Duke University

The United States of America, as Represented by the Secretary, Department of Health and Human Services

Children's Medical Center Corporation

Leland Stanford Junior University

University of Pennsylvania

Boston University

Los Alamos National Security, LLC

Triad National Security, LLC

Thomas B Kepler

Barton F Haynes

Hua-Xin Liao

Stephen C Harrison

Peter D Kwong

John R Mascola

Bette T Korber

Tongqing Zhou

Beatrice H Hahn

George M Shaw

Feng Gao

Garnett Kelsoe

Scott D Boyd

Rebecca M Lynch

Peter Kwong

Gary J Nabel

John Mascola

Xueling Wu

M Anthony Moody

James Whittle

Aaron G Schmidt

Scott Boyd

The present invention relates, in general, to HIV-1 and, in particular, to broadly neutralizing HIV-1 antibodies, and to HIV-1 immunogens and to methods of using such immunogens to induce the production of broadly neutralizing HIV-1 antibodies in a subject (e.g., a human).

Antibody evolution immunogens

The present invention relates, in general, to an HIV-1 vaccine and, in particular, to a B cell lineage-based vaccination protocol.

Methods to identify prime and boost immunogens for use in a B cell lineage-based vaccination protocol

Antibody VRC01 represents a human immunoglobulin that neutralizes&#x2014;&#x2dc;90% of diverse HIV-1 isolates. To understand how such broadly neutralizing HIV-1 antibodies develop and recognize the viral envelope, we used X-ray crystallography and 454 pyrosequencing to characterize additional antibodies from HIV-1-infected individuals. Crystal structures revealed a convergent mode of binding of different antibodies to the same CD4-binding-site epitope. Antibody recognition was achieved through the evolution of complementary contact domains that were generated in diverse ways. Phylogenetic analysis of expressed heavy and light chains determined by deep sequencing revealed a common pathway of antibody heavy chain maturation confined to IGHV1-2*02 lineage that could pair with different light chains. The maturation pathway inferred by antibodyomics reveals that diverse antibodies evolve to a highly affinity-matured state to recognize an invariant viral structure, providing insight into the development and evolution of broadly neutralizing HIV-1 immunity.

Focused evolution of HIV-1 neutralizing antibodies revealed by crystal structures and deep sequencing

GP120 immunogens and methods inducing neutralizing antibodies to human immunodeficiency virus

The invention features a novel influenza antibody that specifically binds to influenza hemagglutinin and reduces or inhibits hemagglutinin binding to sialic acid. The invention also provides methods, compositions, and kits featuring the novel antibody and its use in preventing or treating influenza infection.

Broadly neutralizing human antibody that recognizes the receptor-binding pocket of influenza hemagglutinin

Growing community of inventors

Boston, MA, United States of America

Thomas B Kepler