Chikungunya virus E2 B domain nanoparticle immunogen elicits homotypic neutralizing antibody in mice

Tong K, Hernandez EM, Basore K, Fremont DH, Lai JR. Chikungunya virus E2 B domain nanoparticle immunogen elicits homotypic neutralizing antibody in mice. Vaccine. 2024 Dec 2;42(26):126405. doi: 10.1016/j.vaccine.2024.126405. Epub 2024 Oct 15. PMID: 39413488; PMCID: PMC11645211. Abstract: Alphaviruses are enveloped, positive-sense single-stranded RNA viruses that cause severe human and animal illness. Arthritogenic alphaviruses, such as Chikungunya virus (CHIKV) and Mayaro virus (MAYV), are globally distributed, transmitted by mosquitoes, and can cause rheumatic disease characterized by fever, rash, myalgia, and peripheral polyarthralgia that can persist for years post-infection. These infections can also result in more severe clinical manifestations such as hemorrhage, encephalopathy, and mortality. Several potent monoclonal antibodies (mAbs) with broad neutralizing activity have been shown to bind to the E2 B domain (E2-B) of the alphavirus glycoprotein, suggesting that E2-B epitopes are a site of susceptibility for multiple arthritogenic alphaviruses. However, it is unknown whether E2-B alone can elicit a broadly neutralizing humoral response. Here, we generate and characterize nanoparticle-based immunogens containing CHIKV and MAYV E2-B. Immunization with the CHIKV E2-B nanoparticle elicited sera that were cross-reactive toward CHIKV and MAYV E2-B, but had only homotypic neutralizing activity (serum titer of 1:512) against CHIKV vaccine strain 181/25. Furthermore, immunization with MAYV E2-B nanoparticles elicited non-neutralizing antibody, but sera were cross-reactive for both CHIKV and MAYV E2-B. Our findings suggest that the immunodominant epitopes within CHIKV and MAYV E2-B are bound by cross-reactive, but not cross-neutralizing antibody. Therefore, development of broad E2-B based vaccines that induce broadly neutralizing antibody responses will require engineering to alter the immunodominant landscape. Dataset description: This dataset contains three PRISM files containing raw data tables and corresponding figures used to generate the ELISA and virus neutralization assays reported in the manuscript. B domain Paper_B domain ELISA figures.pzfx This PRISM project file contains ELISA data measuring the reactivity of monoclonal antibodies against the N-terminal regions of CHIKV and MAYV B domains, both in free recombinant and nanoparticle-conjugated forms, with log concentration values. These correspond to Figures 1E and 2G in the publication. B domain Paper_IC50 graphs_corrected dilution.prism This PRISM file contains neutralization assay data, measured as -logIC50, from mice immunized with either 1. lumiazine synthase (LS); 2. LS-CHIKV-B nanoparticles; or 3. LS-MAYV-B nanoparticles. These data correspond to Figure 3 in the publication. B domain paper_serum ELISA figures compiled.pzfx This PRISM project file contains plate readings for all ELISA assays conducted for the analysis, including antibody titers for mice at 57 days post-immunization.