Antibodies and Infectious Disease
The perception of man as the easy victor over microbes has changed dramatically in the last two decades. Vaccination has offered protection against a number of viral pathogens, but it is increasingly recognized that the strategies used in the past will not be successful against all viruses. We are focused on developing rational vaccine strategies, particularly against HIV and particularly using an approach termed “Reverse Vaccinology 2.0”. In this approach, broadly neutralizing antibodies isolated from natural HIV infection are investigated in interaction with their sole viral target, the HIV Envelope, and the data used to guide immunogen design and immunization strategies. Immunogens are then evaluated in detail in animal models and the results used to iteratively improve immunogens as we move toward an HIV vaccine suitable to protect humans.
Hangartner L, Beauparlant D, Rakasz E, Nedellec R, Hozé N, McKenney K, Martins MA, Seabright GE, Allen JD, Weiler AM, Friedrich TC, Regoes RR, Crispin M, Burton DR. (2021) Effector function does not contribute to protection from virus challenge by a highly potent HIV broadly neutralizing antibody in nonhuman primates. Sci Transl Med. 13(585):eabe3349.
Conti S, Kaczorowski KJ, Song G, Porter K, Andrabi R, Burton DR, Chakraborty AK, Karplus M. (2021) Design of immunogens to elicit broadly neutralizing antibodies against HIV targeting the CD4 binding site. Proc Natl Acad Sci U S A. 118(9):e2018338118.
Rappazzo CG, Tse LV, Kaku CI, Wrapp D, Sakharkar M, Huang D, Deveau LM, Yockachonis TJ, Herbert AS, Battles MB, O’Brien CM, Brown ME, Geoghegan JC, Belk J, Peng L, Yang L, Hou Y, Scobey TD, Burton DR, Nemazee D, Dye JM, Voss JE, Gunn BM, McLellan JS, Baric RS, Gralinski LE, Walker LM. (2021) Broad and potent activity against SARS-like viruses by an engineered human monoclonal antibody. Science. 371(6531):823-829.
Rogers TF, Zhao F, Huang D, Beutler N, Burns A, He WT, Limbo O, Smith C, Song G, Woehl J, Yang L, Abbott RK, Callaghan S, Garcia E, Hurtado J, Parren M, Peng L, Ramirez S, Ricketts J, Ricciardi MJ, Rawlings SA, Wu NC, Yuan M, Smith DM, Nemazee D, Teijaro JR, Voss JE, Wilson IA, Andrabi R, Briney B, Landais E, Sok D, Jardine JG, Burton DR. (2020) Isolation of potent SARS-CoV-2 neutralizing antibodies and protection from disease in a small animal model. Science. 369(6506):956-963.
Wec AZ, Wrapp D, Herbert AS, Maurer DP, Haslwanter D, Sakharkar M, Jangra RK, Dieterle ME, Lilov A, Huang D, Tse LV, Johnson NV, Hsieh CL, Wang N, Nett JH, Champney E, Burnina I, Brown M, Lin S, Sinclair M, Johnson C, Pudi S, Bortz R 3rd, Wirchnianski AS, Laudermilch E, Florez C, Fels JM, O’Brien CM, Graham BS, Nemazee D, Burton DR, Baric RS, Voss JE, Chandran K, Dye JM, McLellan JS, Walker LM. (2020) Broad neutralization of SARS-related viruses by human monoclonal antibodies. Science. 369(6504):731-736.
Yuan M, Liu H, Wu NC, Lee CD, Zhu X, Zhao F, Huang D, Yu W, Hua Y, Tien H, Rogers TF, Landais E, Sok D, Jardine JG, Burton DR, Wilson IA. (2020) Structural basis of a shared antibody response to SARS-CoV-2. Science. 369(6507):1119-1123.