Development of broadly reactive influenza vaccines by targeting the conserved regions of the hemagglutinin stem and head domains

Introduction: Influenza virus infections cause serious illness in millions of people each year. Although influenza virus vaccines are available, they are not optimally effective due to mismatches between the influenza virus strains used for the vaccine and the circulating strains. To improve protection by vaccines, a broadly protective or universal vaccine may be required. Strategies to develop universal vaccines aim to elicit broadly reactive antibodies, which target regions on the viral hemagglutinin (HA) protein which are conserved between strains. Broadly reactive antibodies have helped to identify such targets and can guide the design of such a vaccine. Areas covered: The first part of this review provides an in-depth overview of broadly reactive anti-HA antibodies, discussing their origin, breadth and their mechanisms of protection. The second part discusses the technical design and mode of action of potential universal vaccine candidates that aim to elicit these broadly reactive antibodies and provide protection against a majority of influenza strains. Expert opinion: While great strides have been made in the development of universal influenza vaccine candidates, real-life use still requires improvement of stability, enhancement of their breadth of protection and ease of production, while efficacies need to be determined in human trials.