Early Antibody Lineage Diversification and Independent Limb Maturation Lead to Broad HIV-1 Neutralization Targeting the Env High-Mannose Patch
作者： Daniel T. MacLeod , Nancy M. Choi , Bryan Briney , Fernando Garces , Lorena S. Ver
DOI: 10.1016/J.IMMUNI.2016.04.016
关键词:
摘要: The high-mannose patch on HIV Env is a preferred target for broadly neutralizing antibodies (bnAbs), but to date, no vaccination regimen has elicited bnAbs against this region. Here, we present the development of bnAb lineage targeting in an HIV-1 subtype-C-infected donor from sub-Saharan Africa. Abs first acquired autologous neutralization, then gradually matured achieve breadth. One Ab neutralized >47% strains with only ∼11% somatic hypermutation and insertions or deletions. By sequencing env, determined key residues that triggered participated Ab-Env coevolution. Next-generation repertoire showed early expansive diversification followed by independent maturation individual limbs, several them developing notable breadth potency. Overall, findings are encouraging vaccine standpoint suggest immunization strategies mimicking evolution entire promoting multiple diverse pathways.
rcsb.org参考文章(53)
M Spellerberg, F K Stevenson, J D Capra, K Victor, V Pascual, T J Hamblin, VH restriction among human cold agglutinins. The VH4-21 gene segment is required to encode anti-I and anti-i specificities. Journal of Immunology. ,vol. 149, pp. 2337- 2344 ,(1992)
Zbyszek Otwinowski, Wladek Minor, Processing of X-ray diffraction data collected in oscillation mode Methods in Enzymology. ,vol. 276, pp. 307- 326 ,(1997) , 10.1016/S0076-6879(97)76066-X
M B Spellerberg, D Lelsz, I Randen, F K Stevenson, J D Capra, K Victor, K M Thompson, V Pascual, J Natvig, T J Hamblin, Nucleotide sequence analysis of the V regions of two IgM cold agglutinins. Evidence that the VH4-21 gene segment is responsible for the major cross-reactive idiotype. Journal of Immunology. ,vol. 146, pp. 4385- 4391 ,(1991)
Barton F Haynes, Garnett Kelsoe, Stephen C Harrison, Thomas B Kepler, B-cell–lineage immunogen design in vaccine development with HIV-1 as a case study Nature Biotechnology. ,vol. 30, pp. 423- 433 ,(2012) , 10.1038/NBT.2197
Dennis R Burton, Rafi Ahmed, Dan H Barouch, Salvatore T Butera, Shane Crotty, Adam Godzik, Daniel E Kaufmann, M Juliana McElrath, Michel C Nussenzweig, Bali Pulendran, Chris N Scanlan, William R Schief, Guido Silvestri, Hendrik Streeck, Bruce D Walker, Laura M Walker, Andrew B Ward, Ian A Wilson, Richard Wyatt, None, A Blueprint for HIV Vaccine Discovery Cell Host & Microbe. ,vol. 12, pp. 396- 407 ,(2012) , 10.1016/J.CHOM.2012.09.008
H. Mouquet, L. Scharf, Z. Euler, Y. Liu, C. Eden, J. F. Scheid, A. Halper-Stromberg, P. N. P. Gnanapragasam, D. I. R. Spencer, M. S. Seaman, H. Schuitemaker, T. Feizi, M. C. Nussenzweig, P. J. Bjorkman, Complex-type N-glycan recognition by potent broadly neutralizing HIV antibodies. Proceedings of the National Academy of Sciences of the United States of America. ,vol. 109, pp. 19059- 19060 ,(2012) , 10.1073/PNAS.1217207109
Hua-Xin Liao, , Rebecca Lynch, Tongqing Zhou, Feng Gao, S. Munir Alam, Scott D. Boyd, Andrew Z. Fire, Krishna M. Roskin, Chaim A. Schramm, Zhenhai Zhang, Jiang Zhu, Lawrence Shapiro, James C. Mullikin, S. Gnanakaran, Peter Hraber, Kevin Wiehe, Garnett Kelsoe, Guang Yang, Shi-Mao Xia, David C. Montefiori, Robert Parks, Krissey E. Lloyd, Richard M. Scearce, Kelly A. Soderberg, Myron Cohen, Gift Kamanga, Mark K. Louder, Lillian M. Tran, Yue Chen, Fangping Cai, Sheri Chen, Stephanie Moquin, Xiulian Du, M. Gordon Joyce, Sanjay Srivatsan, Baoshan Zhang, Anqi Zheng, George M. Shaw, Beatrice H. Hahn, Thomas B. Kepler, Bette T. M. Korber, Peter D. Kwong, John R. Mascola, Barton F. Haynes, Co-evolution of a broadly neutralizing HIV-1 antibody and founder virus Nature. ,vol. 496, pp. 469- 476 ,(2013) , 10.1038/NATURE12053
Bryan S. Briney, Jordan R. Willis, James E. Crowe, Human Peripheral Blood Antibodies with Long HCDR3s Are Established Primarily at Original Recombination Using a Limited Subset of Germline Genes PLoS ONE. ,vol. 7, pp. e36750- ,(2012) , 10.1371/JOURNAL.PONE.0036750
Mengfei Liu, Guang Yang, Kevin Wiehe, Nathan I. Nicely, Nathan A. Vandergrift, Wes Rountree, Mattia Bonsignori, S. Munir Alam, Jingyun Gao, Barton F. Haynes, Garnett Kelsoe, Polyreactivity and Autoreactivity among HIV-1 Antibodies Journal of Virology. ,vol. 89, pp. 784- 798 ,(2015) , 10.1128/JVI.02378-14
Nancy S. Longo, Rebecca M. Lynch, Kevin O. Saunders, Cinque Soto, Sanjay Srivatsan, Yongping Yang, Robert T. Bailer, Mark K. Louder, James C. Mullikin, Mark Connors, Peter D. Kwong, John R. Mascola, Lawrence Shapiro, Betty Benjamin, Robert Blakesley, Gerry Bouffard, Shelise Brooks, Holly Coleman, Mila Dekhtyar, Michael Gregory, Xiaobin Guan, Jyoti Gupta, Joel Han, April Hargrove, Shi-ling Ho, Richelle Legaspi, Quino Maduro, Cathy Masiello, Baishali Maskeri, Jenny McDowell, Casandra Montemayor, Morgan Park, Nancy Riebow, Karen Schandler, Brian Schmidt, Christina Sison, Mal Stantripop, James Thomas, Pam Thomas, Meg Vemulapalli, Alice Young, Xueling Wu, Zhenhai Zhang, Chaim A. Schramm, M. Gordon Joyce, Young Do Kwon, Tongqing Zhou, Zizhang Sheng, Baoshan Zhang, Sijy O’Dell, Krisha McKee, Ivelin S. Georgiev, Gwo-Yu Chuang, Maturation and Diversity of the VRC01-Antibody Lineage over 15 Years of Chronic HIV-1 Infection. Cell. ,vol. 161, pp. 470- 485 ,(2015) , 10.1016/J.CELL.2015.03.004