Title: 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

Journal Article · · mBio (Online)
 [1];  [2];  [3]; ORCiD logo [4];  [5];  [5];  [5];  [6]; ORCiD logo [7];
  1. Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA, Department of Biotechnology, University of Natural Resources and Life Sciences, Vienna, Austria
  2. Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA, Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA
  3. Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, USA
  4. Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
  5. Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland, USA
  6. Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, USA, Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California, USA
  7. Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA, Department of Pathology, Molecular and Cell Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA

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.

Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Organization:
USDOE; USDOE Office of Science (SC), Basic Energy Sciences (BES)
Grant/Contract Number:
AC02-06CH11357
OSTI ID:
1832272
Journal Information:
mBio (Online), Journal Name: mBio (Online) Journal Issue: 6 Vol. 12; ISSN 2150-7511
Publisher:
American Society for MicrobiologyCopyright Statement
Country of Publication:
United States
Language:
English

References (62)

Mismatch between the 1997/1998 influenza vaccine and the major epidemic A(H3N2) virus strain as the cause of an inadequate vaccine-induced antibody response to this strain in the elderly journal May 2000
Divergent evolution of hemagglutinin and neuraminidase genes in recent influenza A:H3N2 viruses isolated in Canada journal July 2002
MolProbity: More and better reference data for improved all-atom structure validation: PROTEIN SCIENCE.ORG journal November 2017
Purified influenza A virus N2 neuraminidase vaccine is immunogenic and non-toxic in humans journal January 1995
Recombinant neuraminidase vaccine protects against lethal influenza journal April 1996
[20] Processing of X-ray diffraction data collected in oscillation mode book January 1997
Supplementation of conventional influenza A vaccine with purified viral neuraminidase results in a balanced and broadened immune response journal May 1998
Influenza Infection in Humans Induces Broadly Cross-Reactive and Protective Neuraminidase-Reactive Antibodies journal April 2018
Identification of Hemagglutinin Residues Responsible for H3N2 Antigenic Drift during the 2014–2015 Influenza Season journal July 2015
Structural Basis of Protection against H7N9 Influenza Virus by Human Anti-N9 Neuraminidase Antibodies journal December 2019
Development of recombinant protein-based influenza vaccine journal December 2006
Safety and immunogenicity of co-administration of meningococcal type A and measles–rubella vaccines with typhoid conjugate vaccine in children aged 15–23 months in Burkina Faso journal January 2021
Human Antibodies Targeting Influenza B Virus Neuraminidase Active Site Are Broadly Protective journal October 2020
Influenza neuraminidase antibodies provide partial protection for chickens against high pathogenic avian influenza infection journal May 2007
Randomized comparative study of the serum antihemagglutinin and antineuraminidase antibody responses to six licensed trivalent influenza vaccines journal December 2012
Correctly folded - but not necessarily functional - influenza virus neuraminidase is required to induce protective antibody responses in mice journal October 2020
Protection against a lethal H5N1 influenza challenge by intranasal immunization with virus-like particles containing 2009 pandemic H1N1 neuraminidase in mice journal October 2012
Advances in the development of influenza virus vaccines journal February 2015
The 2009 pandemic H1N1 neuraminidase N1 lacks the 150-cavity in its active site journal September 2010
Influenza journal June 2018
The human antibody response to influenza A virus infection and vaccination journal March 2019
H3N2 Mismatch of 2014–15 Northern Hemisphere Influenza Vaccines and Head-to-head Comparison between Human and Ferret Antisera derived Antigenic Maps journal October 2015
Discordant antigenic drift of neuraminidase and hemagglutinin in H1N1 and H3N2 influenza viruses journal December 2011
Antigen-presenting B cells and helper T cells cooperatively mediate intravirionic antigenic competition between influenza A virus surface glycoproteins. journal October 1987
Independent and disparate evolution in nature of influenza A virus hemagglutinin and neuraminidase glycoproteins. journal January 1990
Immunization with purified N1 and N2 influenza virus neuraminidases demonstrates cross-reactivity without antigenic competition. journal March 1994
Assembly of Subtype 1 Influenza Neuraminidase Is Driven by Both the Transmembrane and Head Domains journal January 2013
Protection of Mice with Recombinant Influenza Virus Neuraminidase journal February 2004
Impact of Influenza B Lineage-Level Mismatch Between Trivalent Seasonal Influenza Vaccines and Circulating Viruses, 1999–2012 journal August 2014
Pre-existing Antineuraminidase Antibodies Are Associated With Shortened Duration of Influenza A(H1N1)pdm Virus Shedding and Illness in Naturally Infected Adults journal July 2019
Induction of Partial Immunity to Influenza by a Neuraminidase-specific Vaccine journal April 1974
Clinical and Immunologic Evaluation of NeuraminidaseSpecific Influenza A Virus Vaccine in Humans journal April 1977
Antibody Correlates and Predictors of Immunity to Naturally Occurring Influenza in Humans and the Importance of Antibody to the Neuraminidase journal January 2013
Antibody to Influenza Virus Neuraminidase: An Independent Correlate of Protection journal April 2015
A conserved leucine zipper-like motif accounts for strong tetramerization capabilities of SEPALLATA-like MADS-domain transcription factors journal February 2018
Likelihood-enhanced fast translation functions journal March 2005
PHENIX: a comprehensive Python-based system for macromolecular structure solution journal January 2010
Features and development of Coot journal March 2010
Refinement of Macromolecular Structures by the Maximum-Likelihood Method journal May 1997
Broadly protective human antibodies that target the active site of influenza virus neuraminidase journal October 2019
Structure of the Tetramerization Domain of Measles Virus Phosphoprotein journal April 2013
Cross-Reactive Neuraminidase-Inhibiting Antibodies Elicited by Immunization with Recombinant Neuraminidase Proteins of H5N1 and Pandemic H1N1 Influenza A Viruses journal May 2015
Structural Characterization of the 1918 Influenza Virus H1N1 Neuraminidase journal August 2008
Molecular Basis for Broad Neuraminidase Immunity: Conserved Epitopes in Seasonal and Pandemic H1N1 as Well as H5N1 Influenza Viruses journal June 2013
Dissociation of influenza virus hemagglutinin and neuraminidase eliminates their intravirionic antigenic competition journal October 1993
Evaluation of Antihemagglutinin and Antineuraminidase Antibodies as Correlates of Protection in an Influenza A/H1N1 Virus Healthy Human Challenge Model journal April 2016
Mucosal Immunity against Neuraminidase Prevents Influenza B Virus Transmission in Guinea Pigs journal May 2019
Analysis of Anti-Influenza Virus Neuraminidase Antibodies in Children, Adults, and the Elderly by ELISA and Enzyme Inhibition: Evidence for Original Antigenic Sin journal May 2017
NAction! How Can Neuraminidase-Based Immunity Contribute to Better Influenza Virus Vaccines? journal April 2018
Vaccination with Adjuvanted Recombinant Neuraminidase Induces Broad Heterologous, but Not Heterosubtypic, Cross-Protection against Influenza Virus Infection in Mice journal March 2015
Antibodies to the Glycoprotein GP2 Subunit Cross-React between Old and New World Arenaviruses journal May 2018
Influenza A penetrates host mucus by cleaving sialic acids with neuraminidase journal January 2013
Cross-Reactive Neuraminidase Antibodies Afford Partial Protection against H5N1 in Mice and Are Present in Unexposed Humans journal February 2007
A Contributing Role for Anti-Neuraminidase Antibodies on Immunity to Pandemic H1N1 2009 Influenza A Virus journal October 2011
A Carboxy-Terminal Trimerization Domain Stabilizes Conformational Epitopes on the Stalk Domain of Soluble Recombinant Hemagglutinin Substrates journal August 2012
Low 2012–13 Influenza Vaccine Effectiveness Associated with Mutation in the Egg-Adapted H3N2 Vaccine Strain Not Antigenic Drift in Circulating Viruses journal March 2014
A Beneficiary Role for Neuraminidase in Influenza Virus Penetration through the Respiratory Mucus journal October 2014
Paradoxical clade- and age-specific vaccine effectiveness during the 2018/19 influenza A(H3N2) epidemic in Canada: potential imprint-regulated effect of vaccine (I-REV) journal November 2019
Influenza Virus Neuraminidase Structure and Functions journal January 2019
In the Shadow of Hemagglutinin: A Growing Interest in Influenza Viral Neuraminidase and Its Role as a Vaccine Antigen journal June 2014
Introduction of Cysteines in the Stalk Domain of Recombinant Influenza Virus N1 Neuraminidase Enhances Protein Stability and Immunogenicity in Mice journal April 2021
Expression of Functional Recombinant Hemagglutinin and Neuraminidase Proteins from the Novel H7N9 Influenza Virus Using the Baculovirus Expression System journal January 2013