Early neutralizing IgG response to Chikungunya virus in infected patients targets a dominant linear epitope on the E2 glycoprotein.
Bottom Line: E2EP3 is located at the N-terminus of the E2 glycoprotein and prominently exposed on the viral envelope.Screening of E2EP3 across different patient cohorts and in non-human primates demonstrated the value of this epitope as a good serology detection marker for CHIKV infection already at an early stage.Mice vaccinated by E2EP3 peptides were protected against CHIKV with reduced viremia and joint inflammation, providing a pre-clinical basis for the design of effective vaccine against arthralgia-inducing CHIKV and other alphaviruses.
Affiliation: Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore.Show MeSH
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Mentions: Non-human primates (NHP) are the most relevant and commonly used pre-clinical models for viruses (Higgs & Ziegler, 2010; Labadie et al, 2010; Liu et al, 2007; Morgan et al, 2008). To explore whether the E2EP3 epitope is also a main target for the protective response, plasma samples from CHIKV-infected NHP were characterized with regards to their reactivity against E2EP3. Nine days after CHIKV-infection, plasma samples had already detectable anti-CHIKV IgG titers and importantly, also detected E2EP3 specifically (Fig 7A and Supporting information Fig 2B). In in vitro neutralization assays CHIKV-infected NHPs plasma reduced CHIKV infectivity by 80% (Fig 7B). Addition of soluble E2EP3 peptide abrogated the inhibitory effect of monkey plasma samples significantly throughout the whole dilution series (from 1:100 to 1:3200) when compared to the untreated plasma samples (Fig 7B). Thus, as in humans, E2EP3 antibodies are part of the protective CHIKV response in NHPs.
Affiliation: Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore.