ArticlePLoS neglected tropical diseases2015
Identifying the Role of E2 Domains on Alphavirus Neutralization and Protective Immune Responses.
Article in PLoS neglected tropical diseases, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 39 citations in OpenAlex.
- Article
- Rewiring of host cell signaling in chikungunya virus infection: a mechanism for pathogenesis and therapeutic approaches.Archives of microbiology · 2026Review
- In Silico Characterization of Conserved Epitopes in Alphavirus E2 Proteins: A Promising Approach for Pan-vaccine Design.ACS omega · 2025Article
- Deep mutationally scanned CHIKV E3/E2 virus library maps viral amino acid preferences and predicts viral escape mutants of neutralizing CHIKV antibodies.Journal of virology · 2025Article
- Deep mutationally scanned (DMS) CHIKV E3/E2 virus library maps viral amino acid preferences and predicts viral escape mutants of neutralizing CHIKV antibodies.bioRxiv : the preprint server for biology · 2024Article
- Pathogenicity and virulence of chikungunya virus.Virulence · 2024Review
- Enhanced attenuation of chikungunya vaccines expressing antiviral cytokines.NPJ vaccines · 2024Article
- Evolution and immunopathology of chikungunya virus informs therapeutic development.Disease models & mechanisms · 2023Review
- Infection with chikungunya virus confers heterotypic cross-neutralizing antibodies and memory B-cells against other arthritogenic alphaviruses predominantly through the B domain of the E2 glycoprotein.PLoS neglected tropical diseases · 2023Article
- Development of a next-generation chikungunya virus vaccine based on the HydroVax platform.PLoS pathogens · 2022Article
- Two Conserved Phenylalanine Residues in the E1 Fusion Loop of Alphaviruses Are Essential for Viral Infectivity.Journal of virology · 2022Article
- Article
- Chikungunya Virus Vaccines: Platforms, Progress, and Challenges.Current topics in microbiology and immunology · 2022Review
- Article
- Recombinant Baculovirus: A Flexible Drug Screening Platform for Chikungunya Virus.International journal of molecular sciences · 2021Article
- Human mAbs Broadly Protect against Arthritogenic Alphaviruses by Recognizing Conserved Elements of the Mxra8 Receptor-Binding Site.Cell host & microbe · 2020Article
- Arthritogenic Alphavirus Vaccines: Serogrouping Versus Cross-Protection in Mouse Models.Vaccines · 2020Article
- Alphavirus Replication: The Role of Cardiac Glycosides and Ion Concentration in Host Cells.BioMed research international · 2020Review
- Neutralizing antibodies against Mayaro virus require Fc effector functions for protective activity.The Journal of experimental medicine · 2019Article
- Development of a Specific CHIKV-E2 Monoclonal Antibody for Chikungunya Diagnosis.Virologica Sinica · 2019Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
backgroundChikungunya virus (CHIKV) and other alphaviruses are the etiologic agents of numerous diseases in both humans and animals. Despite this, the viral mediators of protective immunity against alphaviruses are poorly understood, highlighted by the lack of a licensed human vaccine for any member of this virus genus. The alphavirus E2, the receptor-binding envelope protein, is considered to be the predominant target of the protective host immune response. Although envelope protein domains have been studied for vaccine and neutralization in flaviviruses, their role in alphaviruses is less characterized. Here, we describe the role of the alphavirus E2 domains in neutralization and protection through the use of chimeric viruses. METHODOLOGY/PRINCIPAL
findingsFour chimeric viruses were constructed in which individual E2 domains of CHIKV were replaced with the corresponding domain from Semliki Forest virus (SFV) (ΔDomA/ΔDomB/ΔDomC/ ΔDomA+B). Vaccination studies in mice (both live and inactivated virus) revealed that domain B was the primary determinant of neutralization. Neutralization studies with CHIKV immune serum from humans were consistent with mouse studies, as ΔDomB was poorly neutralized. CONCLUSIONS/SIGNIFICANCE: Using chimeric viruses, it was determined that the alphavirus E2 domain B was the critical target of neutralizing antibodies in both mice and humans. Therefore, chimeric viruses may have more relevance for vaccine discovery than peptide-based approaches, which only detect linear epitopes. This study provides new insight into the role of alphavirus E2 domains on neutralization determinants and may be useful for the design of novel therapeutic technologies.
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