VRC01 exerted differential pressure on HIV-1 Env from subtypes B and C that continued in the first weeks post-diagnosis in the AMP trials.
Обработка статьи · этапы, ошибки и управление
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Bai Hongjun, Juraska Michal, Magaret Craig A, Yssel Anna, Rossenkhan Raabya, Murrell Ben, Dearlove Bethany L, Lewitus Eric, deCamp Allan C, Giorgi Elena E, Ludwig James, Westfall Dylan H, Deng Wenjie, Chen Lennie, Zhao Hong, Pankow Alec, Bhattacharya Tanmoy, York Talita, Gwashu-Nyangiwe Asanda, Ndabambi Nonkululeko, Thebus Ruwayhida, Ake Julie A, Vasan Sandhya, Randhawa April, Hural John A, Edupuganti Sri, Mgodi Nyaradzo, Karuna Shelly T, Morris Lynn, Montefiori David C, Cohen Myron S, Corey Lawrence, Edlefsen Paul T, McElrath M Julianna, Gilbert Peter B, Williamson Carolyn, Mullins James I, Rolland Morgane
Аннотация
METHODS: We calculated VRC01 epitope distances (a 3D structure informed measure of how the VRC01 epitope in a sequence differs from that epitope in known VRC01 sensitive strains) to compare >35,000 Envelopes sampled from 172 participants with mostly subtype C viruses in HVTN 703 and subtype B in HVTN 704.
RESULTS: At the first visit with detectable HIV-1, we found fewer distinct VRC01 epitopes in the sequences from participants in the VRC01 high-dose group in HVTN 704 (p=0.054), suggesting that some epitope variants were blocked in these participants who harbored subtype B viruses. In both trials, VRC01 epitope distances were significantly larger in the VRC01 high-dose groups than in the placebo groups (p≤0.010). Moreover, sequences sampled in the first month after diagnosis showed that the rate of change in VRC01 epitope distances was significantly higher in the VRC01 groups than in the placebo in the HVTN 703 trial (p≤0.036).
CONCLUSIONS: These findings show the impact of sieve acquisition (variants blocked among subtype B viruses) and post-acquisition (stronger impact of VRC01-mediated escape in subtype C) effects, highlighting a complex intersection between HIV-1 subtypes, escape pathways and antibody-mediated prevention. The differential pressure exerted by VRC01 on subtype B vs. C viruses emphasizes that escape pathways need to be considered when selecting bnAbs for clinical trials.