5f96 Citations

Maturation Pathway from Germline to Broad HIV-1 Neutralizer of a CD4-Mimic Antibody.

Abstract

Antibodies with ontogenies from VH1-2 or VH1-46-germline genes dominate the broadly neutralizing response against the CD4-binding site (CD4bs) on HIV-1. Here, we define with longitudinal sampling from time-of-infection the development of a VH1-46-derived antibody lineage that matured to neutralize 90% of HIV-1 isolates. Structures of lineage antibodies CH235 (week 41 from time-of-infection, 18% breadth), CH235.9 (week 152, 77%), and CH235.12 (week 323, 90%) demonstrated the maturing epitope to focus on the conformationally invariant portion of the CD4bs. Similarities between CH235 lineage and five unrelated CD4bs lineages in epitope focusing, length-of-time to develop breadth, and extraordinary level of somatic hypermutation suggested commonalities in maturation among all CD4bs antibodies. Fortunately, the required CH235-lineage hypermutation appeared substantially guided by the intrinsic mutability of the VH1-46 gene, which closely resembled VH1-2. We integrated our CH235-lineage findings with a second broadly neutralizing lineage and HIV-1 co-evolution to suggest a vaccination strategy for inducing both lineages.

Reviews - 5f96 mentioned but not cited (1)

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Articles - 5f96 mentioned but not cited (6)

  1. Maturation Pathway from Germline to Broad HIV-1 Neutralizer of a CD4-Mimic Antibody. Bonsignori M, Zhou T, Sheng Z, Chen L, Gao F, Joyce MG, Ozorowski G, Chuang GY, Schramm CA, Wiehe K, Alam SM, Bradley T, Gladden MA, Hwang KK, Iyengar S, Kumar A, Lu X, Luo K, Mangiapani MC, Parks RJ, Song H, Acharya P, Bailer RT, Cao A, Druz A, Georgiev IS, Kwon YD, Louder MK, Zhang B, Zheng A, Hill BJ, Kong R, Soto C, NISC Comparative Sequencing Program, Mullikin JC, Douek DC, Montefiori DC, Moody MA, Shaw GM, Hahn BH, Kelsoe G, Hraber PT, Korber BT, Boyd SD, Fire AZ, Kepler TB, Shapiro L, Ward AB, Mascola JR, Liao HX, Kwong PD, Haynes BF. Cell 165 449-463 (2016)
  2. Recapitulation of HIV-1 Env-antibody coevolution in macaques leading to neutralization breadth. Roark RS, Li H, Williams WB, Chug H, Mason RD, Gorman J, Wang S, Lee FH, Rando J, Bonsignori M, Hwang KK, Saunders KO, Wiehe K, Moody MA, Hraber PT, Wagh K, Giorgi EE, Russell RM, Bibollet-Ruche F, Liu W, Connell J, Smith AG, DeVoto J, Murphy AI, Smith J, Ding W, Zhao C, Chohan N, Okumura M, Rosario C, Ding Y, Lindemuth E, Bauer AM, Bar KJ, Ambrozak D, Chao CW, Chuang GY, Geng H, Lin BC, Louder MK, Nguyen R, Zhang B, Lewis MG, Raymond DD, Doria-Rose NA, Schramm CA, Douek DC, Roederer M, Kepler TB, Kelsoe G, Mascola JR, Kwong PD, Korber BT, Harrison SC, Haynes BF, Hahn BH, Shaw GM. Science 371 eabd2638 (2021)
  3. Estimation of the breadth of CD4bs targeting HIV antibodies by molecular modeling and machine learning. Conti S, Karplus M. PLoS Comput Biol 15 e1006954 (2019)
  4. research-article Engineering immunogens that select for specific mutations in HIV broadly neutralizing antibodies. Henderson R, Anasti K, Manne K, Stalls V, Saunders C, Bililign Y, Williams A, Bubphamala P, Montani M, Kachhap S, Li J, Jaing C, Newman A, Cain D, Lu X, Venkatayogi S, Berry M, Wagh K, Korber B, Saunders KO, Tian M, Alt F, Wiehe K, Acharya P, Alam SM, Haynes BF. bioRxiv 2023.12.15.571700 (2023)
  5. research-article Microsecond dynamics control the HIV-1 envelope conformation. Bennett AL, Edwards RJ, Kosheleva I, Saunders C, Bililign Y, Williams A, Manosouri K, Saunders KO, Haynes BF, Acharya P, Henderson R. bioRxiv 2023.05.17.541130 (2023)
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Articles citing this publication (143)

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