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Displaying record number 3020

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MAb ID	CH59
HXB2 Location	gp160(169-182) DNA(6729..6770)	gp160 Epitope Map
Author Location	gp120
Epitope	KKKVHALFYKLDIV	Epitope Alignment
Ab Type	gp120 V2 // V2 glycan(V2g) // V2 apex
Neutralizing	tier 1
Species (Isotype)	human(IgG1)
Patient	347759
Immunogen	vaccine
Country	Thailand
Keywords	ADCC, antibody binding site, antibody generation, antibody lineage, review, structure, vaccine-induced immune responses

Vaccine Details

Notes

Showing 4 matching of 11 total notes.

• CH59: V2-directed antibodies isolated from the RV144 vaccine trial correlated with reduced HIV-1 infection risk by interacting with positively charged residues at positions 168, 169, and 171 in V2. Here, van Eeden et al. isolate two antibody lineages (CAP228-16H/19F and CAP228–3D), similar to RV144 Abs CH58 and CH59, from infected subject CAP228, that mediate potent antibody-dependent cell-mediated cytotoxicity (ADCC). While in both CH58 and CH59 binding was restricted to two light chain genes, the new Ab lineages isolated in this study identify a third V2-reactive light chain gene, increasing the antibody repertoire potentially elicited by vaccination. These data helped in the understanding of the development of cross-reactive, V2-binding, antiviral Abs. vanEeden2018 (ADCC, antibody binding site, antibody lineage)
• CH59: Combinations of antibodies isolated from RV144 vaccinees were shown to synergistically mediate multiple anti-HIV activities: neutralization, virus capture, and ADCC. Antibodies included CH54, CH57, CH58, CH59, CH90, HG107, and HG120. Synergy was particular notable for combinations of V2 and C1 MAbs. In particular, the ADCC activity of CH58 was increased by synergy with other monoclonal antibodies at concentrations similar to those found in RV144 vaccinees. Pollara2014 (ADCC, vaccine-induced immune responses)
• CH59: The complexity of the epitopes recognized by ADCC responses in HIV-1 infected individuals and candidate vaccine recipients is discussed in this review. RV144 vaccine induced CH59 is discussed as the V2 region-targeting, neutralizing anti-gp120 Ab exhibiting ADCC activity and having a linear epitope. CH59 bind to the same region of BNAb PG9, but do not display preferential binding to gp120 and don't bind to glycans in position 156 and 160. The recombinant version of CH59 could not capture free Tier 2 virions or neutralize Tier 2 isolates. Pollara2013 (ADCC, review)
• CH59: Four V2 MAbs CH58, CH59, HG107 and HG120 were isolated from RV144 Thai HIV-1 vaccinees. These MAbs recognized residue 169, neutralized laboratory HIV-1 (tier 1 strains) and mediated ADCC which was dependent on position 169. The K169Q mutation abrogated neutralization by CH58 and CH59. CH58 and CH59 MAbs bound to a linear peptide and the binding was glycan independent. Using the alanin scanning, the important residues were K169, H173, F176, Y177. Crystal structures revealed that CH58, CH59, and PG9 recognize overlapping V2 epitopes in dramatically different conformations, ranging from helical to beta strands. Liao2013b (ADCC, antibody generation, vaccine-induced immune responses, structure)

References

Showing 4 matching of 11 total references.

Isolation Paper
Liao2013b Hua-Xin Liao, Mattia Bonsignori, S. Munir Alam, Jason S. McLellan, Georgia D. Tomaras, M. Anthony Moody, Daniel M. Kozink, Kwan-Ki Hwang, Xi Chen, Chun-Yen Tsao, Pinghuang Liu, Xiaozhi Lu, Robert J. Parks, David C. Montefiori, Guido Ferrari, Justin Pollara, Mangala Rao, Kristina K. Peachman, Sampa Santra, Norman L. Letvin, Nicos Karasavvas, Zhi-Yong Yang, Kaifan Dai, Marie Pancera, Jason Gorman, Kevin Wiehe, Nathan I. Nicely, Supachai Rerks-Ngarm, Sorachai Nitayaphan, Jaranit Kaewkungwal, Punnee Pitisuttithum, James Tartaglia, Faruk Sinangil, Jerome H. Kim, Nelson L. Michael, Thomas B. Kepler, Peter D. Kwong, John R. Mascola, Gary J. Nabel, Abraham Pinter, Susan Zolla-Pazner, and Barton F. Haynes. Vaccine Induction of Antibodies Against a Structurally Heterogeneous Site of Immune Pressure within HIV-1 Envelope Protein Variable Regions 1 and 2. Immunity, 38(1):176-186, 24 Jan 2013. PubMed ID: 23313589. Show all entries for this paper.

Pollara2013 Justin Pollara, Mattia Bonsignori, M. Anthony Moody, Marzena Pazgier, Barton F. Haynes, and Guido Ferrari. Epitope Specificity of Human Immunodeficiency Virus-1 Antibody Dependent Cellular Cytotoxicity (ADCC) Responses. Curr. HIV Res., 11(5):378-387, Jul 2013. PubMed ID: 24191939. Show all entries for this paper.

Pollara2014 Justin Pollara, Mattia Bonsignori, M. Anthony Moody, Pinghuang Liu, S. Munir Alam, Kwan-Ki Hwang, Thaddeus C. Gurley, Daniel M. Kozink, Lawrence C. Armand, Dawn J. Marshall, John F. Whitesides, Jaranit Kaewkungwal, Sorachai Nitayaphan, Punnee Pitisuttithum, Supachai Rerks-Ngarm, Merlin L. Robb, Robert J. O'Connell, Jerome H. Kim, Nelson L. Michael, David C. Montefiori, Georgia D. Tomaras, Hua-Xin Liao, Barton F. Haynes, and Guido Ferrari. HIV-1 Vaccine-Induced C1 and V2 Env-Specific Antibodies Synergize for Increased Antiviral Activities. J. Virol., 88(14):7715-7726, Jul 2014. PubMed ID: 24807721. Show all entries for this paper.

vanEeden2018 Charmaine van Eeden, Constantinos Kurt Wibmer, Cathrine Scheepers, Simone I. Richardson, Molati Nonyane, Bronwen Lambson, Nonhlanhla N. Mkhize, Balakrishnan Vijayakumar, Zizhang Sheng, Sherry Stanfield-Oakley, Jinal N. Bhiman, Valerie Bekker, Tandile Hermanus, Batsirai Mabvakure, Arshad Ismail, M. Anthony Moody, Kevin Wiehe, Nigel Garrett, Salim Abdool Karim, Heini Dirr, Manuel A. Fernandes, Yasien Sayed, Lawrence Shapiro, Guido Ferrari, Barton F. Haynes, Penny L. Moore, and Lynn Morris. V2-Directed Vaccine-Like Antibodies from HIV-1 Infection Identify an Additional K169-Binding Light Chain Motif with Broad ADCC Activity. Cell Rep., 25(11):3123-3135.e6, 11 Dec 2018. PubMed ID: 30540944. Show all entries for this paper.