A stable trimeric influenza hemagglutinin stem as a broadly protective immunogen
Science, 2015•science.org
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 those of full-length HA, completely protects mice
in lethal heterologous and heterosubtypic challenge models, and reduces fever after …
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 those of full-length HA, completely protects mice
in lethal heterologous and heterosubtypic challenge models, and reduces fever after …
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 those of full-length HA, completely protects mice in lethal heterologous and heterosubtypic challenge models, and reduces fever after sublethal challenge in cynomolgus monkeys. Antibodies elicited by this mini-HA in mice and nonhuman primates bound a wide range of HAs, competed with human bnAbs for HA stem binding, neutralized H5N1 viruses, and mediated antibody-dependent effector activity. These results represent a proof of concept for the design of HA stem mimics that elicit bnAbs against influenza A group 1 viruses.
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