Enhancing Neuraminidase Immunogenicity of Influenza A Viruses by Rewiring RNA Packaging Signals
| Autor: | Florian Krammer, Julia Peukes, Allen Zheng, Raffael Nachbagauer, John A. G. Briggs, Xiaoli Xiong, Shirin Strohmeier, Peter Palese, Alec W. Freyn, Weina Sun |
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| Rok vydání: | 2020 |
| Předmět: |
Gene Expression Regulation
Viral viruses Cross Protection Immunology Hemagglutinin (influenza) Gene Expression Neuraminidase Hemagglutinin Glycoproteins Influenza Virus Immunodominance Cross Reactions Antibodies Viral Microbiology Virus 03 medical and health sciences Mice Influenza A Virus H1N1 Subtype Orthomyxoviridae Infections Immunity Virology Influenza Human Vaccines and Antiviral Agents Animals Humans 030304 developmental biology 0303 health sciences Mice Inbred BALB C biology Influenza A Virus H5N1 Subtype 030306 microbiology Immunogenicity Influenza A Virus H3N2 Subtype Vaccination 3. Good health HEK293 Cells Hemagglutinins Influenza A virus Influenza Vaccines Insect Science biology.protein RNA Female Antibody |
| Zdroj: | J Virol Journal of Virology |
| ISSN: | 1098-5514 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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