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Epitope Mapping of Conformational V2-specific Anti-HIV Human Monoclonal Antibodies Reveals an Immunodominant Site in V2
Mayr, Luzia M; Cohen, Sandra; Spurrier, Brett; Kong, Xiang-Peng; Zolla-Pazner, Susan
In the case-control study of the RV144 vaccine trial, the levels of antibodies to the V1V2 region of the gp120 envelope glycoprotein were found to correlate inversely with risk of HIV infection. This recent demonstration of the potential role of V1V2 as a vaccine target has catapulted this region into the focus of HIV-1 research. We previously described seven human monoclonal antibodies (mAbs) derived from HIV-infected individuals that are directed against conformational epitopes in the V1V2 domain. In this study, using lysates of SF162 pseudoviruses carrying V1V2 mutations, we mapped the epitopes of these seven mAbs. All tested mAbs demonstrated a similar binding pattern in which three mutations (F176A, Y177T, and D180L) abrogated binding of at least six of the seven mAbs to =15% of SF162 wildtype binding. Binding of six or all of the mAbs was reduced to =50% of wildtype by single substitutions at seven positions (168, 180, 181, 183, 184, 191, and 193), while one change, V181I, increased the binding of all mAbs. When mapped onto a model of V2, our results suggest that the epitope of the conformational V2 mAbs is located mostly in the disordered region of the available crystal structure of V1V2, overlapping and surrounding the alpha4beta7 binding site on V2.
PMCID:3726596
PMID: 23923028
ISSN: 1932-6203
CID: 484202
Skin tattooing as a novel approach for DNA vaccine delivery
Chiu, Yung-Nung; Sampson, Jared M; Jiang, Xunqing; Zolla-Pazner, Susan B; Kong, Xiang-Peng
Nucleic acid-based vaccination is a topic of growing interest, especially plasmid DNA (pDNA) encoding immunologically important antigens. After the engineered pDNA is administered to the vaccines, it is transcribed and translated into immunogen proteins that can elicit responses from the immune system. Many ways of delivering DNA vaccines have been investigated; however each delivery route has its own advantages and pitfalls. Skin tattooing is a novel technique that is safe, cost-effective, and convenient. In addition, the punctures inflicted by the needle could also serve as a potent adjuvant. Here, we a) demonstrate the intradermal delivery of plasmid DNA encoding enhanced green fluorescent protein (pCX-EGFP) in a mouse model using a tattooing device and b) confirm the effective expression of EGFP in the skin cells using confocal microscopy.
PMCID:3490318
PMID: 23117298
ISSN: 1940-087x
CID: 202152
Biophysical dissection of the antigen-antibody interaction of the broadly reactive anti-V3 human mAb 447-52D [Meeting Abstract]
Killikelly, A.; Zhang, H.; Spurrier, B.; Williams, C.; Gorny, M. K.; Zolla-Pazner, S.; Kong, X.
ISI:000309472100140
ISSN: 1742-4690
CID: 181482
Crystal structure analysis of anti-V2 mAb 2158 suggests a conformational epitope involving an N-linked glycan [Meeting Abstract]
Spurrier, B.; Pan, R.; Sampson, J.; Williams, C.; Gorny, M.; Zolla-Pazner, S.; Kong, X.
ISI:000309472100143
ISSN: 1742-4690
CID: 181512
High-resolution crystal structure of the Fv of quaternary neutralizing epitope mAb 2909 reveals atomic details of its antigen-binding site [Meeting Abstract]
Sampson, J. M.; Killikelly, A.; Zhang, H.; Gorny, M. K.; Zolla-Pazner, S.; Kong, X.
ISI:000309472100152
ISSN: 1742-4690
CID: 181532
The efficiency of bridging sheet recruitment determines HIV-1 R5 envelope sensitivity to soluble CD4 and macrophage tropism [Meeting Abstract]
O'Connell, O.; Repik, A.; Reeves, J. D.; Gonzalez-Perez, M. P.; Quitadamo, B.; Duenas-Decamp, M.; Peters, P.; Lin, R.; Anton, E. D.; Zolla-Pazner, S.; Corti, D.; Wallace, A.; Wang, S.; Kong, X.; Lu, S.; Clapham, P. R.
ISI:000309472100214
ISSN: 1742-4690
CID: 181542
Skin tattooing as an effective tool for delivering DNA and protein vaccine immunogens [Meeting Abstract]
Chiu, Y.; Jiang, X.; Kumar, R.; Hioe, C. E.; Zolla-Pazner, S.; Kong, X.
ISI:000309472100411
ISSN: 1742-4690
CID: 181562
A novel rabbit monoclonal antibody platform to dissect the diverse repertoire of antibody epitopes for HIV-1 Env immunogen design [Meeting Abstract]
Chen, Y.; Vaine, M.; Kong, X.; Montefiori, D.; Wang, S.; Lu, S.
ISI:000309472100156
ISSN: 1742-4690
CID: 181592
Sequential exposure to specific antibody escape mutations may program neutralization breadth during subtype A HIV-1 infection [Meeting Abstract]
Murphy, M. K.; Yue, L.; Pan, R.; Boliar, S.; Sethi, A.; Karita, E.; Allen, S. A.; Cormier, E.; Robinson, J. E.; Gnanakaran, S.; Hunter, E.; Kong, X.; Derdeyn, C. A.
ISI:000309472100177
ISSN: 1742-4690
CID: 181612
Structural analyses of antigen binding similarities and differences between rabbit and human anti-gp120 V3 mAbs [Meeting Abstract]
Pan, R.; Sampson, J. M.; Chen, Y.; Vaine, M.; Wang, S.; Lu, S.; Kong, X.
ISI:000309472100149
ISSN: 1742-4690
CID: 181652