Public Health Research Institute Center
UMDNJ - New Jersey Medical School
225 Warren Street
Newark, New Jersey 07103

Phone: (973) 854-3300
e-mail: pinterab@umdnj.edu


Research Summary

With the inability of available HIV-1 vaccines to achieve protection, there is a clear need for the identification of novel vaccine targets and approaches. A key focus of the work of Dr. Pinter's lab is understanding the basis for the inability of the immune system to control HIV, and identification of new targets and vaccine approaches that can overcome these limitations. The role of conformational masking towards neutralization resistance is being analyzed in detail, with a focus on specific determinants that contribute to masking and identification of mutations that can reverse this effect.

A second approach is based on the identification of antibodies in sera of HIV-infected subjects that possess broad and potent neutralizing activities. The nature of the targets of these antibodies is not known, but it is clear these do not represent standard well-characterized epitopes. In a number of cases, there is evidence that these may involve quaternary targets that are dependent on the native trimeric Env structure. Immune sera are being screened for such activities, and the antibodies and epitopes that are involved are being characterized. Monoclonal antibodies possessing similar activities are being cloned from B cells of infected humans and immunized macaques, and the activities and specificities of these antibodies are being defined. The information derived from these studies is being used to design immunogens and vaccination strategies for inducing such broadly protective antibody responses.





Selected Publications

Moore PL, Gray ES, Sheward D, Madiga M, Ranchobe N, Lai Z, Honnen WJ, Nonyane M, Tumba N, Hermanus T, Sibeko S, Mlisana K, Abdool Karim SS, Williamson C, Pinter A, Morris L (2011) Potent and broad neutralization of HIV-1 subtype C by plasma antibodies targeting a quaternary epitope including residues in the V2 loop. J Virol 85: 3128-3141. PMI: 21270156

Krachmarov C, Lai Z, Honnen WJ, Salomon A, Gorny MK, Zolla-Pazner S, Robinson J, Pinter A (2011) Characterization of structural features and diversity of variable region determinants of related quaternary epitopes recognized by human and rhesus macaque MAbs possessing unusually potent neutralizing activities. Journal of virology 85: 10730-10740. PMI: 21835798

Totrov M, Jiang X, Kong XP, Cohen S, Krachmarov C, Salomon A, Williams C, Seaman MS, Abagyan R, Cardozo T, Gorny MK, Wang S, Lu S, Pinter A, Zolla-Pazner S (2010) Structure-guided design and immunological characterization of immunogens presenting the HIV-1 gp120 V3 loop on a CTB scaffold. Virology 405: 513-523. PMI: 20663531

Lynch RM, Rong R, Li B, Shen T, Honnen W, Mulenga J, Allen S, Pinter A, Gnanakaran S, Derdeyn CA (2010) Subtype-specific conservation of isoleucine 309 in the envelope V3 domain is linked to immune evasion in subtype C HIV-1 infection. Virology 404: 59-70. PMI: 20494390

Zolla-Pazner S, Cohen S, Pinter A, Krachmarov C, Wrin T, Wang S, Lu S (2009) Cross-clade neutralizing antibodies against HIV-1 induced in rabbits by focusing the immune response on a neutralizing epitope. Virology 392: 82-93. PMI: 19632700

Rong R, Li B, Lynch RM, Haaland RE, Murphy MK, Mulenga J, Allen SA, Pinter A, Shaw GM, Hunter E, Robinson JE, Gnanakaran S, Derdeyn CA (2009) Escape from autologous neutralizing antibodies in acute/early subtype C HIV-1 infection requires multiple pathways. PLoS Pathog 5: e1000594. PMI: 19763269

Granados-Gonzalez V, Piedrahita LD, Martinez-Gutierrez M, Lawrence P, Saoudin H, Zapata X, Lucht F, Pinter A, Genin C, Urcuqui-Inchima S, Riffard S (2009) Neutralizing inter-clade cross-reactivity of HIV-1 V1/V2-specific secretory immunoglobulin A in Colombian and French cohorts. AIDS 23: 2219-2222. PMI: 19830891

Gorny MK, Wang XH, Williams C, Volsky B, Revesz K, Witover B, Burda S, Urbanski M, Nyambi P, Krachmarov C, Pinter A, Zolla-Pazner S, Nadas A (2009) Preferential use of the VH5-51 gene segment by the human immune response to code for antibodies against the V3 domain of HIV-1. Mol Immunol 46: 917-926. PMI: 18952295

Davis KL, Gray ES, Moore PL, Decker JM, Salomon A, Montefiori DC, Graham BS, Keefer MC, Pinter A, Morris L, Hahn BH, Shaw GM (2009) High titer HIV-1 V3-specific antibodies with broad reactivity but low neutralizing potency in acute infection and following vaccination. Virology 387: 414-426. PMI: 19298995

Davis KL, Bibollet-Ruche F, Li H, Decker JM, Kutsch O, Morris L, Salomon A, Pinter A, Hoxie JA, Hahn BH, Kwong PD, Shaw GM (2009) Human immunodeficiency virus type 2 (HIV-2)/HIV-1 envelope chimeras detect high titers of broadly reactive HIV-1 V3-specific antibodies in human plasma. J Virol 83: 1240-1259. PMI: 19019969

Zolla-Pazner S, Cohen SS, Krachmarov C, Wang S, Pinter A, Lu S (2008) Focusing the immune response on the V3 loop, a neutralizing epitope of the HIV-1 gp120 envelope. Virology 372: 233-246. PMI: 18061228

Pinter A (2007) Roles of HIV-1 Env variable regions in viral neutralization and vaccine development. Curr HIV Res 5: 542-553. PMI: 18045110

Honnen WJ, Krachmarov C, Kayman SC, Gorny MK, Zolla-Pazner S, Pinter A (2007) Type-specific epitopes targeted by monoclonal antibodies with exceptionally potent neutralizing activities for selected strains of human immunodeficiency virus type 1 map to a common region of the V2 domain of gp120 and differ only at single positions from the clade B consensus sequence. J Virol 81: 1424-1432. PMI: 17121806

Krachmarov CP, Honnen WJ, Kayman SC, Gorny MK, Zolla-Pazner S, Pinter A (2006) Factors determining the breadth and potency of neutralization by V3-specific human monoclonal antibodies derived from subjects infected with clade A or clade B strains of human immunodeficiency virus type 1. J Virol 80: 7127-7135. PMI: 16809318

Gorny MK, Williams C, Volsky B, Revesz K, Wang XH, Burda S, Kimura T, Konings FA, Nadas A, Anyangwe CA, Nyambi P, Krachmarov C, Pinter A, Zolla-Pazner S (2006) Cross-clade neutralizing activity of human anti-V3 monoclonal antibodies derived from the cells of individuals infected with non-B clades of human immunodeficiency virus type 1. J Virol 80: 6865-6872. PMI: 16809292

Pinter A, Honnen WJ, D'Agostino P, Gorny MK, Zolla-Pazner S, Kayman SC (2005) The C108g epitope in the V2 domain of gp120 functions as a potent neutralization target when introduced into envelope proteins derived from human immunodeficiency virus type 1 primary isolates. J Virol 79: 6909-6917. PMI: 15890930

Krachmarov C, Pinter A, Honnen WJ, Gorny MK, Nyambi PN, Zolla-Pazner S, Kayman SC (2005) Antibodies that are cross-reactive for human immunodeficiency virus type 1 clade a and clade B v3 domains are common in patient sera from Cameroon, but their neutralization activity is usually restricted by epitope masking. J Virol 79: 780-790. PMI: 15613306

Burkhart MD, D'Agostino P, Kayman SC, Pinter A (2005) Involvement of the C-terminal disulfide-bonded loop of murine leukemia virus SU protein in a postbinding step critical for viral entry. J Virol 79: 7868-7876. PMI: 15919941

Pinter A, Honnen WJ, He Y, Gorny MK, Zolla-Pazner S, Kayman SC (2004) 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: 5205-5215. PMI: 15113902




C.V.

Education
Brooklyn College, Brooklyn, New York, B.S., 1969 (Chemistry); Columbia University, New York, N.Y., Ph.D., 1973 (Chemistry); Rockefeller University, New York, N.Y., Post Doc., 1974-1975 (Animal Virology); Memorial Sloan-Kettering Cancer Center, New York, N.Y., Post Doc., 1976-1976 (Viral Oncology).

Academic Positions
Memorial Sloan-Kettering Cancer Center, Research Associate, Laboratory of Viral Oncology, 1976-1978; York College of the CUNY, Adjunct Assistant Professor, Department of Chemistry, 1978-1982; Memorial Sloan-Kettering Cancer Center, Associate, Laboratory of Viral Oncology, 1979-1982; Cornell University Graduate School of Medical Sciences, Assistant Professor, Department of Genetics and Molecular Biology, Sloan-Kettering Division, 1980-1985; Memorial Sloan-Kettering Cancer Center, Assistant Member, Laboratory of Viral Oncology, 1982-1985; NYU School of Medicine, Research Associate Professor, Department of Microbiology, 1985-1990; Public Health Research Institute, Associate Member, Head, Laboratory of Retroviral Biology, 1985-1990; NYU School of Medicine, Research Professor, Department of Microbiology, 1991-present; Public Health Research Institute, Member, Head, Laboratory of Retroviral Biology, 1991-present; UMNDJ, Professor, Department of Microbiology & Medical Genetics, 2002-present.

Awards & Professional Societies and Committees
Phi Beta Kappa, 1969; Sigma Xi, 1972; NIH Postdoctoral Fellow, 1974-76; Member, American Society of Microbiology, 1974-present; Charter Member, American Society of Virology, 1982; Special Fellow, Leukemia Society of America, 1979-1981; Member, International Association for Comparative Research on Leukemia and Related Diseases, 1985-present; Member, International AIDS Society, 1989-present; Ad Hoc Member, Experimental Virology Study Section, NIH, 06/1986; Member, Special Review Committee, NCVDG for the Treatment of AIDS, NIAID, 05/1987; Member, NIAID AIDS Review Committee, 1987-1991, NIH Reviewers Reserve, 1991-1995; Member, Editorial Board, Journal of Virology, 1992-2001.