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.

Evolution and Interspecies Transmission of Canine Distemper Virus—An Outlook of the Diverse Evolutionary Landscapes of a Multi-Host Virus

“…Therefore, it is possible to hypothesize that immunity against MeV may have protected humans against CDV infection or at least avoided the presentation of clinical signs [116]. In non-human primate models infected with CDV and vaccinated against MeV, the antibodies generated in these animals partially cross-react against CDV protecting them from the clinical disease [102,125]. The possibility that MeV vaccination stops in the future in several geographical regions due to the success of the eradication program, allows us to think that the CDV can possibly jump the species barrier, infect humans and cause clinical disease in humans similar to that already reported in non-human primates [106,115,125].…”

Efficient generation of vesicular stomatitis virus (VSV)-pseudotypes bearing morbilliviral glycoproteins and their use in quantifying virus neutralising antibodies

“…These data suggest that the humoral responses of UK dogs to vaccination against CDV differ in their epitope specificities; some dogs recognising determinants that are broadly conserved between CDV and PPRV while other dogs mount a largely CDV-specific response. Recent studies have noted that a proportion of human sera contain weak cross-neutralising antibodies against CDV [54] , suggesting that a potent anti-measles response may induce a low level cross-neutralising response to CDV. Our data would suggest that the potency of the heterologous neutralising response is not solely dependent on the homologous antibody titre; rather there are qualitative differences in the breadth of the neutralising response to infection between hosts.…”

Probing Morbillivirus Antisera Neutralization Using Functional Chimerism between Measles Virus and Canine Distemper Virus Envelope Glycoproteins

“…Site-directed mutagenesis (QuikChange Site-Directed Mutagenesis Kit; Agilent Technologies, Santa Clara, CA, United States) was used to remove a SpeI site in CDV-H and to introduce a Y537D substitution, shown to diminish neutralization activity in human serum [7]. All constructs were C-terminally fused to 6 × His and subcloned into pCG-H plasmid via PacI/SpeI sites [40].…”

“…This characteristic poses a more than theoretical risk that CDV could extend into the human population after MeV eradication [4,5,6]. Even though high titers of MeV-neutralizing antibodies have been shown to protect against CDV infection [7], those levels are not routinely achieved through vaccination [4].…”