Apoferritin nanoparticle based dual-antigen influenza conjugate vaccine with potential cross-protective efficacy against heterosubtypic influenza virus (Open Access)--颗粒学报PARTICUOLOGY

Sheng, Y., Wei, J., Li, Z., Su, Z., Ma, G., & Zhang, S. (2022). Apoferritin nanoparticle based dual-antigen influenza conjugate vaccine with potential cross-protective efficacy against heterosubtypic influenza virus. Particuology, 64, 56-64. https://doi.org/10.1016/j.partic.2021.04.001

Apoferritin nanoparticle based dual-antigen influenza conjugate vaccine with potential cross-protective efficacy against heterosubtypic influenza virus (Open Access)

Yanan Sheng ^{a b 1}, Jiangxue Wei ^{a b 1}, Zhengjun Li ^a, Zhiguo Su ^a, Guanghui Ma ^a, Songping Zhang ^a *

a State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China
b University of Chinese Academy of Sciences, Beijing 100049, China

10.1016/j.partic.2021.04.001

Volume 64, May 2022, Pages 56-64

Received 15 March 2021, Revised 14 April 2021, Accepted 14 April 2021, Available online 28 April 2021, Version of Record 17 December 2021.

E-mail: spzhang@ipe.ac.cn

Highlights

• M2e or/and HA antigen from H1N1 influenza virus was chemically conjugated to Aft.

• AFt-(PEG)₂₄-HA can confer higher protective efficacy than AFt-(PEG)₂₄-M2e antigen.

• AFt-(PEG)₂₄-M2e/HA dual-antigen vaccine elicits M2e and HA specific antibodies.

• The dual-antigen vaccine provides complete protection against homologous H1N1 virus.

• The vaccine shows potential cross-protective effect against heterosubtypic virus.

Abstract

Ferritin nanoparticles with self-assembling properties have been widely explored as vaccine carrier by displaying foreign antigens through genetic fusion strategy. In the present work, an apoferritin (AFt) nanoparticle was tested as influenza vaccine carrier by chemically conjugating a matrix protein 2 ectodomain (M2e) antigen peptide or/and the full-length hemagglutinin (HA) antigen on the outer surface of the AFt, with heterobifunctional sSMCC or SM(PEG)₂₄ containing PEG chain as linkers. To each AFt nanoparticle, about 30–32 M2e or 1.8 HA antigen could be coupled. The AFt-(PEG)₂₄-M2e, in which the M2e was coupled through SM(PEG)₂₄ containing PEG chain, conferred higher protective efficacy in immunized mice than AFt-M2e did, but was less effective than AFt-(PEG)₂₄-HA. When both M2e and HA were coupled, the synthesized dual-antigen vaccine candidate AFt-(PEG)₂₄-M2e/HA elicited high level of M2e and HA antigen-specific antibodies and conferred 100% protection against lethal infection of homologous PR8 H1N1 virus strain and 70% protection against a heterologous A/FM/1/47 (FM1, H1N1) strain, which was more effective than the M2e or HA single antigen vaccine candidates. The potential cross-protective effect of the dual-antigen vaccine was further demonstrated by significant specific hemagglutination inhibition (HAI) titers in serum of the immunized mice against three other heterologous viral strains including A/Singapore/GP1908/2015 (IVR-180) H1N1, A/Anhui/1/2005 H5N1, and A/Hong Kong H3N2.

Graphical abstract

Keywords

Influenza vaccine; Apoferritin nanoparticle; Hemagglutinin; M2e; Conjugate vaccine

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