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Title: Canine distemper virus neutralization activity is low in human serum and it is sensitive to an amino acid substitution in the hemagglutinin protein

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. - Highlights: • Screened 146 serum samples for measles virus (MV) and canine distemper virus (CDV) neutralizing antibody (nAb). • MV nAb is prevalent in the sera. • CDV neutralizing activity is generally low or absent and when detected it is present in sera with high MV nAb titers. • Amore » neutralization-resistant CDV mutant was isolated using human serum selection. • A mutation was identified in the receptor-binding region of CDV hemagglutinin protein that confers the neutralization resistance.« less
Authors:
 [1] ;  [2] ; ; ; ;  [1] ;  [3] ;  [4] ;  [5] ;  [6] ;  [7] ;  [8] ;  [9] ;  [8] ;  [2] ;  [1] ;  [2]
  1. AIDS Vaccine Design and Development Laboratory, International AIDS Vaccine Initiative (IAVI), Brooklyn, NY (United States)
  2. (United States)
  3. Kenya AIDS Vaccine Initiative (KAVI)-Institute of Clinical Research, Nairobi (Kenya)
  4. Centre for Geographic Medicine Research, Kenya Medical Research Institute (KEMRI), Kilifi, Kenya & Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Headington (United Kingdom)
  5. MRC/UVRI Uganda Virus Research Unit on AIDS, Masaka and Entebbe (Uganda)
  6. Projet San Francisco, Kigali (Rwanda)
  7. Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA (United States)
  8. Department of Medical Affairs, International AIDS Vaccine Initiative, NY, NY (United States)
  9. Human Immunology Laboratory, International AIDS Vaccine Initiative, London (United Kingdom)
Publication Date:
OSTI Identifier:
22470182
Resource Type:
Journal Article
Resource Relation:
Journal Name: Virology; Journal Volume: 482; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ADULTS; AFRICA; AMINO ACIDS; ANTIBODIES; DOGS; DOSES; GLYCOPROTEINS; HUMAN POPULATIONS; IMMUNITY; MEASLES VIRUS; MUTANTS; MUTATIONS; RECEPTORS