Enhancing neuraminidase immunogenicity of influenza a viruses by rewiring RNA packaging signals

Allen Zheng, Weina Sun, Xiaoli Xiong, Alec W. Freyn, Julia Peukes, Shirin Strohmeier, Raffael Nachbagauer, John A.G. Briggs, Florian Krammer, Peter Palese

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


Humoral immune protection against influenza virus infection is mediated largely by antibodies against hemagglutinin (HA) and neuraminidase (NA), the two major glycoproteins on the virus surface. While influenza virus vaccination efforts have focused mainly on HA, NA-based immunity has been shown to reduce disease severity and provide heterologous protection. Current seasonal vaccines do not elicit strong anti-NA responses—in part due to the immunodominance of the HA protein. Here, we demonstrate that by swapping the 5= and 3= terminal packaging signals of the HA and NA genomic segments, which contain the RNA promoters, we are able to rescue influenza viruses that express more NA and less HA. Vaccination with formalin-inactivated “rewired” viruses significantly enhances the anti-NA antibody response compared to vaccination with unmodified viruses. Passive transfer of sera from mice immunized with rewired virus vaccines shows better protection against influenza virus challenge. Our results provide evidence that the immunodominance of HA stems in part from its abundance on the viral surface, and that rewiring viral packaging signals—thereby increasing the NA content on viral particles—is a viable strategy for improving the immunogenicity of NA in an influenza virus vaccine. IMPORTANCE Influenza virus infections are a major source of morbidity and mortality worldwide. Increasing evidence highlights neuraminidase as a potential vaccination target. This report demonstrates the efficacy of rewiring influenza virus packaging signals for creating vaccines with more neuraminidase content which provide better neuraminidase (NA)-based protection.

Original languageEnglish
Article numbere01227-20
JournalJournal of Virology
Issue number16
StatePublished - 1 Aug 2020


  • Immunodominance
  • Influenza
  • Neuraminidase
  • Packaging signal
  • Vaccine


Dive into the research topics of 'Enhancing neuraminidase immunogenicity of influenza a viruses by rewiring RNA packaging signals'. Together they form a unique fingerprint.

Cite this