A Novel Recombinant Influenza Virus Neuraminidase Vaccine Candidate Stabilized by a Measles Virus Phosphoprotein Tetramerization Domain Provides Robust Protection from Virus Challenge in the Mouse Model
Deming, Meagan E
Pasetti, Marcela F
Neuzil, Kathleen M
Wilson, Ian A
PublisherAmerican Society for Microbiology
MetadataShow full item record
AbstractCurrent seasonal influenza virus vaccines do not induce robust immune responses to neuraminidase. Several factors, including immunodominance of hemagglutinin over neuraminidase, instability of neuraminidase in vaccine formulations, and variable, nonstandardized amounts of neuraminidase in the vaccines, may contribute to this effect. However, vaccines that induce strong antineuraminidase immune responses would be beneficial, as they are highly protective. Furthermore, antigenic drift is slower for neuraminidase than for hemagglutinin, potentially providing broader coverage. Here, we designed stabilized recombinant versions of neuraminidase by replacing the N-terminal cytoplasmic domain, transmembrane, and extracellular stalk with tetramerization domains from the measles or Sendai virus phosphoprotein or from an Arabidopsis thaliana transcription factor. The measles virus tetramerization domain-based construct, termed N1-MPP, was chosen for further evaluation, as it retained antigenicity, neuraminidase activity, and structural integrity and provided robust protection in vivo against lethal virus challenge in the mouse model. We tested N1-MPP as a standalone vaccine, admixed with seasonal influenza virus vaccines, or given with seasonal influenza virus vaccines but in the other leg of the mouse. Admixture with different formulations of seasonal vaccines led to a weak neuraminidase response, suggesting a dominant effect of hemagglutinin over neuraminidase when administered in the same formulation. However, administration of neuraminidase alone or with seasonal vaccine administered in the alternate leg of the mouse induced robust antibody responses. Thus, this recombinant neuraminidase construct is a promising vaccine antigen that may enhance and broaden protection against seasonal influenza viruses. IMPORTANCE Influenza virus infections remain a high risk to human health, causing up to 650,000 deaths worldwide every year, with an enormous burden on the health care system. Since currently available seasonal vaccines are only partially effective and often mismatched to the circulating strains, a broader protective influenza virus vaccine is needed. Here, we generated a recombinant influenza virus vaccine candidate based on the more conserved neuraminidase surface glycoprotein in order to induce a robust and broader protective immune response against a variety of circulating influenza virus strains.
Identifier to cite or link to this itemhttp://hdl.handle.net/10713/17222
- Vaccination with Recombinant Parainfluenza Virus 5 Expressing Neuraminidase Protects against Homologous and Heterologous Influenza Virus Challenge.
- Authors: Mooney AJ, Gabbard JD, Li Z, Dlugolenski DA, Johnson SK, Tripp RA, He B, Tompkins SM
- Issue date: 2017 Dec 1
- Neuraminidase-Inhibiting Antibody Titers Correlate with Protection from Heterologous Influenza Virus Strains of the Same Neuraminidase Subtype.
- Authors: Walz L, Kays SK, Zimmer G, von Messling V
- Issue date: 2018 Sep 1
- Influenza Neuraminidase Characteristics and Potential as a Vaccine Target.
- Authors: Creytens S, Pascha MN, Ballegeer M, Saelens X, de Haan CAM
- Issue date: 2021
- A viable recombinant rhabdovirus lacking its glycoprotein gene and expressing influenza virus hemagglutinin and neuraminidase is a potent influenza vaccine.
- Authors: Ryder AB, Buonocore L, Vogel L, Nachbagauer R, Krammer F, Rose JK
- Issue date: 2015 Mar
- Extending the Stalk Enhances Immunogenicity of the Influenza Virus Neuraminidase.
- Authors: Broecker F, Zheng A, Suntronwong N, Sun W, Bailey MJ, Krammer F, Palese P
- Issue date: 2019 Sep 15