title: Influenza virus-specific neutralizing IgM antibodies persist for a lifetime.
abstract: Detection of immunoglobulin M (IgM) antibodies has long been used as an important diagnostic tool for identifying active viral infections, but their relevance in later stages has not been clearly defined in vivo. In this study, we followed the kinetics, longevity, and function of influenza virus-specific IgM antibodies for 2 years following sublethal infection of mice with live mouse-adapted A/PR/8/34 virus or immunization with formalin-inactivated virus. These groups mounted robust protective immune responses and survived lethal challenges with 50 × 50% lethal dose (LD50) mouse-adapted A/PR/8/34 virus 600 days after the primary exposure. Surprisingly, the virus-specific IgM antibodies persisted along with IgG antibodies, and we found a significantly higher number of IgM-positive (IgM(+)) virus-specific plasma cells than IgG(+) plasma cells that persisted for at least 9 months postexposure. The IgM antibodies were functional as they neutralized influenza virus in the presence of complement just as well as IgG antibodies did.
authors.affiliation: Department of Microbiology and Immunology, Emory University Medical School and Emory Vaccine Center, Atlanta, Georgia, USA.
authors.forename: Ioanna
authors.initials: I
authors.lastname: Skountzou
authors.affiliation: Department of Microbiology and Immunology, Emory Vaccine Center, Yerkes National Primate Center, Emory University, Atlanta, Georgia, USA.
authors.forename: Lakshmipriyadarshini
authors.initials: L
authors.lastname: Satyabhama
authors.affiliation: Department of Microbiology and Immunology, Department of Microbiology, Medical School, University of Athens, Athens, Greece.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Stavropoulou
authors.affiliation: Department of Microbiology and Immunology, Emory University Medical School and Emory Vaccine Center, Atlanta, Georgia, USA.
authors.forename: Zuhha
authors.initials: Z
authors.lastname: Ashraf
authors.affiliation: Department of Microbiology and Immunology, Emory University Medical School and Emory Vaccine Center, Atlanta, Georgia, USA.
authors.forename: E Stein
authors.initials: ES
authors.lastname: Esser
authors.affiliation: Department of Microbiology and Immunology, Emory University Medical School and Emory Vaccine Center, Atlanta, Georgia, USA.
authors.forename: Elena
authors.initials: E
authors.lastname: Vassilieva
authors.affiliation: Department of Microbiology and Immunology, Emory University Medical School and Emory Vaccine Center, Atlanta, Georgia, USA.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Koutsonanos
authors.affiliation: Department of Microbiology and Immunology, Emory University Medical School and Emory Vaccine Center, Atlanta, Georgia, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Compans
authors.affiliation: Department of Microbiology and Immunology, Emory Vaccine Center, Yerkes National Primate Center, Emory University, Atlanta, Georgia, USA joshy.jacob@emory.edu.
authors.forename: Joshy
authors.initials: J
authors.lastname: Jacob
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood*; D003165:Complement System Proteins / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D007075:Immunoglobulin M / Q000097:blood*; D009980:Influenza A virus / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D009976:Orthomyxoviridae Infections / Q000517:prevention & control*; D010950:Plasma Cells / Q000276:immunology; D016019:Survival Analysis; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D007075:Immunoglobulin M; D007252:Influenza Vaccines; D015164:Vaccines, Inactivated; D003165:Complement System Proteins