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 may be able to 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 line of research in the Pinter lab is exploiting the human humoral response to identify novel antibodies and epitopes that may have clinical utility. In addition to the focus on HIV, these studies have recently been extended towards mycobacterial pathogens, including M.tb, the infectious agent for tuberculosis. This has led to the isolation and characterization of novel monoclonal antibodies (mAbs) from infected patients with high affinities towards the major surface glycolipid of M.tb, lipoarabinomannan (LAM). These antibodies have allowed the development of a sensitive assay that can detect the presence of LAM in the urine of most patients actively infected with TB. Current studies are directed at improving the sensitivity of these reagents so that they can be developed as an effective point-of-care assay for TB infection, and to study the potential of human mAbs against LAM and other protein and glycoprotein TB antigens to control M.tb. infection and pathogenicity.
Yates NL, deCamp AC, Korber BT, Liao HX, Irene C, Pinter A, Peacock J, Harris LJ, Sawant S, Hraber P, Shen X, Rerks-Ngarm S, Pitisuttithum P, Nitayapan S, Berman PW, Robb ML, Pantaleo G, Zolla-Pazner S, Haynes BF, Alam SM, Montefiori DC, Tomaras GD (2018) HIV-1 Envelope Glycoproteins from Diverse Clades Differentiate Antibody Responses and Durability among Vaccinees. J Virol. PMI: 29386288
Sigal GB, Pinter A, Lowary TL, Kawasaki M, Li A, Mathew A, Tsionsky M, Zheng RB, Plisova T, Shen K, Katsuragi K, Choudhary A, Honnen WJ, Nahid P, Denkinger CM, Broger T (2018) A novel sensitive immunoassay targeting the MTX-Lipoarabinomannan epitope meets the WHO’s performance target for Tuberculosis diagnosis. J Clin Microbiol. PMI: 30257899
Qualls ZM, Choudhary A, Honnen W, Prattipati R, Robinson JE, Pinter A (2018) Identification of Novel Structural Determinants in MW965 Env That Regulate the Neutralization Phenotype and Conformational Masking Potential of Primary HIV-1 Isolates. J Virol 92. PMI: 29237828
Choudhary A, Patel D, Honnen W, Lai Z, Prattipati R, Hsueh Y-C, Gennaro ML, Lardizabal A, Joe M, Bai Y, Spencer J, Lowary TL, Pinter A (2018) Novel human monoclonal antibodies with distinct epitope specificities help characterize the antigenic diversity of lipoarabinomannan (LAM), the major surface glycolipid of Mycobacterium tuberculosis. Journal of Immunology In press.: PMI:
Amin AG, De P, Spencer JS, Brennan PJ, Daum J, Andre BG, Joe M, Bai Y, Laurentius L, Porter MD, Honnen WJ, Choudhary A, Lowary TL, Pinter A, Chatterjee D (2018) Detection of lipoarabinomannan in urine and serum of HIV-positive and HIV-negative TB suspects using an improved capture-enzyme linked immuno absorbent assay and gas chromatography/mass spectrometry. Tuberculosis (Edinb) 111: 178-187. PMI: 30029905
Perez LG, Martinez DR, deCamp AC, Pinter A, Berman PW, Francis D, Sinangil F, Lee C, Greene K, Gao H, Nitayaphan S, Rerks-Ngarm S, Kaewkungwal J, Pitisuttithum P, Tartaglia J, O’Connell RJ, Robb ML, Michael NL, Kim JH, Gilbert P, Montefiori DC (2017) V1V2-specific complement activating serum IgG as a correlate of reduced HIV-1 infection risk in RV144. PLoS One 12: e0180720. PMI: 28678869
Nabi R, Moldoveanu Z, Wei Q, Golub ET, Durkin HG, Greenblatt RM, Herold BC, Nowicki MJ, Kassaye S, Cho MW, Pinter A, Landay AL, Mestecky J, Kozlowski PA (2017) Differences in serum IgA responses to HIV-1 gp41 in elite controllers compared to viral suppressors on highly active antiretroviral therapy. PLoS One 12: e0180245. PMI: 28671952
Bradley T, Pollara J, Santra S, Vandergrift N, Pittala S, Bailey-Kellogg C, Shen X, Parks R, Goodman D, Eaton A, Balachandran H, Mach LV, Saunders KO, Weiner JA, Scearce R, Sutherland LL, Phogat S, Tartaglia J, Reed SG, Hu SL, Theis JF, Pinter A, Montefiori DC, Kepler TB, Peachman KK, Rao M, Michael NL, Suscovich TJ, Alter G, Ackerman ME, Moody MA, Liao HX, Tomaras G, Ferrari G, Korber BT, Haynes BF (2017) Pentavalent HIV-1 vaccine protects against simian-human immunodeficiency virus challenge. Nat Commun 8: 15711. PMI: 28593989
Tian J, Lopez CA, Derdeyn CA, Jones MS, Pinter A, Korber B, Gnanakaran S (2016) Effect of Glycosylation on an Immunodominant Region in the V1V2 Variable Domain of the HIV-1 Envelope gp120 Protein. PLoS Comput Biol 12: e1005094. PMI: 27716795
Yates NL, Liao HX, Fong Y, deCamp A, Vandergrift NA, Williams WT, Alam SM, Ferrari G, Yang ZY, Seaton KE, Berman PW, Alpert MD, Evans DT, O’Connell RJ, Francis D, Sinangil F, Lee C, Nitayaphan S, Rerks-Ngarm S, Kaewkungwal J, Pitisuttithum P, Tartaglia J, Pinter A, Zolla-Pazner S, Gilbert PB, Nabel GJ, Michael NL, Kim JH, Montefiori DC, Haynes BF, Tomaras GD (2014) Vaccine-induced Env V1-V2 IgG3 correlates with lower HIV-1 infection risk and declines soon after vaccination. Sci Transl Med 6: 228ra239. PMI: 24648342