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.
Steichen JM, Kulp DW, Tokatlian T, Escolano A, Dosenovic P, Stanfield RL, McCoy LE, Ozorowski G, Hu X, Kalyuzhniy O, Briney B, Schiffner T, Garces F, Freund NT, Gitlin AD, Menis S, Georgeson E, Kubitz M, Adachi Y, Jones M, Mutafyan AA, Yun DS, Mayer CT, Ward AB, Burton DR, Wilson IA, Irvine DJ, Nussenzweig MC, Schief WR. 2016. HIV vaccine design to target germline precursors of glycan-dependent broadly neutralizing antibodies. Immunity. In Press.
Briney B, Sok D, Jardine JG, Kulp DW, Skog P, Menis S, Jacak R, Kalyuzhniy O, de Val N, Sesterhenn F, Le KM, Ramos A, Jones M, Saye-Francisco KL, Blane TR, Spencer S, Georgeson E, Hu X, Ozorowski G, Adachi Y, Kubitz M, Sarkar A, Wilson IA, Ward AB, Nemazee D, Burton DR, Schief WR. 2016. Tailored immunogens direct affinity maturation toward HIV neutralizing antibodies. Cell. 166:1459-70.
Sok D, Briney B, Jardine JG, Kulp DW, Menis S, Pauthner M, Wood A, Lee EC, Le KM, Jones M, Ramos A, Kalyuzhniy O, Adachi Y, Kubitz M, MacPherson S, Bradley A, Friedrich GA, Schief WR, Burton DR. 2016. Priming HIV-1 broadly neutralizing antibody precursors in human Ig loci transgenic mice. Science. In Press.
McCoy LE, van Gils MJ, Ozorowski G, Messmer T, Briney B, Voss JE, Kulp DW, Macauley MS, Sok D, Pauthner M, Menis S, Cottrell CA, Torres JL, Hsueh J, Schief WR, Wilson IA, Ward AB, Sanders RW, Burton DR. 2016. Holes in the Glycan Shield of the Native HIV Envelope Are a Target of Trimer-Elicited Neutralizing Antibodies. Cell Rep. 16:2327-38.