Comparative immunogenicity of bacterially expressed soluble trimers and nanoparticle displayed influenza hemagglutinin stem immunogens

• DOI: 10.1101/2021.03.14.435294
• Publication Date: 2021-03-15T22:25:42Z
• Authors: Uddipan Kar; Sara Khaleeq; Priyanka Garg; Madhuraj Bhat; Poorvi Reddy; Venkada Subramani...; Aditya Upadhyaya; Mili Das; Ghadiyaram Chaksh...; Suman Pandey; Somnath Dutta; Raghavan Varadarajan
• Keywords: Immunogen; Trimer; Heterologous

Abstract Current influenza vaccines need to be updated annually due mutations in the globular head of viral surface protein, hemagglutinin (HA). To address this, vaccine candidates have been designed based on relatively conserved HA stem domain and shown protective efficacy animal models. Oligomerization antigens either by fusion oligomerization motifs or display self-assembling nanoparticle scaffolds, can induce more potent immune responses compared corresponding monomeric antigen multivalent engagement B-cells. Since increase manufacturing complexity, often involves one mammalian cell expressed components, it is important characterize compare various scaffolds. Using a structure guided approach, we successfully displayed multiple copies previously soluble, trimeric immunogen, pH1HA10, ferritin like MsDps2 (12 copies), Ferritin (24 copies) Encapsulin (180 copies). All proteins were Escherichia coli . The immunogens found well folded bound directed broadly neutralizing antibodies with high affinity. An 8.5 Å Cryo-EM map Msdps2-pH1HA10 confirmed successful design immunogen. Mice immunization studies soluble constructs revealed that all them immunogenic, protected mice against homologous (A/Belgium/145-MA/2009) heterologous (A/Puerto Rico/8/1934) challenge 10MLD 50 mouse adapted virus. Although conferred small but statistically significant improvement protection relative trimer challenge, was similar both nanoparticle-stem immunized groups. Such rapidly producible, bacterially scaffolds are useful modalities tackle future pandemics.