The
neutralizing antibody (Nt-Ab) response to
vaccine and wild-type
measles viruses (MeV) was studied in suspected
measles cases reported during the years 2012-2016. The neutralization activity against
MeV A, D4 and D8 genotypes was studied on sera (Panel A; n = 68 (
measles-immunized) and Panel B; n = 50 (unvaccinated)) that were either laboratory confirmed or not confirmed by the presence of
IgM antibodies. Additionally, the Nt-Ab response in Panel A was measured against the MeV
vaccine and four wild-type viruses. Neutralization results were compared using homology modeling and molecular dynamics simulation (MDS) of MeV-
hemagglutinin (H) and fusion (F)
proteins. Overall, the Nt-Ab titres for
MeV-A were found to be significantly lower than MeV-D4 and MeV-D8 viruses for Panel A. No major difference was noted in Nt-Ab titres between MeV-D8 viruses (Jamnagar and New Delhi), whereas MeV-D4 (Sindhudurg and Bagalkot (BGK) viruses) showed significant differences between Nt-Ab titres for Panel B. Interestingly, the substitutions observed in
epitopes of H-
protein, L249P and G316A are observed to be unique to MeV-BGK. MDS of H-
protein revealed significant fluctuations in neutralizing
epitopes due to L249P substitution. The majority of the clinically suspected cases showed Nt-Abs to MeV wild-types. Higher
IgG antibody avidity and Nt-Ab titres were noted in
IgM-negatives than in
IgM-positives cases, indicating
reinfection or breakthrough. MDS revealed reduced neutralization due to decreased conformational flexibility in the H-
epitope.