Wei J, Li Z, Yang Y, Ma G, Su Z, Zhang S. An apoferritin-haemagglutinin conjugate vaccine with encapsulated nucleoprotein antigen peptide from influenza virus confers enhanced cross protection. Bioconjug Chem. 2020;10.1021/acs.bioconjchem.0c00
Naturally occurring self-assembling ferritin nanoparticles have become widely appreciated for vaccine design. In this study, an apoferritin (AFt) nanocage was used as a carrier to construct a biomimetic influenza vaccine by encapsulating a conserved internal nucleoprotein (NP) antigen peptide inside the nanocage, followed by chemically conjugating the surface antigen haemagglutinin (HA) protein on outer surface of the AFt. Benefited from the excellent thermal stability and thermal-associated structural flexibility of the AFt nanocages, a novel temperature-shift based encapsulation process was proposed and proved efficient for encapsulation of the NP peptides. Averagely, about 18 NP were encapsulated and 1.6 HA antigens were conjugated in each of the HA.AFt+NP dual-antigen influenza vaccine. Upon immunization in mice, the HA.AFt+NP vaccine elicited both HA and NP-specific antibodies, and conferred complete protection against a lethal infection of both homologous PR8 H1N1 and a heterologous A/FM/1/47 (FM1, H1N1) strains, while the HA.AFt conjugate vaccine without encapsulated NP antigen only conferred 60% protection against the FM1 H1N1 viral challenge. The potential cross-protective effect of the HA.AFt+NP vaccine were further demonstrated by a significant specific hemagglutination inhibition (HAI) titers in serum of the immunized mice against heterologous A/Hong Kong/4801/2014 (H3N2) viral strain, which was about 3-fold of that induced by HA antigen and 2-fold of HA.AFt conjugate. This biomimetic HA.AFt+NP conjugate vaccine, therefore, may represent a new strategy for developing a potential universal influenza vaccine without need of any adjuvant, and further broaden the application of AFt nanocages in the areas of vaccine development and delivery system.
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