Recombinant Adenoviruses Displaying Matrix 2 Ectodomain Epitopes on Their Fiber Proteins as Universal Influenza Vaccines.
Influenza is a zoonotic disease that poses severe threats to public health and the global economy. Reemerging influenza pandemics highlight the demand for universal influenza vaccines. We developed a novel virus platform using extracellular domain IV of the matrix 2 protein (M2e), AdC68-F3M2e, by introducing three conserved M2e epitopes into the HI loop of the chimpanzee adenovirus (AdV) fiber protein. The M2e epitopes were expressed sufficiently on the AdV virion surface without affecting fiber trimerization. Additionally, one recombinant adenovirus, AdC68-F3M2e(H1-H5-H7), induced robust M2e-specific antibody responses in BALB/c mice after two sequential vaccinations and conferred efficient protection against homologous and heterologous influenza virus (IV) challenges. We found that the use of AdV with tandem M2e epitopes in fiber is a potential strategy for influenza prevention.IMPORTANCE Influenza epidemics and pandemics severely threaten public health. Universal influenza vaccines have increasingly attracted interest in recent years. Here, we describe a new strategy that incorporates triple M2e epitopes into the fiber protein of chimpanzee adenovirus 68. We optimized the process of inserting foreign genes into the AdC68 structural protein by one-step isothermal assembly and demonstrated that this 225-bp HI loop insertion could be well tolerated. Furthermore, two doses of adjuvant-free fiber-modified AdC68 could confer sufficient protection against homologous and heterologous influenza virus infections in mice. Our results show that AdC68-F3M2e could be pursued as a novel universal influenza vaccine.
['Tang|Xinying|X|', 'Yang|Yong|Y|', 'Xia|Xiaoli|X|', 'Zhang|Chao|C|', 'Yang|Xi|X|', 'Song|Yufeng|Y|', 'Dai|Xinyi|X|', 'Wang|Min|M|', 'Zhou|Dongming|D|']
D000256:Adenoviridae D000818:Animals D002642:Chick Embryo D003429:Cross Reactions D000939:Epitopes D005260:Female D057809:HEK293 Cells D006801:Humans D053118:Influenza A Virus, H1N1 Subtype D053127:Influenza A Virus, H9N2 Subtype D007252:Influenza Vaccines D007251:Influenza, Human D008807:Mice, Inbred BALB C D014611:Vaccination D014614:Vaccines, Synthetic D014763:Viral Matrix Proteins
universal influenza vaccine M2e HI loop adenovirus immune responses