ICMR-National Institute of Virology, 20-A, Dr. Ambedkar Road, Pune 411001, India.
Bioinformatics Centre, Savitribai Phule Pune University, Pune 411007, India.
Viruses. 2023 Nov 10;15(11):2243. doi: 10.3390/v15112243.
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.
在 2012-2016 年期间报告的疑似麻疹病例中，研究了疫苗和野生型麻疹病毒（MeV）的中和抗体（Nt-Ab）反应。在经实验室确认或未通过 IgM 抗体存在确认的血清（Panel A；n = 68（麻疹免疫）和 Panel B；n = 50（未接种疫苗））中研究了针对 MeV A、D4 和 D8 基因型的中和活性。此外，在 Panel A 中还针对 MeV 疫苗和四种野生型病毒测量了 Nt-Ab 反应。使用 MeV-血凝素（H）和融合（F）蛋白的同源建模和分子动力学模拟（MDS）比较了中和结果。总体而言，与 MeV-D4 和 MeV-D8 病毒相比，MeV-A 的 Nt-Ab 滴度发现明显较低。在 MeV-D8 病毒（Jamnagar 和 New Delhi）之间，Nt-Ab 滴度之间没有明显差异，而在 MeV-D4 病毒（Sindhudurg 和 Bagalkot（BGK）病毒）之间，Nt-Ab 滴度之间存在显著差异。有趣的是，在 H-蛋白的表位中观察到的取代被观察到是 MeV-BGK 所特有的。H-蛋白的 MDS 显示由于 L249P 取代而导致中和表位的显著波动。大多数临床疑似病例均显示对 MeV 野生型的 Nt-Abs。与 IgM-阳性病例相比，IgM-阴性病例的 IgG 抗体亲和力和 Nt-Ab 滴度更高，表明再次感染或突破。MDS 显示由于 H-表位的构象灵活性降低而导致中和作用降低。
