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Characterization of Rotavirus Strains Responsible for Breakthrough Diarrheal Diseases among Zambian Children Using
Innocent Mwape1,2, Natasha Makabilo Laban1,3, Kennedy Chibesa1,4
1Enteric Disease and Vaccine Research Unit, Centre for Infectious Disease Research in Zambia, Lusaka P.O. Box 34681, Zambia.
Insights
Rotavirus (RV) infections in vaccinated children can occur due to genetically altered strains evading immunity. This study identified reassortant RV strains in Zambia, suggesting a need to update vaccination strategies and develop more effective universal RV vaccines.
Area of Science:
- Virology
- Immunology
- Public Health
Background:
- Rotavirus (RV) infection remains a significant cause of diarrheal disease globally, particularly in high-burden settings.
- Breakthrough RV infections in vaccinated children highlight the challenge of vaccine efficacy against evolving viral strains.
- Limited characterization of RV strains causing breakthrough infections in resource-limited countries hinders effective disease control.
Purpose of the Study:
- To characterize the genetic makeup of rotavirus strains detected in fully vaccinated children in Zambia.
- To investigate potential immune evasion mechanisms of these breakthrough RV strains.
Main Methods:
- Whole genome sequencing of rotavirus strains from diarrheal stool specimens using Illumina MiSeq.
- Bioinformatic analysis for whole genome assembly and strain characterization.
- Comparison of antigenic epitopes between breakthrough strains and vaccine strains.
Main Results:
- Four out of 76 (5.2%) specimens were positive for rotavirus.
- Identified reassortant strains (RVA/Human-wt/ZMB/CIDRZ-RV2088/2020/G1P[4] and RVA/Human-wt/ZMB/CIDRZ-RV2106/2020/G12P[4]) and a typical Wa-like strain (RVA/Human-wt/ZMB/CIDRZ-RV2150/2020/G12P[8]).
- Observed amino acid differences in VP7 and VP4 antigenic epitopes between breakthrough and Rotarix vaccine strains, suggesting a role in immune evasion.
Conclusions:
- The identified reassortant rotavirus strains possess genetic variations potentially contributing to immune evasion.
- These findings underscore the importance of ongoing surveillance and genetic characterization of rotavirus strains.
- The study provides crucial data to inform national rotavirus vaccination strategies and the development of next-generation universal rotavirus vaccines.
Abstract:
The occurrence of rotavirus (RV) infection among vaccinated children in high-burden settings poses a threat to further disease burden reduction. Genetically altered viruses have the potential to evade both natural infection and vaccine-induced immune responses, leading to diarrheal diseases among vaccinated children. Studies characterizing RV strains responsible for breakthrough infections in resource-limited countries where RV-associated diarrheal diseases are endemic are limited. We aimed to characterize RV strains detected in fully vaccinated children residing in Zambia using next-generation sequencing. We conducted whole genome sequencing on Illumina MiSeq. Whole genome assembly was performed using Geneious Prime 2023.1.2. A total of 76 diarrheal stool specimens were screened for RV, and 4/76 (5.2%) were RV-positive. Whole genome analysis revealed RVA/Human-wt/ZMB/CIDRZ-RV2088/2020/G1P[4]-I2-R2-C2-M2-A2-N2-T2-E2-H2 and RVA/Human-wt/ZMB/CIDRZ-RV2106/2020/G12P[4]-I1-R2-C2-M2-A2-N1-T2-E1-H2 strains were mono and multiple reassortant (exchanged genes in bold) respectively, whilst RVA/Human-wt/ZMB/CIDRZ-RV2150/2020/G12P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1 was a typical Wa-like strain. Comparison of VP7 and VP4 antigenic epitope of breakthrough strains and Rotarix strain revealed several amino acid differences. Variations in amino acids in antigenic epitope suggested they played a role in immune evasion of neutralizing antibodies elicited by vaccination. Findings from this study have the potential to inform national RV vaccination strategies and the design of highly efficacious universal RV vaccines.
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