Research Article

A stable trimeric influenza hemagglutinin stem as a broadly protective immunogen

See allHide authors and affiliations

Science  24 Aug 2015:
aac7263
DOI: 10.1126/science.aac7263

You are currently viewing the abstract.

View Full Text

Abstract

The identification of human broadly neutralizing antibodies (bnAbs) targeting the hemagglutinin (HA) stem revitalized hopes of developing a universal influenza vaccine. Using a rational design and library approach, we engineered stable HA stem antigens (‘mini-HAs’) based on an H1 subtype sequence. Our most advanced candidate exhibits structural and bnAb binding properties comparable to full-length HA, completely protects mice in lethal heterologous and heterosubtypic challenge models, and reduces fever following sublethal challenge in cynomolgus monkeys. Antibodies elicited by this mini-HA in mice and nonhuman primates bind a wide range of HAs, compete with human bnAbs for HA stem binding, neutralize H5N1 viruses, and mediate antibody-dependent effector activity. These results provide proof-of-concept for design of HA stem mimics that elicit bnAbs against influenza A group 1 viruses.

View Full Text