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An Apoferritin–Hemagglutinin Conjugate Vaccine with Encapsulated Nucleoprotein Antigen Peptide from Influenza Virus Confers Enhanced Cross Protection
journal contribution
posted on 2020-07-28, 16:22 authored by Jiangxue Wei, Zhengjun Li, Yanli Yang, Guanghui Ma, Zhiguo Su, Songping ZhangNaturally 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 hemagglutinin (HA) protein on the outer surface of
the AFt. Benefiting from the excellent thermal stability and thermallyassociated
structural flexibility of the AFt nanocages, a novel temperature shift
based encapsulation process was proposed and proved efficient for
encapsulation of the NP peptides. On average, about 18 NPs were encapsulated
and 1.6 HA antigens were conjugated in each of the HA-AFt+NP dual-antigen
influenza vaccines. 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 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 was further demonstrated by 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 the HA-AFt conjugate vaccine. This biomimetic HA-AFt+NP conjugate
vaccine, therefore, may represent a new strategy for developing a
potential universal influenza vaccine without the need of any adjuvant,
and further broaden the application of AFt nanocages in the areas
of vaccine development and delivery system.