title: Canine distemper virus neutralization activity is low in human serum and it is sensitive to an amino acid substitution in the hemagglutinin protein.
abstract: Serum was analyzed from 146 healthy adult volunteers in eastern Africa to evaluate measles virus (MV) and canine distemper virus (CDV) neutralizing antibody (nAb) prevalence and potency. MV plaque reduction neutralization test (PRNT) results indicated that all sera were positive for MV nAbs. Furthermore, the 50% neutralizing dose (ND50) for the majority of sera corresponded to antibody titers induced by MV vaccination. CDV nAbs titers were low and generally were detected in sera with high MV nAb titers. A mutant CDV was generated that was less sensitive to neutralization by human serum. The mutant virus genome had 10 nucleotide substitutions, which coded for single amino acid substitutions in the fusion (F) and hemagglutinin (H) glycoproteins and two substitutions in the large polymerase (L) protein. The H substitution occurred in a conserved region involved in receptor interactions among morbilliviruses, implying that this region is a target for cross-reactive neutralizing antibodies.
authors.affiliation: AIDS Vaccine Design and Development Laboratory, International AIDS Vaccine Initiative (IAVI), Brooklyn, NY, USA; Molecular and Cellular Biology Program, State University of New York, Brooklyn, NY, USA. Electronic address: xzhang@iavi.org.
authors.forename: Xinsheng
authors.initials: X
authors.lastname: Zhang
authors.affiliation: AIDS Vaccine Design and Development Laboratory, International AIDS Vaccine Initiative (IAVI), Brooklyn, NY, USA.
authors.forename: Olivia L
authors.initials: OL
authors.lastname: Wallace
authors.affiliation: AIDS Vaccine Design and Development Laboratory, International AIDS Vaccine Initiative (IAVI), Brooklyn, NY, USA.
authors.forename: Arban
authors.initials: A
authors.lastname: Domi
authors.affiliation: AIDS Vaccine Design and Development Laboratory, International AIDS Vaccine Initiative (IAVI), Brooklyn, NY, USA.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Wright
authors.affiliation: AIDS Vaccine Design and Development Laboratory, International AIDS Vaccine Initiative (IAVI), Brooklyn, NY, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Driscoll
authors.affiliation: Kenya AIDS Vaccine Initiative (KAVI)-Institute of Clinical Research, Nairobi, Kenya.
authors.forename: Omu
authors.initials: O
authors.lastname: Anzala
authors.affiliation: Centre for Geographic Medicine Research, Kenya Medical Research Institute (KEMRI), Kilifi, Kenya & Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Headington, UK.
authors.forename: Eduard J
authors.initials: EJ
authors.lastname: Sanders
authors.affiliation: MRC/UVRI Uganda Virus Research Unit on AIDS, Masaka and Entebbe, Uganda.
authors.forename: Anatoli
authors.initials: A
authors.lastname: Kamali
authors.affiliation: Projet San Francisco, Kigali, Rwanda.
authors.forename: Etienne
authors.initials: E
authors.lastname: Karita
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Allen
authors.affiliation: Department of Medical Affairs, International AIDS Vaccine Initiative, NY, NY, USA.
authors.forename: Pat
authors.initials: P
authors.lastname: Fast
authors.affiliation: Human Immunology Laboratory, International AIDS Vaccine Initiative, London, UK.
authors.forename: Jill
authors.initials: J
authors.lastname: Gilmour
authors.affiliation: Department of Medical Affairs, International AIDS Vaccine Initiative, NY, NY, USA; Department of Epidemiology and Biostatistics, University of California at San Francisco, San Francisco, CA, USA.
authors.forename: Matt A
authors.initials: MA
authors.lastname: Price
authors.affiliation: AIDS Vaccine Design and Development Laboratory, International AIDS Vaccine Initiative (IAVI), Brooklyn, NY, USA; Molecular and Cellular Biology Program, State University of New York, Brooklyn, NY, USA.
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Parks
mesh_terms: D000328:Adult; D000351:Africa, Eastern; D019943:Amino Acid Substitution; D057134:Antibodies, Neutralizing / Q000097:blood*; D000914:Antibodies, Viral / Q000097:blood*; D003429:Cross Reactions; D004217:Distemper Virus, Canine / Q000276:immunology*; D005260:Female; D064368:Healthy Volunteers; D006388:Hemagglutinins / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008297:Male; D008459:Measles virus / Q000276:immunology*; D008875:Middle Aged; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D017422:Sequence Analysis, DNA; D016036:Seroepidemiologic Studies; D010948:Viral Plaque Assay; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology*; D055815:Young Adult
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D006388:Hemagglutinins; D014764:Viral Proteins
keywords: Canine distemper virus; Cross-neutralization; Hemagglutinin; Measles virus; Neutralizing antibody; Plaque reduction neutralization test; Pre-existing immunity