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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Main Authors: Sunil R. Vaidya, Neelakshi S. Kumbhar, Gargi K. Andhare, Nilesh Pawar, Atul M. Walimbe, Meenal Kinikar, Sunitha M. Kasibhatla, Urmila Kulkarni-Kale
Format: Article
Language:English
Published: MDPI AG 2023-11-01
Series:Viruses
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Online Access:https://www.mdpi.com/1999-4915/15/11/2243
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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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