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Notes

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• 4B3: 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. 4B3 and A32 were selected as nonneutralizing mAbs with high ADCC activity and targeting cluster I of gp41. Cheeseman2017 (genital and mucosal immunity, immunoprophylaxis)
• 4B3: A panel of NAbs and non-neutralizing Abs (NoNAbs) displaying the highest Fc γR-mediated inhibitory activity and significant ADCC were selected and formulated in a microbicidal gel and tested for their antiviral activity against SHIVSF162P3 vaginal challenge in non-human primates. Combination of 2G12, 2F5 and 4E10 fully prevented vaginal transmission. Two NoNAbs 246-D and 4B3 had no impact on viral acquisition, but reduced plasma viral load. Moog2014 (ADCC, SIV)
• 4B3: The complexity of the epitopes recognized by ADCC responses in HIV-1 infected individuals and candidate vaccine recipients is discussed in this review. 4B3 is discussed as the Cluster I region and Principal Immune Domain (PID) targeting non-neutralizing anti-gp41 mAb exhibiting ADCC activity and having a linear epitope. Pollara2013 (ADCC, review)
• 4B3: One of 24 MAbs and Fabs in this database that bind to the highly immunogenic gp41 cluster I region (aa 579 - 604). Only one of these has any neutralizing potential, clone 3. Gorny2003 (review)
• 4B3: Generated by electrofusion of PBL from HIV-1 positive volunteers with CB-F7 cells. Buchacher1992,Buchacher1994 (antibody generation)

References

Showing 7 of 7 references.

Isolation Paper
Buchacher1994 A. Buchacher, R. Predl, K. Strutzenberger, W. Steinfellner, A. Trkola, M. Purtscher, G. Gruber, C. Tauer, F. Steindl, A. Jungbauer, and H. Katinger. Generation of Human Monoclonal Antibodies against HIV-1 Proteins; Electrofusion and Epstein-Barr Virus Transformation for Peripheral Blood Lymphocyte Immortalization. AIDS Res. Hum. Retroviruses, 10:359-369, 1994. A panel of 33 human monoclonal antibodies were produced. Linear epitopes for some of this set of MAbs were mapped using peptide ELISA. Linear epitopes were mapped in gp41, and a single epitope was mapped in p24. While multiple gp120 specific MAbs were generated, all seemed to be conformational or carbohydrate dependent, or both. PubMed ID: 7520721. Show all entries for this paper.

Buchacher1992 Andrea Buchacher, Renate Predl, Christa Tauer, Martin Purtscher, Gerhard Gruber, Renate Heider, Fraz Steindl, Alexandra Trkola, Alois Jungbauer, and Herman Katinger. Human Monoclonal Antibodies against gp41 and gp120 as Potential Agent for Passive Immunization. Vaccines, 92:191-195, 1992. 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.

Chen1994 Y.-H. Chen, A. Susanna, G. Bock, F. Steindl, H. Katinger, and M. P. Dierich. HIV-1 gp41 Shares a Common Immunologic Determinant with Human T, B and Monocyte Cell Lines. Immunol. Lett., 39:219-222, 1994. The MAb 3D6 binds to HIV gp41, and to a 43 kd protein found in human T, B and monocyte cell lines. The authors suggest the possibility of molecular mimicry. PubMed ID: 7518416. Show all entries for this paper.

Gorny2003 Miroslaw K. Gorny and Susan Zolla-Pazner. Human Monoclonal Antibodies that Neutralize HIV-1. In Bette T. M. Korber and et. al., editors, HIV Immunology and HIV/SIV Vaccine Databases 2003. pages 37--51. Los Alamos National Laboratory, Theoretical Biology \& Biophysics, Los Alamos, N.M., 2004. URL: http://www.hiv.lanl.gov/content/immunology/pdf/2003/zolla-pazner_article.pdf. LA-UR 04-8162. Show all entries for this paper.

Moog2014 C. Moog, N. Dereuddre-Bosquet, J.-L. Teillaud, M. E. Biedma, V. Holl, G. Van Ham, L. Heyndrickx, A. Van Dorsselaer, D. Katinger, B. Vcelar, S. Zolla-Pazner, I. Mangeot, C. Kelly, R. J. Shattock, and R. Le Grand. Protective Effect of Vaginal Application of Neutralizing and Nonneutralizing Inhibitory Antibodies Against Vaginal SHIV Challenge in Macaques. Mucosal Immunol., 7(1):46-56, Jan 2014. PubMed ID: 23591718. 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.