@article{Juraska2024a,
abstract = {In the Antibody Mediated Prevention (AMP) trials (HVTN 704/HPTN 085 and HVTN 703/HPTN 081), prevention efficacy (PE) of the monoclonal broadly neutralizing antibody (bnAb) VRC01 (vs. placebo) against HIV-1 acquisition diagnosis varied according to the HIV-1 Envelope (Env) neutralization sensitivity to VRC01, as measured by 80{\%} inhibitory concentration (IC80). Here, we performed a genotypic sieve analysis, a complementary approach to gaining insight into correlates of protection that assesses how PE varies with HIV-1 sequence features. We analyzed HIV-1 Env amino acid (AA) sequences from the earliest available HIV-1 RNA-positive plasma samples from AMP participants diagnosed with HIV-1 and identified Env sequence features that associated with PE. The strongest Env AA sequence correlate in both trials was VRC01 epitope distance that quantifies the divergence of the VRC01 epitope in an acquired HIV-1 isolate from the VRC01 epitope of reference HIV-1 strains that were most sensitive to VRC01-mediated neutralization. In HVTN 704/HPTN 085, the Env sequence-based predicted probability that VRC01 IC80 against the acquired isolate exceeded 1 µg/mL also significantly associated with PE. In HVTN 703/HPTN 081, a physicochemical-weighted Hamming distance across 50 VRC01 binding-associated Env AA positions of the acquired isolate from the most VRC01-sensitive HIV-1 strain significantly associated with PE. These results suggest that incorporating mutation scoring by BLOSUM62 and weighting by the strength of interactions at AA positions in the epitope:VRC01 interface can optimize performance of an Env sequence-based biomarker of VRC01 prevention efficacy. Future work could determine whether these results extend to other bnAbs and bnAb combinations.},
author = {Juraska, Michal and Bai, Hongjun and DeCamp, Allan C and Magaret, Craig A and Li, Li and Gillespie, Kevin and Carpp, Lindsay N and Giorgi, Elena E and Ludwig, James and Molitor, Cindy and Hudson, Aaron and Williamson, Brian D and Espy, Nicole and Simpkins, Brian and Rudnicki, Erika and Shao, Danica and Rossenkhan, Raabya and Edlefsen, Paul T and Westfall, Dylan H and Deng, Wenjie and Chen, Lennie and Zhao, Hong and Bhattacharya, Tanmoy and Pankow, Alec and Murrell, Ben and Yssel, Anna and Matten, David and York, Talita and Beaume, Nicolas and Gwashu-Nyangiwe, Asanda and Ndabambi, Nonkululeko and Thebus, Ruwayhida and Karuna, Shelly T and Morris, Lynn and Montefiori, David C and Hural, John A and Cohen, Myron S and Corey, Lawrence and Rolland, Morgane and Gilbert, Peter B and Williamson, Carolyn and Mullins, James I},
doi = {10.1073/PNAS.2308942121/SUPPL_FILE/PNAS.2308942121.SD01.CSV},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Juraska et al. - 2024 - Prevention efficacy of the broadly neutralizing antibody VRC01 depends on HIV-1 envelope sequence features.pdf:pdf},
issn = {10916490},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
keywords = {HIV diversity,Hamming distance,OA,PAR score,epitope,fund{\_}not{\_}ack,original,sieve analysis},
mendeley-tags = {OA,fund{\_}not{\_}ack,original},
month = {jan},
number = {4},
pages = {e2308942121},
pmid = {38241441},
publisher = {National Academy of Sciences},
title = {{Prevention efficacy of the broadly neutralizing antibody VRC01 depends on HIV-1 envelope sequence features}},
url = {https://www.pnas.org/doi/abs/10.1073/pnas.2308942121},
volume = {121},
year = {2024}
}

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I"],"bibdata":{"bibtype":"article","type":"article","abstract":"In the Antibody Mediated Prevention (AMP) trials (HVTN 704/HPTN 085 and HVTN 703/HPTN 081), prevention efficacy (PE) of the monoclonal broadly neutralizing antibody (bnAb) VRC01 (vs. placebo) against HIV-1 acquisition diagnosis varied according to the HIV-1 Envelope (Env) neutralization sensitivity to VRC01, as measured by 80% inhibitory concentration (IC80). Here, we performed a genotypic sieve analysis, a complementary approach to gaining insight into correlates of protection that assesses how PE varies with HIV-1 sequence features. We analyzed HIV-1 Env amino acid (AA) sequences from the earliest available HIV-1 RNA-positive plasma samples from AMP participants diagnosed with HIV-1 and identified Env sequence features that associated with PE. The strongest Env AA sequence correlate in both trials was VRC01 epitope distance that quantifies the divergence of the VRC01 epitope in an acquired HIV-1 isolate from the VRC01 epitope of reference HIV-1 strains that were most sensitive to VRC01-mediated neutralization. In HVTN 704/HPTN 085, the Env sequence-based predicted probability that VRC01 IC80 against the acquired isolate exceeded 1 µg/mL also significantly associated with PE. In HVTN 703/HPTN 081, a physicochemical-weighted Hamming distance across 50 VRC01 binding-associated Env AA positions of the acquired isolate from the most VRC01-sensitive HIV-1 strain significantly associated with PE. These results suggest that incorporating mutation scoring by BLOSUM62 and weighting by the strength of interactions at AA positions in the epitope:VRC01 interface can optimize performance of an Env sequence-based biomarker of VRC01 prevention efficacy. Future work could determine whether these results extend to other bnAbs and bnAb combinations.","author":[{"propositions":[],"lastnames":["Juraska"],"firstnames":["Michal"],"suffixes":[]},{"propositions":[],"lastnames":["Bai"],"firstnames":["Hongjun"],"suffixes":[]},{"propositions":[],"lastnames":["DeCamp"],"firstnames":["Allan","C"],"suffixes":[]},{"propositions":[],"lastnames":["Magaret"],"firstnames":["Craig","A"],"suffixes":[]},{"propositions":[],"lastnames":["Li"],"firstnames":["Li"],"suffixes":[]},{"propositions":[],"lastnames":["Gillespie"],"firstnames":["Kevin"],"suffixes":[]},{"propositions":[],"lastnames":["Carpp"],"firstnames":["Lindsay","N"],"suffixes":[]},{"propositions":[],"lastnames":["Giorgi"],"firstnames":["Elena","E"],"suffixes":[]},{"propositions":[],"lastnames":["Ludwig"],"firstnames":["James"],"suffixes":[]},{"propositions":[],"lastnames":["Molitor"],"firstnames":["Cindy"],"suffixes":[]},{"propositions":[],"lastnames":["Hudson"],"firstnames":["Aaron"],"suffixes":[]},{"propositions":[],"lastnames":["Williamson"],"firstnames":["Brian","D"],"suffixes":[]},{"propositions":[],"lastnames":["Espy"],"firstnames":["Nicole"],"suffixes":[]},{"propositions":[],"lastnames":["Simpkins"],"firstnames":["Brian"],"suffixes":[]},{"propositions":[],"lastnames":["Rudnicki"],"firstnames":["Erika"],"suffixes":[]},{"propositions":[],"lastnames":["Shao"],"firstnames":["Danica"],"suffixes":[]},{"propositions":[],"lastnames":["Rossenkhan"],"firstnames":["Raabya"],"suffixes":[]},{"propositions":[],"lastnames":["Edlefsen"],"firstnames":["Paul","T"],"suffixes":[]},{"propositions":[],"lastnames":["Westfall"],"firstnames":["Dylan","H"],"suffixes":[]},{"propositions":[],"lastnames":["Deng"],"firstnames":["Wenjie"],"suffixes":[]},{"propositions":[],"lastnames":["Chen"],"firstnames":["Lennie"],"suffixes":[]},{"propositions":[],"lastnames":["Zhao"],"firstnames":["Hong"],"suffixes":[]},{"propositions":[],"lastnames":["Bhattacharya"],"firstnames":["Tanmoy"],"suffixes":[]},{"propositions":[],"lastnames":["Pankow"],"firstnames":["Alec"],"suffixes":[]},{"propositions":[],"lastnames":["Murrell"],"firstnames":["Ben"],"suffixes":[]},{"propositions":[],"lastnames":["Yssel"],"firstnames":["Anna"],"suffixes":[]},{"propositions":[],"lastnames":["Matten"],"firstnames":["David"],"suffixes":[]},{"propositions":[],"lastnames":["York"],"firstnames":["Talita"],"suffixes":[]},{"propositions":[],"lastnames":["Beaume"],"firstnames":["Nicolas"],"suffixes":[]},{"propositions":[],"lastnames":["Gwashu-Nyangiwe"],"firstnames":["Asanda"],"suffixes":[]},{"propositions":[],"lastnames":["Ndabambi"],"firstnames":["Nonkululeko"],"suffixes":[]},{"propositions":[],"lastnames":["Thebus"],"firstnames":["Ruwayhida"],"suffixes":[]},{"propositions":[],"lastnames":["Karuna"],"firstnames":["Shelly","T"],"suffixes":[]},{"propositions":[],"lastnames":["Morris"],"firstnames":["Lynn"],"suffixes":[]},{"propositions":[],"lastnames":["Montefiori"],"firstnames":["David","C"],"suffixes":[]},{"propositions":[],"lastnames":["Hural"],"firstnames":["John","A"],"suffixes":[]},{"propositions":[],"lastnames":["Cohen"],"firstnames":["Myron","S"],"suffixes":[]},{"propositions":[],"lastnames":["Corey"],"firstnames":["Lawrence"],"suffixes":[]},{"propositions":[],"lastnames":["Rolland"],"firstnames":["Morgane"],"suffixes":[]},{"propositions":[],"lastnames":["Gilbert"],"firstnames":["Peter","B"],"suffixes":[]},{"propositions":[],"lastnames":["Williamson"],"firstnames":["Carolyn"],"suffixes":[]},{"propositions":[],"lastnames":["Mullins"],"firstnames":["James","I"],"suffixes":[]}],"doi":"10.1073/PNAS.2308942121/SUPPL_FILE/PNAS.2308942121.SD01.CSV","file":":C$\\$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Juraska et al. - 2024 - Prevention efficacy of the broadly neutralizing antibody VRC01 depends on HIV-1 envelope sequence features.pdf:pdf","issn":"10916490","journal":"Proceedings of the National Academy of Sciences of the United States of America","keywords":"HIV diversity,Hamming distance,OA,PAR score,epitope,fund_not_ack,original,sieve analysis","mendeley-tags":"OA,fund_not_ack,original","month":"jan","number":"4","pages":"e2308942121","pmid":"38241441","publisher":"National Academy of Sciences","title":"Prevention efficacy of the broadly neutralizing antibody VRC01 depends on HIV-1 envelope sequence features","url":"https://www.pnas.org/doi/abs/10.1073/pnas.2308942121","volume":"121","year":"2024","bibtex":"@article{Juraska2024a,\r\nabstract = {In the Antibody Mediated Prevention (AMP) trials (HVTN 704/HPTN 085 and HVTN 703/HPTN 081), prevention efficacy (PE) of the monoclonal broadly neutralizing antibody (bnAb) VRC01 (vs. placebo) against HIV-1 acquisition diagnosis varied according to the HIV-1 Envelope (Env) neutralization sensitivity to VRC01, as measured by 80{\\%} inhibitory concentration (IC80). 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