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: The potential of E2EP3 epitope as a vaccine target was further assessed in a mouse model (Gardner et al, 2010). For this, C57BL/6 mice were vaccinated with E2EP3 covalently linked to KLH in the presence of Freund's Adjuvant. Mice were primed and boosted twice with the immunogen (emulsified first with Complete [CFA] and then with Incomplete Freund's Adjuvant [IFA]) over a period of 21 days. Significant anti-E2EP3 titer was detected 19 days post-vaccination after the 1st boost (Supporting information Figs 2C and 5A) and was further increased after the 2nd boost at 27 days post-vaccination (Supporting information Fig 5B). Importantly, the sera obtained at 27 days post-vaccination were able to neutralize CHIKV-infection in vitro. Compared to the PBS-vaccinated control group, infectivity was reduced by approximately 40% (Fig 8A). Moreover, virus challenge in mice at 30 days post-vaccination indicated a partial protection by E2EP3 as viremia was reduced from 4500 to 2000 pfu/ml at 2 days post-challenge (Fig 8B). This reduction of virus titer was also reflected in clinical symptoms used to monitor the virus-induced inflammation (Supporting information Fig 5C). Maximal footpad swelling in the PBS-vaccinated group was more than twice as that of the E2EP3-vaccinated group (Fig 8C). E2EP3 may therefore be used both as a marker as well as a potential vaccine component in pre-clinical models for CHIKV therapy.
Affiliation: Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore.