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Vaccine Details

Notes

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• ch57: Protection by mAbs was tested in two models of mucosal HIV-1 transmission. Broadly neutralizing Abs (CH31, b12), but not non-neutralizing Abs (CH29, CH38, CH54, CH57, CH90, CH58, HG129, HG130, 7b2, CH65) were able to block HIV infection in human vaginal explants. Infusion of CH31, but not CH54 or CH38, protected rhesus macaques against SHIV challenge. Astronomo2016 (immunoprophylaxis)
• CH57: 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)
• CH57: The ED motif in Λ3-SC4 light chain of neutralizing antibody CH57 demonstrated K169-dependent binding to the V2 region of HIV-1 Env (LRDKKQKVHALFYKLDIVPIED), across phylogeny (humans and macaques). K169 is the site of immune pressure in the RV144 vaccine. Wiehe2014 (neutralization, vaccine-induced immune responses)
• CH57: A highly conserved mechanism of exposure of ADCC epitopes on Env is reported, showing that binding of Env and CD4 within the same HIV-1 infected cell effectively exposes these epitopes. The mechanism might explain the evolutionary advantage of downregulation of cell surface CD4v by the Vpu and Nef proteins. CH57 was used as Fab A32 and A32 blockable RV144 MAb. Veillette2014 (ADCC)
• CH57: Plasma IgA and monomeric IgA monoclonal antibodies from RV144 vaccine recipients were examined to test the hypothesis that some fraction of the vaccine-elicited IgA response could block IgG-mediated ADCC function. CH38 and CH57 mAbs were generated from the same RV144 vaccinee. CH38 IgA2 mAb significantly inhibited ADCC mediated by RV144 CH54, CH57, CH81, and CH90 mAbs in a dose-dependent manner. Tomaras2013 (ADCC, vaccine-induced immune responses)
• CH57: The complexity of the epitopes recognized by ADCC responses in HIV-1 infected individuals and candidate vaccine recipients is discussed in this review. CH57 is discussed as the CD4i C1 region-targeting, non-neutralizing anti-gp120 mAb exhibiting ADCC activity and having a discontinuous epitope. Pollara2013 (ADCC, review)
• CH57: 23 ADCC-mediating MAbs induced by AVAC-HIV/AIDSVAX B/E vacine were isolated from 6 vaccine recipients. All donors had negative serology for HIV-1. The MAbs were modestly somatically mutated and preferentially used VH1 gene segment. 19 MAbs, including MAb CH57, were directed against conformational MAb A32-blockable gp120 epitopes. MAb CH57 was isolated from Subject 347759. Bonsignori2012a (ADCC, antibody generation, antibody sequence)

References

Showing 7 of 7 references.

Isolation Paper
Bonsignori2012a Mattia Bonsignori, Justin Pollara, M. Anthony Moody, Michael D. Alpert, Xi Chen, Kwan-Ki Hwang, Peter B. Gilbert, Ying Huang, Thaddeus C. Gurley, Daniel M. Kozink, Dawn J. Marshall, John F. Whitesides, Chun-Yen Tsao, Jaranit Kaewkungwal, Sorachai Nitayaphan, Punnee Pitisuttithum, Supachai Rerks-Ngarm, Jerome H. Kim, Nelson L. Michael, Georgia D. Tomaras, David C. Montefiori, George K. Lewis, Anthony DeVico, David T. Evans, Guido Ferrari, Hua-Xin Liao, and Barton F. Haynes. Antibody-Dependent Cellular Cytotoxicity-Mediating Antibodies from an HIV-1 Vaccine Efficacy Trial Target Multiple Epitopes and Preferentially Use the VH1 Gene Family. J. Virol., 86(21):11521-11532, Nov 2012. PubMed ID: 22896626. 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.

Tomaras2013 Georgia D. Tomaras, Guido Ferrari, Xiaoying Shen, S. Munir Alam, Hua-Xin Liao, Justin Pollara, Mattia Bonsignori, M. Anthony Moody, Youyi Fong, Xi Chen, Brigid Poling, Cindo O. Nicholson, Ruijun Zhang, Xiaozhi Lu, Robert Parks, Jaranit Kaewkungwal, Sorachai Nitayaphan, Punnee Pitisuttithum, Supachai Rerks-Ngarm, Peter B. Gilbert, Jerome H. Kim, Nelson L. Michael, David C. Montefiori, and Barton F. Haynes. Vaccine-Induced Plasma IgA Specific for the C1 Region of the HIV-1 Envelope Blocks Binding and Effector Function of IgG. Proc. Natl. Acad. Sci. U.S.A., 110(22):9019-9024, 28 May 2013. PubMed ID: 23661056. Show all entries for this paper.

Veillette2014 Maxime Veillette, Anik Désormeaux, Halima Medjahed, Nour-Elhouda Gharsallah, Mathieu Coutu, Joshua Baalwa, Yongjun Guan, George Lewis, Guido Ferrari, Beatrice H. Hahn, Barton F. Haynes, James E. Robinson, Daniel E. Kaufmann, Mattia Bonsignori, Joseph Sodroski, and Andres Finzi. Interaction with Cellular CD4 Exposes HIV-1 Envelope Epitopes Targeted by Antibody-Dependent Cell-Mediated Cytotoxicity. J. Virol., 88(5):2633-2644, Mar 2014. PubMed ID: 24352444. Show all entries for this paper.

Wiehe2014 Kevin Wiehe, David Easterhoff, Kan Luo, Nathan I. Nicely, Todd Bradley, Frederick H. Jaeger, S. Moses Dennison, Ruijun Zhang, Krissey E. Lloyd, Christina Stolarchuk, Robert Parks, Laura L. Sutherland, Richard M. Scearce, Lynn Morris, Jaranit Kaewkungwal, Sorachai Nitayaphan, Punnee Pitisuttithum, Supachai Rerks-Ngarm, Faruk Sinangil, Sanjay Phogat, Nelson L. Michael, Jerome H. Kim, Garnett Kelsoe, David C. Montefiori, Georgia D. Tomaras, Mattia Bonsignori, Sampa Santra, Thomas B. Kepler, S. Munir Alam, M. Anthony Moody, Hua-Xin Liao, and Barton F. Haynes. Antibody Light-Chain-Restricted Recognition of the Site of Immune Pressure in the RV144 HIV-1 Vaccine Trial Is Phylogenetically Conserved. Immunity, 41(6):909-918, 18 Dec 2014. PubMed ID: 25526306. 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.

Astronomo2016 Rena D. Astronomo, Sampa Santra, Lamar Ballweber-Fleming, Katharine G. Westerberg, Linh Mach, Tiffany Hensley-McBain, Laura Sutherland, Benjamin Mildenberg, Georgeanna Morton, Nicole L. Yates, Gregory J. Mize, Justin Pollara, Florian Hladik, Christina Ochsenbauer, Thomas N. Denny, Ranjit Warrier, Supachai Rerks-Ngarm, Punnee Pitisuttithum, Sorachai Nitayapan, Jaranit Kaewkungwal, Guido Ferrari, George M. Shaw, Shi-Mao Xia, Hua-Xin Liao, David C. Montefiori, Georgia D. Tomaras, Barton F. Haynes, and Juliana M. McElrath. Neutralization Takes Precedence Over IgG or IgA Isotype-related Functions in Mucosal HIV-1 Antibody-mediated Protection. EBioMedicine, 14:97-111, Dec 2016. PubMed ID: 27919754. Show all entries for this paper.