title: Influenza virus vaccine based on the conserved hemagglutinin stalk domain.
abstract: Although highly effective in the general population when well matched to circulating influenza virus strains, current influenza vaccines are limited in their utility due to the narrow breadth of protection they provide. The strain specificity of vaccines presently in use mirrors the exquisite specificity of the neutralizing antibodies that they induce, that is, antibodies which bind to the highly variable globular head domain of hemagglutinin (HA). Herein, we describe the construction of a novel immunogen comprising the conserved influenza HA stalk domain and lacking the globular head. Vaccination of mice with this headless HA construct elicited immune sera with broader reactivity than those obtained from mice immunized with a full-length HA. Furthermore, the headless HA vaccine provided full protection against death and partial protection against disease following lethal viral challenge. Our results suggest that the response induced by headless HA vaccines is sufficiently potent to warrant their further development toward a universal influenza virus vaccine.
authors.affiliation: Department of Microbiology, Mount Sinai School of Medicine, New York, New York, USA.
authors.forename: John
authors.initials: J
authors.lastname: Steel
authors.forename: Anice C
authors.initials: AC
authors.lastname: Lowen
authors.forename: Taia T
authors.initials: TT
authors.lastname: Wang
authors.forename: Mark
authors.initials: M
authors.lastname: Yondola
authors.forename: Qinshan
authors.initials: Q
authors.lastname: Gao
authors.forename: Kester
authors.initials: K
authors.lastname: Haye
authors.forename: Adolfo
authors.initials: A
authors.lastname: García-Sastre
authors.forename: Peter
authors.initials: P
authors.lastname: Palese