Current influenza vaccines mainly induce antibodies against the surface glycoprotein hemagglutinin (HA) that block viral attachment to its host receptors and viral membrane fusion to the host cell. The immunodominant head region of HA undergoes antigenic drift and antibodies directed to the head confer little cross-protections between strains or subtypes. Researchers at the Vaccine Research Center of the National Institute of Allergy and Infectious Diseases have identified human monoclonal antibodies that each bind distinct epitopes on the less abundant yet critical viral surface glycoprotein neuraminidase (NA). These antibodies, isolated from convalescent individuals with confirmed influenza A H3N2 infection, inhibit viral propagation of a wide range of human H3N2, swine-origin variant H3N2, and H2N2 viruses and confer pre-exposure and post-exposure protection from lethal H3N2 infection in mice. Cryo-electron microscopy revealed that two of these antibodies bind non-overlapping epitopes covering the underside of the NA head, thus defining a potential vaccine target. This technology is available for licensing for commercial development in accordance with 35 U.S.C. § 209 and 37 CFR part 404.