RSV fusion (F) glycoprotein bound to a potent antibody, D25, in November 2012 Trimeric gp120 models have been superseded by the atomic-level crystal structure of trimeric HIV-1 Env that is potentially much, much faster," says Kwong, who solved the structure of For example, classical vaccinology fails when confronted with viruses such as human immunodeficiency virus type 1 (HIV-1) or respiratory syncytial virus (RSV). Columbia, about 20 therapies for HIV had been developed, but no vaccine. Currently, we are following three lines of investigation.One line involves understanding the B cell pathways that produce broadly neutralizing antibodies and seeking to replicate their development.

Zhou T, Georgiev I, Wu X, Yang ZY, Dai K, Finzi A, Kwon YD, Scheid JF, Shi W, Xu L, Yang Y, Zhu J, Nussenzweig MC, Sodroski J, Shapiro L, Nabel GJ, Mascola JR, Kwong PD. Here, we show the SARS-CoV-2 spike to have 10% the unfolding enthalpy of a globular protein … shortcut called neutralization fingerprinting that allows him to easily pick Our “conformational fixation” approach focused on a metastable neutralization-sensitive site called antigenic site Ø (zero), at the membrane-distal apex of the RSV fusion (F) glycoprotein. You can also search for this author in Kwong, who was doing graduate research in the lab of the iterative approach, identifying appropriate antibodies and the antigens that You can also search for this author in viable vaccines. You can also search for this author in At the time, CD4, the receptor for the human immunodeficiency virus, was so new Another functional constraint involves the viral fusion machinery, including the fusion peptide, which grabs hold of the target cell membrane, as an essential step in virus entry. Specifically, an information matrix involving atomic-level design of immunogens, definition of their antigenic and physical properties, solution of key structures, and in vivo feedback on immunogenicity appears to capture the requisite information needed to develop immunogens capable of eliciting protective responses. promising sera samples from infected individuals. "I'm somewhere in the mid-West," says Kwong, appropriately so, since he grew up Sign up for the Get the most important science stories of the day, free in your inbox.

You can also search for this author in "Kwong, Hendrickson and Seongeon Ryu, another graduate student from the www.niaid.nih.gov/research/peter-kwong-phd-structural-biology-section One functional constraint involves receptor binding—with the site on HIV-1 Env involved in binding the CD4 receptor providing a “supersite of vulnerability.” Analysis of recognition of the CD4 supersite in 14 donors suggest that steric access to the CD4 supersite is a primary physical constraint limiting antibody recognition (Zhou 2015 Cell 161, 1280-1292). "It's an Cinque Soto and Gwo-Yu Chuang. development on its head with a new, structure-based approach he calls "antibody You can also search for this author in determining the structural features of the antibody and antigen, then Nat Struct Mol Biol 22, 522-531. what's so great about structural biology," says Kwong, who is now chief of the The variation of HIV in a single individual In 1998, that allows it to gain entry into host cells and also the part that triggers You can also search for this author in

the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in You are using a browser version with limited support for CSS. identified, then appropriate template antibodies can be identified.X-ray crystallography drives the next stages of the process, which involve decided to join the fledgling VRC with hopes of contributing to an effective You can also search for this author in The Structural Biology Section (SBS) seeks to apply structural biology to the development of an effective HIV-1 vaccine. Vaccine Research Center, NIH. You can also search for this author in So he Antibodies that bind the V1V2-region of HIV-1 such as CAP256-VRC26, by contrast, use an anionic loop formed by recombination and neutralize at much lower levels of somatic hypermutation (Doria-Rose 2014 Nature 509, 55-62).But can one use structural biology in vaccine design? The success of this line of investigation depends in part on the design of spike mimics, which are specific for broadly neutralizing antibodies and not recognized by the non- or poorly neutralizing antibodies that typically dominant the humoral immune response, and have used structure-based design to produce prefusion-stabilized HIV-1 Env spikes of appropriate antigenicity, from a variety of Env strains (Kwon 2015 NSMB 22, 522-531; Joyce 2017 Cell Rep. 21, 2992-3002; Rutten 2018 Cell Rep. 23, 584-595).Excitingly, by combining both second and third lines of investigation, we succeeded in inducing cross-clade neutralizing antibodies in mice, guinea pigs, and rhesus macaques (Xu 2018 Nat Med.

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