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<p>In the antibody mediated prevention (AMP) trials, the broadly neutralizing antibody (bNAb) VRC01 demonstrated protective efficacy against susceptible HIV strains. To understand how VRC01 shaped breakthrough infections, deep sequencing was performed on 172 participants (&gt;100,000 <i>gag-Δpol</i> and <i>rev-env-Δnef</i> sequences), at diagnosis and over time, in the placebo and treatment arms of the African (HVTN703/HPTN081; NCT02568215) and Americas/Europe (HVTN704/HPTN085; NCT02716675) cohorts. A high frequency of multilineage infections was detected (38%), including co-infection with both VRC01 sensitive and resistant viruses. This high frequency is largely accounted for by low-abundance lineages. Although VRC01 does not significantly affect the genetic transmission bottleneck compared to placebo, higher VRC01 doses trend towards greater VRC01 neutralization differences among co-infecting lineages. Two-thirds of multilineage infections showed evidence of recombination at the diagnostic timepoint. In the treatment group there is evidence of recombinant viruses preferentially inheriting resistance-associated mutations. This study provides critical insights into viral genetic and antigenic diversity that needs to be targeted to achieve protection, and highlights the role of recombination in facilitating escape.</p>

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Influence of the broadly neutralizing antibody VRC01 on HIV breakthrough virus populations in antibody-mediated prevention trials

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年4月3日

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  • Carolyn Williamson,
  • Chivonne Moodley,
  • Craig A. Magaret,
  • Elena E. Giorgi,
  • Morgane Rolland,
  • Dylan H. Westfall,
  • Anna Yssel,
  • Wenjie Deng,
  • Raabya Rossenkhan,
  • Nonhlanhla N. Mkhize,
  • Lennie Chen,
  • Hong Zhao,
  • Tanmoy Bhattacharya,
  • Alec Pankow,
  • Ben Murrell,
  • Talita York,
  • Asanda Gwashu-Nyangiwe,
  • Nonkululeko Ndabambi,
  • Ruwayhida Thebus,
  • Paula Cohen,
  • Bronwen Lambson,
  • Haajira Kaldine,
  • Sinethemba Bhebhe,
  • Michal Juraska,
  • Hongjun Bai,
  • Allan C. deCamp,
  • Maurine D. Miner,
  • James Ludwig,
  • Cindy Molitor,
  • Nicolas Beaume,
  • David Matten,
  • Yunda Huang,
  • Lily Zhang,
  • Daniel B. Reeves,
  • Bryan Mayer,
  • Shelly T. Karuna,
  • John A. Hural,
  • Lynn Morris,
  • David Montefiori,
  • Roger E. Bumgarner,
  • Penny L. Moore,
  • Paul T. Edlefsen,
  • Srilatha Edupuganti,
  • Nyaradzo Mgodi,
  • M. Juliana McElrath,
  • Myron S. Cohen,
  • Lawrence Corey,
  • Peter B. Gilbert,
  • James I. Mullins

摘要

In the antibody mediated prevention (AMP) trials, the broadly neutralizing antibody (bNAb) VRC01 demonstrated protective efficacy against susceptible HIV strains. To understand how VRC01 shaped breakthrough infections, deep sequencing was performed on 172 participants (>100,000 gag-Δpol and rev-env-Δnef sequences), at diagnosis and over time, in the placebo and treatment arms of the African (HVTN703/HPTN081; NCT02568215) and Americas/Europe (HVTN704/HPTN085; NCT02716675) cohorts. A high frequency of multilineage infections was detected (38%), including co-infection with both VRC01 sensitive and resistant viruses. This high frequency is largely accounted for by low-abundance lineages. Although VRC01 does not significantly affect the genetic transmission bottleneck compared to placebo, higher VRC01 doses trend towards greater VRC01 neutralization differences among co-infecting lineages. Two-thirds of multilineage infections showed evidence of recombination at the diagnostic timepoint. In the treatment group there is evidence of recombinant viruses preferentially inheriting resistance-associated mutations. This study provides critical insights into viral genetic and antigenic diversity that needs to be targeted to achieve protection, and highlights the role of recombination in facilitating escape.