Neutralizing Antibody Response to Genotypically Diverse Measles Viruses in Clinically Suspected Measles Cases
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...
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2023-11-01
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author | Sunil R. Vaidya Neelakshi S. Kumbhar Gargi K. Andhare Nilesh Pawar Atul M. Walimbe Meenal Kinikar Sunitha M. Kasibhatla Urmila Kulkarni-Kale |
author_facet | Sunil R. Vaidya Neelakshi S. Kumbhar Gargi K. Andhare Nilesh Pawar Atul M. Walimbe Meenal Kinikar Sunitha M. Kasibhatla Urmila Kulkarni-Kale |
author_sort | Sunil R. Vaidya |
collection | DOAJ |
description | 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. |
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spelling | doaj.art-10ac8e9d76334a649bbc7f89b3eb550c2023-11-24T15:10:56ZengMDPI AGViruses1999-49152023-11-011511224310.3390/v15112243Neutralizing Antibody Response to Genotypically Diverse Measles Viruses in Clinically Suspected Measles CasesSunil R. Vaidya0Neelakshi S. Kumbhar1Gargi K. Andhare2Nilesh Pawar3Atul M. Walimbe4Meenal Kinikar5Sunitha M. Kasibhatla6Urmila Kulkarni-Kale7ICMR-National Institute of Virology, 20-A, Dr. Ambedkar Road, Pune 411001, IndiaICMR-National Institute of Virology, 20-A, Dr. Ambedkar Road, Pune 411001, IndiaICMR-National Institute of Virology, 20-A, Dr. Ambedkar Road, Pune 411001, IndiaICMR-National Institute of Virology, 20-A, Dr. Ambedkar Road, Pune 411001, IndiaICMR-National Institute of Virology, 20-A, Dr. Ambedkar Road, Pune 411001, IndiaBioinformatics Centre, Savitribai Phule Pune University, Pune 411007, IndiaBioinformatics Centre, Savitribai Phule Pune University, Pune 411007, IndiaBioinformatics Centre, Savitribai Phule Pune University, Pune 411007, IndiaThe 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.https://www.mdpi.com/1999-4915/15/11/2243Indiameasles virus genotypesneutralization activityserological investigationssuspected measles cases |
spellingShingle | Sunil R. Vaidya Neelakshi S. Kumbhar Gargi K. Andhare Nilesh Pawar Atul M. Walimbe Meenal Kinikar Sunitha M. Kasibhatla Urmila Kulkarni-Kale Neutralizing Antibody Response to Genotypically Diverse Measles Viruses in Clinically Suspected Measles Cases Viruses India measles virus genotypes neutralization activity serological investigations suspected measles cases |
title | Neutralizing Antibody Response to Genotypically Diverse Measles Viruses in Clinically Suspected Measles Cases |
title_full | Neutralizing Antibody Response to Genotypically Diverse Measles Viruses in Clinically Suspected Measles Cases |
title_fullStr | Neutralizing Antibody Response to Genotypically Diverse Measles Viruses in Clinically Suspected Measles Cases |
title_full_unstemmed | Neutralizing Antibody Response to Genotypically Diverse Measles Viruses in Clinically Suspected Measles Cases |
title_short | Neutralizing Antibody Response to Genotypically Diverse Measles Viruses in Clinically Suspected Measles Cases |
title_sort | neutralizing antibody response to genotypically diverse measles viruses in clinically suspected measles cases |
topic | India measles virus genotypes neutralization activity serological investigations suspected measles cases |
url | https://www.mdpi.com/1999-4915/15/11/2243 |
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