Structural Biology and the Design of Effective Vaccines for HIV-1 and Other Viruses

Kwong, Peter D.; Nabel, Gary J.; Acharya, Priyamvada; Boyington, Jeffrey C.; Chen, Lei; Hood, Chantelle; Kim, Albert; Kong, Leopold; Kwon, Young Do; Majeed, Shahzad; McLellan, Jason; Ofek, Gilad; Pancera, Marie; Sastry, Mallika; Changela, Anita; Stuckey, Jonathan; Zhou, Tongqing

Structural biology provides a wealth of information about the three-dimensional organization and chemical makeup of proteins. An understanding of atomic-level structure offers enormous potential to design rationally proteins that stimulate specific immune responses. Yet current vaccine development efforts makes little use of structural information. At the Vaccine Research Center, a major goal is to apply structural techniques to vaccine design for challenging pathogens, that include human immunodeficiency virus type 1 (HIV-1) and other enveloped viruses such as influenza, Ebola, and respiratory syncytial viruses. Our three-part strategy involves 1.) the definition of the functional viral spike at the atomic level 2.) achieving a structural understanding of how neutralizing antibodies recognize the spike, and 3.) rational development of proteins that can elicit a specific antibody response. Overall, our strategy aims to incorporate information about viral spike-antibody interactions, to assimilate immunogenic feedback, and to leverage recent advances in immunofocusing and computational biology.