Recombinant envelope protein-1 (E1) and E2 of Chikungunya virus (CHIKV) has been shown to elicit neutralizing antibodies and a balanced Th1/Th2 response in mice however with limited protection. Recently reported CHIK virus-like particles showed augmented immunity and protection in adult mice in comparison to E1 and E2, however exacerbated the disease in aged subjects. In order to improve the overall efficacy of protein based vaccines, novel strategies need to be adopted. The discovery of IgM Fc receptor (FcμR) and its role in humoral immune response led us to hypothesise that fusion of an antigen with Fc of IgM may enhance its immunogenicity by polymerizing it and FcμR mediated activation of B and other immune cells. We report in the current study, expression of E2 subunit of CHIKV in fusion with various IgM Fc domains/peptides in E. coli, their in-vitro refolding, characterization and immune response in C57BL/6 mice. Candidates fused with CH3-CH4 Fc fragment produced stable oligomers, whereas the one fused with peptides remained monomeric. The latter elicited a strong humoral and a balanced Th1/Th2 response in mice, whereas the polymeric candidate despite eliciting a strong humoral response, stimulated a biased Th1 response and exhibited higher virus neutralization in Vero cells.

基孔肯雅病毒（CHIKV）的重组包膜蛋白1（E1）和E2已显示在小鼠中引起中和抗体和平衡的Th1 / Th2反应，但保护作用有限。最近报道的CHIK病毒样颗粒与E1和E2相比，在成年小鼠中显示出增强的免疫力和保护作用，但加剧了老年受试者的疾病。为了提高基于蛋白质的疫苗的整体功效，需要采用新的策略。IgM Fc受体（FcμR）的发现及其在体液免疫反应中的作用使我们提出一个假设，即抗原与IgM Fc的融合可能通过使其聚合以及FcμR介导的B和其他免疫细胞的活化而增强其免疫原性。我们在目前的研究中报告，CHIKV的E2亚基与各种IgM Fc域/肽融合的表达大肠杆菌，它们在C57BL / 6小鼠中的体外重折叠，表征和免疫反应。与CH3-CH4 Fc片段融合的候选蛋白可产生稳定的寡聚物，而与肽融合的候选物仍为单体。后者在小鼠中引起强烈的体液和平衡的Th1 / Th2反应，而聚合候选物尽管引起强烈的体液反应，却刺激了有偏向的Th1反应并在Vero细胞中表现出更高的病毒中和作用。