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Displaying record number 2894

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MAb ID	CH22
HXB2 Location	gp160(304-320) DNA(7134..7184)	gp160 Epitope Map
Author Location	gp120
Epitope	RKRIHIGPGRAFYTT	Epitope Alignment
Subtype	B, CRF01_AE
Ab Type	gp120 V3 // V3 glycan (V3g)
Neutralizing	yes
Species (Isotype)	human(IgG1)
Patient
Immunogen	vaccine
Country	Thailand
Keywords	ADCC, antibody binding site, antibody generation, antibody polyreactivity, genital and mucosal immunity, immunoprophylaxis, review, SIV, structure, vaccine-induced immune responses

Notes

Showing 5 of 5 notes.

• CH22: The ability of neutralizing and nonneutralizing mAbs to block infection in models of mucosal transmission was tested. Neutralization potency did not fully predict activity in mucosal tissue. CD4bs-specific bNAbs, in particular VRC01, blocked HIV-1 infection across all cellular and tissue models. MPER (2F5) and outer domain glycan (2G12) bNAbs were also efficient in preventing infection of mucosal tissues, while bNAbs targeting V1-V2 glycans (PG9 and PG16) were more variable. Non-nAbs alone and in combinations, were poorly protective against mucosal infection. The protection provided by specific bNAbs demonstrates their potential over that of nonneutralizing antibodies for preventing mucosal entry. Three non-nAb combinations were assayed: 7B2/CH58/CH90, 7B2/CH58/CH22, and F240/M785-U1/N10-U1; ; A32, 7B2, CH90, and CH22 contained the AAA mutations (S298A, E333A, and K334A) optimized for binding to Fc RIIIa (CD16) and to augment antibody ADCC activity. Cheeseman2017 (genital and mucosal immunity, immunoprophylaxis)
• CH22: In a passive antibody infusion-rhesus macaque challenge model, non-neutralizing mAbs were seen to limit virus acquisition and infection. 7B2, which recognizes both virus particles and infected cells as well as A32, recognizing only infected cells, together were able to decrease transmitted/founder viruses in in vivo rectal mucosal high-dose transmission of SHIV-BaL by 50% though they did not prevent infection or reduce viral load. CH22, a V3-loop bNAb was able to eliminate all transmission of SHIV by intra-rectal route in 4/6 subjects. Santra2015 (genital and mucosal immunity, SIV, structure)
• CH22: A panel of Env-specific mAbs was isolated from 6 HIV1-infected lactating women. Antibodies in colostrum may help prevent mucosal infection of the infant, so this study aimed to define milk IgGs for future vaccination strategies to reduce HIV transmission during lactation. Despite the high rate of VH 1-69 usage among colostrum Env specific B cells, it did not correlate with distinct gp120 epitope specificity or function. CH22 was compared to the newly-derived mAbs; it had no cross-reactivity with gut bacteria, and tested negative in onje test of autoreactivity. Jeffries2016 (antibody polyreactivity)
• CH22: The complexity of the epitopes recognized by ADCC responses in HIV-1 infected individuals and candidate vaccine recipients is discussed in this review. CH22, generated by a vaccine recipient of phase II RV135 clinical trial, is discussed as the V3 region-targeting, neutralizing anti-gp120 mAb exhibiting ADCC activity and having a linear epitope. Pollara2013 (ADCC, review)
• CH22: NAb response was compared in 2 HIV-1 vaccine efficacy trials in which either partial protection (RV144) or no protection (Vax003) was seen. The peak NAb response in RV144 was substantially weaker than the peak response in Vax003, suggesting that either weak neutralizing antibody responses can be partially protective in low-risk heterosexual populations or that the modest efficacy seen in RV144 was mediated by other immune responses. MAb CH22 was vaccine-induced antibody, isolated from subject T141485 in RV144 trial. CH22 used V-gene segment, had no detectable neutralizing activity against tier 2 viruses, but neutralized subtype B tier 1 viruses, and mapped to V3 linear peptide KRIHIGPGRAFYTT. Montefiori2012 (antibody binding site, antibody generation, vaccine-induced immune responses)

References

Showing 5 of 5 references.

Isolation Paper
Montefiori2012 David C. Montefiori, Chitraporn Karnasuta, Ying Huang, Hasan Ahmed, Peter Gilbert, Mark S. de Souza, Robert McLinden, Sodsai Tovanabutra, Agnes Laurence-Chenine, Eric Sanders-Buell, M. Anthony Moody, Mattia Bonsignori, Christina Ochsenbauer, John Kappes, Haili Tang, Kelli Greene, Hongmei Gao, Celia C. LaBranche, Charla Andrews, Victoria R. Polonis, Supachai Rerks-Ngarm, Punnee Pitisuttithum, Sorachai Nitayaphan, Jaranit Kaewkungwal, Steve G. Self, Phillip W. Berman, Donald Francis, Faruk Sinangil, Carter Lee, Jim Tartaglia, Merlin L. Robb, Barton F. Haynes, Nelson L. Michael, and Jerome H. Kim. Magnitude and Breadth of the Neutralizing Antibody Response in the RV144 and Vax003 HIV-1 Vaccine Efficacy Trials. J. Infect. Dis., 206(3):431-441, 1 Aug 2012. PubMed ID: 22634875. Show all entries for this paper.

Cheeseman2017 Hannah M. Cheeseman, Natalia J. Olejniczak, Paul M. Rogers, Abbey B. Evans, Deborah F. L. King, Paul Ziprin, Hua-Xin Liao, Barton F. Haynes, and Robin J. Shattock. Broadly Neutralizing Antibodies Display Potential for Prevention of HIV-1 Infection of Mucosal Tissue Superior to That of Nonneutralizing Antibodies. J. Virol., 91(1), 1 Jan 2017. PubMed ID: 27795431. Show all entries for this paper.

Jeffries2016 T. L. Jeffries, Jr., C. R. Sacha, J. Pollara, J. Himes, F. H. Jaeger, S. M. Dennison, E. McGuire, E. Kunz, J. A. Eudailey, A. M. Trama, C. LaBranche, G. G. Fouda, K. Wiehe, D. C. Montefiori, B. F. Haynes, H.-X. Liao, G. Ferrari, S. M. Alam, M. A. Moody, and S. R. Permar. The Function and Affinity Maturation of HIV-1 gp120-Specific Monoclonal Antibodies Derived from Colostral B Cells. Mucosal. Immunol., 9(2):414-427, Mar 2016. PubMed ID: 26242599. 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.

Santra2015 Sampa Santra, Georgia D Tomaras, Ranjit Warrier, Nathan I. Nicely, Hua-Xin Liao, Justin Pollara, Pinghuang Liu, S. Munir Alam, Ruijun Zhang, Sarah L. Cocklin, Xiaoying Shen, Ryan Duffy, Shi-Mao Xia, Robert J. Schutte, Charles W. Pemble, IV, S. Moses Dennison, Hui Li, Andrew Chao, Kora Vidnovic, Abbey Evans, Katja Klein, Amit Kumar, James Robinson, Gary Landucci, Donald N. Forthal, David C. Montefiori, Jaranit Kaewkungwal, Sorachai Nitayaphan, Punnee Pitisuttithum, Supachai Rerks-Ngarm, Merlin L. Robb, Nelson L. Michael, Jerome H. Kim, Kelly A. Soderberg, Elena E. Giorgi, Lily Blair, Bette T. Korber, Christiane Moog, Robin J. Shattock, Norman L. Letvin, Joern E. Schmitz, M. A. Moody, Feng Gao, Guido Ferrari, George M. Shaw, and Barton F. Haynes. Human Non-Neutralizing HIV-1 Envelope Monoclonal Antibodies Limit the Number of Founder Viruses during SHIV Mucosal Infection in Rhesus Macaques. PLoS Pathog., 11(8):e1005042, Aug 2015. PubMed ID: 26237403. Show all entries for this paper.