infection.

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Published In

PLoS Pathog

DOI

EISSN

1553-7374

Publication Date

March 2016

Volume

12

Issue

3

Start / End Page

e1005520

Location

United States

Related Subject Headings

  • Virology
  • Humans
  • HIV-1
  • HIV Infections
  • HIV Antibodies
  • Epitopes
  • Antibodies, Neutralizing
  • 3207 Medical microbiology
  • 3204 Immunology
  • 3107 Microbiology
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Wagh, K., Bhattacharya, T., Williamson, C., Robles, A., Bayne, M., Garrity, J., … Seaman, M. S. (2016). Optimal Combinations of Broadly Neutralizing Antibodies for Prevention and Treatment of HIV-1 Clade C Infection. PLoS Pathog, 12(3), e1005520. https://doi.org/10.1371/journal.ppat.1005520
Wagh, Kshitij, Tanmoy Bhattacharya, Carolyn Williamson, Alex Robles, Madeleine Bayne, Jetta Garrity, Michael Rist, et al. “Optimal Combinations of Broadly Neutralizing Antibodies for Prevention and Treatment of HIV-1 Clade C Infection.PLoS Pathog 12, no. 3 (March 2016): e1005520. https://doi.org/10.1371/journal.ppat.1005520.
Wagh K, Bhattacharya T, Williamson C, Robles A, Bayne M, Garrity J, et al. Optimal Combinations of Broadly Neutralizing Antibodies for Prevention and Treatment of HIV-1 Clade C Infection. PLoS Pathog. 2016 Mar;12(3):e1005520.
Wagh, Kshitij, et al. “Optimal Combinations of Broadly Neutralizing Antibodies for Prevention and Treatment of HIV-1 Clade C Infection.PLoS Pathog, vol. 12, no. 3, Mar. 2016, p. e1005520. Pubmed, doi:10.1371/journal.ppat.1005520.
Wagh K, Bhattacharya T, Williamson C, Robles A, Bayne M, Garrity J, Rist M, Rademeyer C, Yoon H, Lapedes A, Gao H, Greene K, Louder MK, Kong R, Karim SA, Burton DR, Barouch DH, Nussenzweig MC, Mascola JR, Morris L, Montefiori DC, Korber B, Seaman MS. Optimal Combinations of Broadly Neutralizing Antibodies for Prevention and Treatment of HIV-1 Clade C Infection. PLoS Pathog. 2016 Mar;12(3):e1005520.

Published In

PLoS Pathog

DOI

EISSN

1553-7374

Publication Date

March 2016

Volume

12

Issue

3

Start / End Page

e1005520

Location

United States

Related Subject Headings

  • Virology
  • Humans
  • HIV-1
  • HIV Infections
  • HIV Antibodies
  • Epitopes
  • Antibodies, Neutralizing
  • 3207 Medical microbiology
  • 3204 Immunology
  • 3107 Microbiology