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.
Andrabi R, Pallesen J, Allen JD, Song G, Zhang J, de Val N, Gegg G, Porter K, Su CY, Pauthner M, Newman A, Bouton-Verville H, Garces F, Wilson IA, Crispin M, Hahn BH, Haynes BF, Verkoczy L, Ward AB, Burton DR. (2019) The Chimpanzee SIV Envelope Trimer: Structure and Deployment as an HIV Vaccine Template. Cell Rep. 27(8):2426-2441.
Pauthner MG, Nkolola JP, Havenar-Daughton C, Murrell B, Reiss SM, Bastidas R, Prévost J, Nedellec R, von Bredow B, Abbink P, Cottrell CA, Kulp DW, Tokatlian T, Nogal B, Bianchi M, Li H, Lee JH, Butera ST, Evans DT, Hangartner L, Finzi A, Wilson IA, Wyatt RT, Irvine DJ, Schief WR, Ward AB, Sanders RW, Crotty S, Shaw GM, Barouch DH, Burton DR. (2019) Vaccine-Induced Protection from Homologous Tier 2 SHIV Challenge in Nonhuman Primates Depends on Serum-Neutralizing Antibody Titers. Immunity. 50(1):241-252.
Bianchi M, Turner HL, Nogal B, Cottrell CA, Oyen D, Pauthner M, Bastidas R, Nedellec R, McCoy LE, Wilson IA, Burton DR, Ward AB, Hangartner L. Electron-microscopy-based epitope mapping defines specificities of polyclonal antibodies elicited during HIV-1 BG505 envelope trimer immunization. Immunity. 49(2):288-300.
Landais E, Murrell B, Briney B, Murrell S, Rantalainen K, Berndsen ZT, Ramos A, Wickramasinghe L, Smith ML, Eren K, de Val N, Wu M, Cappelletti A, Umotoy J, Lie Y, Wrin T, Algate P, Chan-Hui PY, Karita E; IAVI Protocol C Investigators; IAVI African HIV Research Network, Ward AB, Wilson IA, Burton DR, Smith D, Pond SLK, Poignard P. (2017) HIV Envelope Glycoform Heterogeneity and Localized Diversity Govern the Initiation and Maturation of a V2 Apex Broadly Neutralizing Antibody Lineage. Immunity. 47(5):990-1003.