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Early neutralizing IgG response to Chikungunya virus in infected patients targets a dominant linear epitope on the E2 glycoprotein.

Kam YW, Lum FM, Teo TH, Lee WW, Simarmata D, Harjanto S, Chua CL, Chan YF, Wee JK, Chow A, Lin RT, Leo YS, Le Grand R, Sam IC, Tong JC, Roques P, Wiesmüller KH, Rénia L, Rötzschke O, Ng LF - EMBO Mol Med (2012)

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.

View Article: PubMed Central - PubMed

Affiliation: Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore.

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Related in: MedlinePlus

IgG from CHIKV-infected NHP plasma recognize E2EP3 and neutralize CHIKV infection in-vitroE2EP3 specific antibodies titers in plasma samples (0, 9 and 13 days pi) were determined by E2EP3 specific peptide-based ELISA at a dilution of 1:2000. Data are presented as mean ± SD.Anti-E2EP3 antibodies in CHIKV-infected NHP plasma were specifically blocked by soluble E2EP3 peptide, and followed by in vitro neutralization assay as described in Materials and Methods. Results are expressed as percentage infection relative to 0 dpi. Data are presented as mean ± SD. A set of serial dilutions from 1:100 to 1:3200 was made and samples assayed were performed in triplicates. *p < 0.05; **p < 0.01; ***p < 0.001 by two-way ANOVA with Bonferroni's multiple comparisons test.
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fig07: IgG from CHIKV-infected NHP plasma recognize E2EP3 and neutralize CHIKV infection in-vitroE2EP3 specific antibodies titers in plasma samples (0, 9 and 13 days pi) were determined by E2EP3 specific peptide-based ELISA at a dilution of 1:2000. Data are presented as mean ± SD.Anti-E2EP3 antibodies in CHIKV-infected NHP plasma were specifically blocked by soluble E2EP3 peptide, and followed by in vitro neutralization assay as described in Materials and Methods. Results are expressed as percentage infection relative to 0 dpi. Data are presented as mean ± SD. A set of serial dilutions from 1:100 to 1:3200 was made and samples assayed were performed in triplicates. *p < 0.05; **p < 0.01; ***p < 0.001 by two-way ANOVA with Bonferroni's multiple comparisons test.

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.


Early neutralizing IgG response to Chikungunya virus in infected patients targets a dominant linear epitope on the E2 glycoprotein.

Kam YW, Lum FM, Teo TH, Lee WW, Simarmata D, Harjanto S, Chua CL, Chan YF, Wee JK, Chow A, Lin RT, Leo YS, Le Grand R, Sam IC, Tong JC, Roques P, Wiesmüller KH, Rénia L, Rötzschke O, Ng LF - EMBO Mol Med (2012)

IgG from CHIKV-infected NHP plasma recognize E2EP3 and neutralize CHIKV infection in-vitroE2EP3 specific antibodies titers in plasma samples (0, 9 and 13 days pi) were determined by E2EP3 specific peptide-based ELISA at a dilution of 1:2000. Data are presented as mean ± SD.Anti-E2EP3 antibodies in CHIKV-infected NHP plasma were specifically blocked by soluble E2EP3 peptide, and followed by in vitro neutralization assay as described in Materials and Methods. Results are expressed as percentage infection relative to 0 dpi. Data are presented as mean ± SD. A set of serial dilutions from 1:100 to 1:3200 was made and samples assayed were performed in triplicates. *p < 0.05; **p < 0.01; ***p < 0.001 by two-way ANOVA with Bonferroni's multiple comparisons test.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3376860&req=5

fig07: IgG from CHIKV-infected NHP plasma recognize E2EP3 and neutralize CHIKV infection in-vitroE2EP3 specific antibodies titers in plasma samples (0, 9 and 13 days pi) were determined by E2EP3 specific peptide-based ELISA at a dilution of 1:2000. Data are presented as mean ± SD.Anti-E2EP3 antibodies in CHIKV-infected NHP plasma were specifically blocked by soluble E2EP3 peptide, and followed by in vitro neutralization assay as described in Materials and Methods. Results are expressed as percentage infection relative to 0 dpi. Data are presented as mean ± SD. A set of serial dilutions from 1:100 to 1:3200 was made and samples assayed were performed in triplicates. *p < 0.05; **p < 0.01; ***p < 0.001 by two-way ANOVA with Bonferroni's multiple comparisons test.
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.

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.

View Article: PubMed Central - PubMed

Affiliation: Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore.

Show MeSH
Related in: MedlinePlus