Influenza hemagglutinin stem-fragment immunogen elicits broadly neutralizing antibodies and confers heterologous protection

• DOI: 10.1073/pnas.1402766111
• Publication Date: 2014-06-10T07:46:19Z
• Authors: Vamsee V. A. Mall...; Michael Citron; Francesca Ferrara; Xianghan Lu; Cheryl Callahan; Gwendolyn J. Heid...; Siddhartha P. Sarma; Jessica A. Flynn; Nigel J. Temperton; Xiaoping Liang; Raghavan Varadarajan
• Keywords: Immunogen; Heterologous

Significance Hemagglutinin (HA), the major influenza virus envelope glycoprotein, is principal target of neutralizing antibodies. Wide diversity and variation HA entails annual vaccination, as current vaccines typically fail to elicit/boost cross-reactive, broadly antibodies (bnAbs). Although several bnAbs bind at conserved stem making it an attractive universal vaccine candidate, metastable conformation this domain imposes challenges in designing a stable, independently folding immunogen. We rationally designed stem-fragment immunogen, mimicking native that binds conformation-specific with high affinity. The immunogen elicited conferred robust protection against lethal, heterologous challenge vivo. Additionally, soluble bacterial expression such thermotolerant, disulfide-free allows for rapid scale-up during pandemic outbreak.