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MAb ID	CH247
HXB2 Location	gp160	gp160 Epitope Map
Author Location	Env( P)
Epitope
Ab Type	gp120 V2-CD4BS
Neutralizing
Species (Isotype)	human(IgG1)
Patient	Donor CH505
Immunogen	HIV-1 infection
Keywords	antibody generation, antibody lineage, antibody sequence, neutralization, review

Notes

Showing 2 of 2 notes.

CH247: This review discussed antibody-virus coevolution and lineage development as a path to elicit broadly neutralizing Abs. CD4bs mAbs from donor CH505 (lineages CH103 and CH235) were used as main examples. Bonsignori2017a (review, antibody lineage)
CH247: In 5 years additional members of the CH235 clonal lineage were isolated based on deep sequencing of donor CH505's V_L and V_H chains at 17 timepoints in the donor's infection. Two of these had greater neutralization potency, CH235.9 and CH235.12. Study of crystal structures indicated a site of vulnerability near the Env CD4 binding site. The lineages of CH103 and CH235, both derived from Donor CH505 were compared - CH103 lineage K_d increased an order of magnitude each step of maturation but maintained a fast association rate; CH235 lineage however, had slower K_ds and K_as over maturation. CH247 neutralized 100% of a 113-patient CH505-derived autologous pseudoviral panel as part of CH103 lineages, at potencies of <50 µg/ml. Bonsignori2016 (antibody generation, neutralization, antibody sequence, antibody lineage)

References

Showing 2 of 2 references.

Isolation Paper
Bonsignori2016 Mattia Bonsignori, Tongqing Zhou, Zizhang Sheng, Lei Chen, Feng Gao, M. Gordon Joyce, Gabriel Ozorowski, Gwo-Yu Chuang, Chaim A. Schramm, Kevin Wiehe, S. Munir Alam, Todd Bradley, Morgan A. Gladden, Kwan-Ki Hwang, Sheelah Iyengar, Amit Kumar, Xiaozhi Lu, Kan Luo, Michael C. Mangiapani, Robert J. Parks, Hongshuo Song, Priyamvada Acharya, Robert T. Bailer, Allen Cao, Aliaksandr Druz, Ivelin S. Georgiev, Young D. Kwon, Mark K. Louder, Baoshan Zhang, Anqi Zheng, Brenna J. Hill, Rui Kong, Cinque Soto, NISC Comparative Sequencing Program, James C. Mullikin, Daniel C. Douek, David C. Montefiori, Michael A. Moody, George M. Shaw, Beatrice H. Hahn, Garnett Kelsoe, Peter T. Hraber, Bette T. Korber, Scott D. Boyd, Andrew Z. Fire, Thomas B. Kepler, Lawrence Shapiro, Andrew B. Ward, John R. Mascola, Hua-Xin Liao, Peter D. Kwong, and Barton F. Haynes. Maturation Pathway from Germline to Broad HIV-1 Neutralizer of a CD4-Mimic Antibody. Cell, 165(2):449-463, 7 Apr 2016. PubMed ID: 26949186. Show all entries for this paper.

Bonsignori2017a Mattia Bonsignori, Hua-Xin Liao, Feng Gao, Wilton B. Williams, S. Munir Alam, David C. Montefiori, and Barton F. Haynes. Antibody-Virus Co-evolution in HIV Infection: Paths for HIV Vaccine Development. Immunol. Rev., 275(1):145-160, Jan 2017. PubMed ID: 28133802. Show all entries for this paper.