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MAb ID	8.22.2 (Xeno-mAb 8.22.2)
HXB2 Location	gp160(162-178) DNA(6708..6758)	gp160 Epitope Map
Author Location	gp120(gp120 )
Research Contact	Dr. Abraham Pinter, Public Health Research Institute, Newark, NJ, pinter@phri.org
Epitope	TTSIRDKVQKEYALFYK	Epitope Alignment
Ab Type	gp120 V2 // V2 glycan(V2g) // V2 apex
Neutralizing
Species (Isotype)	transgenic mouse(IgG2κ)
Patient
Immunogen	vaccine
Keywords	antibody binding site, antibody generation, neutralization, review, subtype comparisons, vaccine antigen design, vaccine-induced immune responses, variant cross-reactivity

Vaccine Details

Notes

Showing 8 of 8 notes.

• 8.22.2: The study evaluated the influence of glycosylation within the V1/V2 domain on antibody recognition. Recombinant proteins, demonstrated to be folded in native conformation, were produced following transfection of CHO cells by plasmids expressing V1/V2 domains from primary isolates of different clades. This Ab was used to validate the functional structure of the recombinant proteins produced. Granados-Gonzalez2008
• 8.22.2: This Ab was used to help define the antigenic profile of envelopes used in serum depletion experiments to attempt to define the neutralizing specificities of broadly cross-reactive neutralizing serum. This Ab bound to JR-FL and JR-CSF gp120 monomers but not to core JR-CSF gp120 monomer used in the same experiments. V1, V2, and V3 specificities did not contribute to the broadly neutralizing capability of sera from 3 (2 B clade ,1 A clade) HIV infected individuals. Dhillon2007 (antibody binding site, neutralization)
• 8.22.2: Antigens were designed to attempt to target immune responses toward the IgG1b12 epitope, while minimizing antibody responses to less desirable epitopes. One construct had a series of substitutions near the CD4 binding site (GDMR), the other had 7 additional glycans (mCHO). The 2 constructs did not elicit b12-like neutralizing antibodies, but both antigens successfully dampened other responses that were intended to be dampened while not obscuring b12 binding. V2 MAb 697-D did not bind to mCHO and had diminished binding to GDMR, while V2 MAb 8.22.2 bound to GDMR but not mCHO. Selvarajah2005 (vaccine antigen design, vaccine-induced immune responses)
• 8.22.2: By adding N-linked glycosylation sites to gp120, epitope masking of non-neutralizing epitopes can be achieved leaving the IgG1b12 binding site intact. This concept was originally tested with the addition of four glycosylation sites, but binding to b12 was reduced. It was modified here to exclude the C1 N-terminal region, and to include only three additional glycosylation sites. This modified protein retains full b12 binding affinity and it masks other potentially competing epitopes, and does not bind to 21 other MAbs to 7 epitopes on gp120, including 8.22.2. Pantophlet2004 (vaccine antigen design)
• 8.22.2: V1V2 was determined to be the region that conferred the neutralization phenotype differences between two R5-tropic primary HIV-1 isolates, JRFL and SF162. JRFL is resistant to neutralization by many sera and MAbs, while SF162 is sensitive. All MAbs tested, anti-V3, -V2, -CD4BS, and -CD4i, (except the broadly neutralizing MAbs IgG1b12, 2F5, and 2G12, which neutralized both strains), neutralized the SF162 pseudotype but not JRFL, and chimeras that exchanged the V1V2 loops transferred the neutralization phenotype. Three anti-V2 MAb were tested -- 8.22.2 weakly neutralized SF162, and did not neutralize JRFL at all. Pinter2004 (variant cross-reactivity)
• 8.22.2: This broad review of anti-Envelope MAbs notes that V2 MAbs are generally weakly neutralizing at best, and somewhat strain specific. 8.22.2 weakly neutralizes SF162. Gorny2003 (review)
• 8.22.2: This epitope is similar to a fragment of the human protein macrophage colony stimulating factor I receptor SISIRLKVQK. Maksiutov2002
• 8.22.2 : Transgenic mice (strain XenoMouse G2) carrying human genes allowing production of fully human IgG2kappa MAbs were used to rapidly create a panel of anti-HIV gp120 MAb-producing hybridomas by immunization with HIV SF162 gp120 -- several of the MAbs obtained were effective at neutralizing the autologous strain -- 8.22.2 was the only V2-specific MAb created and it could cross-compete with MAb 697D -- 8.22.2 could cross-react with BaL and JR-FL, two B clade R5 strains, but not B clade X4 or E clade viruses, and it could weakly neutralize autologous strain SF162. He2002 (antibody binding site, antibody generation, variant cross-reactivity, subtype comparisons)

References

Showing 8 of 8 references.

Isolation Paper
He2002 Yuxian He, William J. Honnen, Chavdar P. Krachmarov, Michael Burkhart, Samuel C. Kayman, Jose Corvalan, and Abraham Pinter. Efficient Isolation of Novel Human Monoclonal Antibodies with Neutralizing Activity Against HIV-1 from Transgenic Mice Expressing Human Ig Loci. J. Immunol., 169(1):595-605, 1 Jul 2002. PubMed ID: 12077293. Show all entries for this paper.

Dhillon2007 Amandeep K. Dhillon, Helen Donners, Ralph Pantophlet, Welkin E. Johnson, Julie M. Decker, George M. Shaw, Fang-Hua Lee, Douglas D. Richman, Robert W. Doms, Guido Vanham, and Dennis R. Burton. Dissecting the Neutralizing Antibody Specificities of Broadly Neutralizing Sera from Human Immunodeficiency Virus Type 1-Infected Donors. J. Virol., 81(12):6548-6562, Jun 2007. PubMed ID: 17409160. 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.

Granados-Gonzalez2008 Viviana Granados-Gonzalez, Julien Claret, Willy Berlier, Nadine Vincent, Silvio Urcuqui-Inchima, Frederic Lucht, Christiane Defontaine, Abraham Pinter, Christian Genin, and Serge Riffard. Opposite Immune Reactivity of Serum IgG and Secretory IgA to Conformational Recombinant Proteins Mimicking V1/V2 Domains of Three Different HIV Type 1 Subtypes Depending on Glycosylation. AIDS Res. Hum. Retroviruses, 24(2):289-299, Feb 2008. PubMed ID: 18260782. Show all entries for this paper.

Maksiutov2002 A. Z. Maksiutov, A. G. Bachinskii, and S. I. Bazhan. [Searching for Local Similarities Between HIV-1 and Human Proteins. Application to Vaccines]. Mol Biol (Mosk), 36(3):447-459, May-Jun 2002. Article in Russian. PubMed ID: 12068630. Show all entries for this paper.

Pantophlet2004 R. Pantophlet, I. A. Wilson, and D. R. Burton. Improved Design of an Antigen with Enhanced Specificity for the Broadly HIV-Neutralizing Antibody b12. Protein Eng. Des. Sel., 17(10):749-758, Oct 2004. PubMed ID: 15542540. Show all entries for this paper.

Pinter2004 Abraham Pinter, William J. Honnen, Yuxian He, Miroslaw K. Gorny, Susan Zolla-Pazner, and Samuel C. Kayman. The V1/V2 Domain of gp120 Is a Global Regulator of the Sensitivity of Primary Human Immunodeficiency Virus Type 1 Isolates to Neutralization by Antibodies Commonly Induced upon Infection. J. Virol., 78(10):5205-5215, May 2004. PubMed ID: 15113902. Show all entries for this paper.

Selvarajah2005 Suganya Selvarajah, Bridget Puffer, Ralph Pantophlet, Mansun Law, Robert W. Doms, and Dennis R. Burton. Comparing Antigenicity and Immunogenicity of Engineered gp120. J. Virol., 79(19):12148-12163, Oct 2005. PubMed ID: 16160142. Show all entries for this paper.