Donald N. Forthal
Professor of Medicine
Chief, Division of Infectious Diseases
Faculty, Center for Virus Research
Faculty, Institute for Immunology
Faculty, Pacific Southwest Center of Excellence for Biodefense and Emerging Infectious Diseases
Attending Physician, Infectious Disease Service
|Infectious Diseases; Viral Immunology; HIV, Antibody, Fc receptors, Antibody-Dependent Cellular Cytotoxicity|
|Dr. Forthal studies the immune response to viral infections. In particular, his research is focused on exploring how antibodies interact with cells of the immune system to prevent or modulate HIV infection. The research involves the use of in vitro and in vivo models of HIV infection with the eventual goal of developing vaccines and immunotherapies.|
Forthal DN, Gilbert PB, Landucci G, Phan T. Recombinant gp120 vaccine-induced antibodies inhibit clinical strains of HIV-1 in the presence of Fc receptor-bearing effector cells and correlate inversely with HIV infection rate. J Immunol 2007;178:6596-603.
Miller CJ, Genesca M, Abel K, Montefiori D, Forthal D, Bost K, Li J, Favre D, McCune JM. Antiviral antibodies are necessary for control of SIV replication. J Virol 2007;81 5024-35.
Hessell AJ, Hangartner L, Hunter M, Havenith CEG, Beurskens FJ, Bakker JM, Lanigan C, Landucci G, Forthal DN, Parren PWHI, Marx PA, Burton DR. Fc receptor but not complement binding is important in antibody protection against HIV. Nature 2007;449:101-104.
Forthal DN, Landucci G, Bream JH, Jacobson LP, Phan TB, Montoya B. Fc? Receptor IIa (Fc?RIIa) Genotype Predicts Progression of HIV Infection. J Immunol 2007;179:7916-23.
Eastman D, Piantadosi A, Wu X, Forthal DN, Landucci G, Kimata JT, Overbaugh J. Heavily glycosylated, highly fit SIVMne variants continue to diversify and undergo selection after transmission to a new host and they elicit early antibody dependent cellular responses but delayed neutralizing antibody responses. Virology J 2008;5:90.
Tomaras GD, Yates NL, Liu PH, Qin, Li, Fouda, GG, Chavez LL, Decamp AC, Parks RJ, Ashley VC, Lucas, JT, Cohen M, Eron J, Hicks CB, Liao H-X, Self SG, Landucci G, Forthal DN, Weinhold KJ, Keele BF, Hahn BH, Greenberg, ML, Morris L, Abdool Karim SS, Blattner WA, Montefiori DC, Shaw GM, Perelson AS, Haynes BF. Initial B Cell Responses 1 to Transmitted HIV-1: Virion-Binding IgM and IgG Antibodies Followed by Plasma Anti-gp41 Antibodies with Ineffective Control of Initial Viremia. J Virol 2008;82:12449-63.
Liu JY, O’Brien KL, Lynch DM, Simmons NL, La Porte A, Riggs AM, Abbink P, Coffey RT, Grandpre LE, Seaman MS, Landucci G, Forthal DN, Montefiori DC, Carville A, Mansfield KG, Havenga MJ, Pau MG, Goudsmit, Barouch DH. Immune control of an SIV challenge by a T cell-based vaccine in rhesus monkeys. Nature 2009;457:87-91.
Hessell AJ, Rakasz EG, Poignard P, Hangartner L, Landucci, G, Forthal DN, Koff WC, Watkins DI, Burton DR. Broadly Neutralizing Human Anti-HIV Antibody 2G12 is Effective in Protection Against Mucosal SHIV Challenge Even at Low Serum Neutralizing Titers. PLOS Pathogens 2009; 5: e1000433.
Forthal DN, Moog C. Fc receptor-mediated antiviral antibodies. Current Opin HIV AIDS. 2009;4:388-93. Invited review.
Barouch DN, Liu J, Lynch DM, O’Brien KL, La Porte A, Simmons NL, Riggs AM, Clark S, Abbink P, Montefiori DC, Landucci G, Forthal DN, Self SG, Carville A, Mansfield K, Goudsmit J. Protective efficacy of a single immunization of a chimeric adenovirus vector-based vaccine against SIV challenge in rhesus monkeys. J Virol 2009;83:9584-90.
Hessell AJ, Rakasz EG, Tehrani DM, Huber M, Weisgrau KL, Landucci G, Forthal DN, Koff WC, Poignard P, Watkins DI, Burton DR. Broadly neutralizing monoclonal antibodies 2F5 and 4E10, directed against the human immunodeficiency virus type 1 (HIV-1) gp41 membrane proximal external region (MPER), protect against SHIVBa-L mucosal challenge. J Virol 2010;84:1302-13.
Moody AM, Liao H-X, Alam SM, Scearce RM, Plonk MK, Kozink DM, Drinker MS, Xia S-M, Sutherland LL, Tomaras GD, Giles IP, Kappes JC, Ochsenbauer-Jambor C, Edmonds TG, Soares M, Barbero G, Forthal DN, Landucci G, Chang C, King SW, Kavlie A, Denny TN, Hwang K-K, Chen PP, Thorpe PE, Montefiori DC, Haynes BF. Anti-Phospholipid Human Monoclonal Antibodies Inhibit CCR5-Tropic HIV-1 and Induce ?-Chemokines. J Exp Med 2010;207:763-76.
Ng CT, Jaworski JP, Jayaraman P, Sutton WF, Delio P, Kuller L, Anderson D, Landucci G, Richardson BA, Burton DR, Forthal DN, Haigwood NL. Passive neutralizing antibody controls SHIV viremia and enhances B cell responses in infant macaques. Nature Med 2010;16:1117-9.
Forthal DN, Gach JS, Landucci G, Jakub J, Strasser R, Kunert R, Steinkellner H. Fc-glycosylation influences Fc? receptor binding and anti-HIV activity of monoclonal antibody 2G12. J Immunol 2010 185:6876-82.
Forthal DN, Landucci G, Ding H, Kappes JC, Wang A, Thung I, Phan TB. IgG2 inhibits HIV-1 internalization by monocytes, and IgG subclass binding is differentially affected by gp120 glycosylation. AIDS 2011;25:2099-104.
Bialuk I, Whitney S, Anresen V, Florese RH, Nacsa J, Cecchinato V, Valeri VW, Heraud J-M, Gordon S, Parks RW, Montefiori DC, Venzon D, Demberg T, Robert-Guroff M, Landucci G, Forthal DN, Franchini G. Vaccine-induced antibodies to the first variableloop of human immunodeficiency virus type 1 gp120 mediate antibody-dependent virus inhibition in macaques. Vaccine 2011;30:78-94.
Rasmussen RA, Siddappa NB, Lakhashe SK, Watkins J, Villinger F, Ibegbu C, Florese RH, Robert-Guroff M, Montefiori DC, Forthal DN, O’Connor D, Ruprecht RM. High-level, lasting antiviral immunity induced by a bimodal AIDS vaccine and boosted by live-virus exposure: prevention of viremia. AIDS 2012;26:149-55.
Barouch DH, Liu J, Maxfield LF, Abbink P, Lynch DM, Iampietro MJ, Seaman MS, Ferrari G, Forthal DN, Hirsch V, Carville A, Mansfield KG, Stablein D, Goudsmit J, Marovich MA, Robb ML, Kim JH, Michael NL. Distinct Correlates of Protection Against Acquisition and Virologic Control Following Heterologous SIVmac251 Challenge of Vaccinated Rhesus Monkeys. Nature 2012;482:89-93.
McBurney SP, Landucci G, Forthal DN, Ross TM. Protection against heterologous vaginal SHIV SF162p4 infection following vaccination with a polyvalent clade B virus-like particle vaccine. AIDS Res Hum Retrovirus 2012;28:1063-72.
Moldt B, Shibata-Koyama M, Rakasz EG, Schultz N, Kristian S, Kanda Y, Watanabe T, Dunlop DC, Finstad S, Landucci G, Albert MD, Dugast A-S, Parren PWHI, Evans DT, Alter G, Forthal DN, Schmitz JE, Iida S, Poignard P, Watkins DI, Hessell AJ, Burton DR. A non-fucosylated variant of the anti-HIV-1 MAb b12 hasFc?RIIIa-mediated antiviral activity in vitro but not improved protection against mucosal SHIV challenge in macaques. J Virol 2012;86:6189-96.
Forthal DN, Phan TB, Slepenkin AV, Landucci G, Chu H, Elofsson M, Peterson E. In vitro anti-HIV-1 activity of salicylidene acylhydrazide compounds that target sexually transmitted bacterial pathogens. Int J Antimicrob Agents 2012;40:354-60.
Van Rompay KKA, Trott KA, Jayashankar K, Geng Y, LaBranche CC, Johnson JA, Landucci G, Lipscomb J, Tarara RP, Canfield DR, Heneine W, Forthal DN, Montefiori D, Abel K. Prolonged tenofovir treatment of macaques infected with K65R reverse transcriptase mutants of SIV results in the development of antiviral immune responses that control virus replication after drug withdrawal. Retrovirology 2012;9:57.
Forthal DN, Gilbert PB, Wang A, Landucci G, Phan TB. Fc?RIIIa genotype and behavioral risk interact to predict HIV infection rate following recombinant gp120 vaccination. Blood 2012;120:2836-42.
Rosenberg Y, Sack M, Montefiori D, Forthal D, Mao L, Abanto SH, Urban L, Landucci G, Fischer R, Jiang X. Rapid High-Level Production of Functional HIV Broadly Neutralizing Monoclonal Antibodies in Transient Plant Expression Systems. PLoS One 2013;8:e58724.
Forthal DN, Landucci G, Chohan B, Richardson BA, McClelland RS, Jaoko W, Blish C, Overbaugh J. Antibody-dependent cell-mediated virus inhibition (ADCVI) antibody activity does not correlate with risk of HIV-1 superinfection. JAIDS 2013 (Epub ahead of print).
Watkins JD, Sholukh AM, Mukhtar MM, Siddappa NB, Lakhashe SK, Hemashettar G, Shanmuganathan V, Kim M, Reinherz EL, Gupta S, Forthal DN, Bachler B, Klein D, Rogers K, Kinsey K, Hu S-L, Agatic G, Corti D, Lanzavecchia A, Heeney JL, Sattentau Q, Weiss RA, Villinger F, Lee S, & Ruprecht RM. Anti-HIV-1 IgA Isotypes: Differential Virion Capture Linked to Blockage of Mucosal R5 SHIV Transmission. AIDS 2013;27:F13-20.
Vaccari M, Keele B, Bosinger S, Doster D, Ma Z-M, Pollara J, Hryniewicz A, Ferrari G, Guan YJ, Forthal D, Venzon D, Fenizia C, Morgan T, Montefiori D, Lifson J, Miller C, Silvestri G, Rosati M, Felber B, Pavlakis G, Tartaglia J, Franchini G. Protection afforded by an HIV vaccine candidate in macaques depends on the dose of SIVmac251 at challenge exposure. J Virol 2013;87:3538-48.
Jaworski JP, Kobie J, Brower Z, Malherbe DC, Landucci G, Sutton WF, Guo B, Reed J, Leon E, Engelmann F, Zheng B , Legasse A, Park B, Dickerson M , Lewis AD, Colgin LMA, Axthelm M, Messaoudi I, Sacha JB, Burton DR, Forthal DN, Hessell AJ, Haigwood NL. Neutralizing polyclonal IgG present during acute infection prevents rapid disease onset in SHIVSF162P3-infected infant rhesus macaques. J Virol 2013;87:10447-59.
Gorlani A, Forthal DN. Antibody-Dependent Enhancement and the Risk of HIV Infection. Current HIV Res 2013;11:421-6. (Invited review)
Gach JS, Quendler H, Tong T, Narayan KM, Du SX, Whalen RG, Binley JM, Forthal DN, Poignard P, Zwick MB. A human antibody to the CD4 binding site of gp120 capable of highly potent but sporadic cross clade neutralization of primary HIV-1. PLoS One 2013;8:e72054.
Forthal D, Hope TJ, Alter G. New paradigms for functional HIV-specific nonneutralizing antibodies. Curr Opin HIV AIDS 2013:8:392-400. Invited review)
Gupta S, Gach JS, Becerra JC, Phan TB, Pudney J, Moldoveanu Z, Joseph SB, Landucci G, Supnet MJ, Ping L-H; Corti D, Moldt D, Hel Z, Lanzavecchia A, Ruprecht RM, Burton DR, Mestecky J, Anderson DJ and Forthal DN. The neonatal Fc receptor (FcRn) enhances human immunodeficiency virus type 1 (HIV-1) transcytosis across epithelial cells. PLoS Pathogens 2013; 9:e1003776.
Gach JS, Achenbach CJ, Chromikova V, Berzins B, Lambert N, Landucci G, Forthal DN, Katlama C, Jung BH, Murphy RL. HIV-1 specific antibody titers and neutralization among chronically infected patients on long-term suppressive antiretroviral therapy (ART): a cross-sectional study. PLoS One 2014;9:e85371.
Sholukh AM, Siddappa NB, Shanmuganathan V, Hemashettar G, Lakhashe SK, Rasmussen RA, Watkins JD, Vyas HK, Thorat S, Brandstoetter T, Mukhtar MM, Yoon JK, Novembre FJ, Villinger F, Landucci G, Forthal DN, Ratcliffe R, Tuero I, Robert-Guroff M, Polonis VR, Bilska M, Montefiori DC, Johnson WE, Ertl HC, Ruprecht RM. Passive immunization of macaques with polyclonal anti-SHIV IgG against challenge with heterologous tier 2 SHIV: outcome depends on IgG dose. Retrovirology 2014;11:8.
|Grants||R01 AI102715 Forthal (PI) “The Impact of Antibody and pH on Female-toMale SIV Infection” 07/06/2012-06/30/2016|
|R01 AI090656 Forthal (PI) “Broadly Reactive Antibodies against Chimeric Virus-Host Antigens” 06/14/2010-05/31/2014|
Fellow, Infectious Diseases Society of America
American Society for Microbiology
|Research Centers||Center for Virus Research|
|Center for Immunology|
|Pacific-Southwest Center for Biodefense & Emerging Infectious Diseases|
|Link to this profile||http://www.faculty.uci.edu/profile.cfm?faculty_id=2934|