Flu Universal Vaccines: New Tricks on an Old Virus
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REVIEW
Flu Universal Vaccines: New Tricks on an Old Virus Ruikun Du1,2,3
•
Qinghua Cui1,2,3 • Lijun Rong4
Received: 6 June 2020 / Accepted: 5 August 2020 Ó Wuhan Institute of Virology, CAS 2020
Abstract Conventional influenza vaccines are based on predicting the circulating viruses year by year, conferring limited effectiveness since the antigenicity of vaccine strains does not always match the circulating viruses. This necessitates development of universal influenza vaccines that provide broader and lasting protection against pan-influenza viruses. The discovery of the highly conserved immunogens (epitopes) of influenza viruses provides attractive targets for universal vaccine design. Here we review the current understanding with broadly protective immunogens (epitopes) and discuss several important considerations to achieve the goal of universal influenza vaccines. Keywords Influenza virus Universal vaccine Conserved epitopes Broadly protection
Introduction More than 100 years past the catastrophic 1918 Spanish influenza pandemic, influenza viruses remain a constant global health threat. Three types of influenza viruses infect humans: type A (influenza A virus, IAV), type B (IBV) and type C (ICV). Two IAV subtypes (H3N2 and H1N1pdm09) and two IBV lineages (Yamagata and Victoria) co-circulate annually, causing seasonal epidemics and up to 650,000 respiratory deaths globally, while ICV is detected less frequently and usually causes mild infections (Krammer et al. 2018; WHO 2018). In addition, antigenically novel IAVs generated by reassortment of the segmented genome can occasionally infect humans with high rates of & Lijun Rong [email protected] & Ruikun Du [email protected] 1
College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China
2
Qingdao Academy of Chinese Medicinal Sciences, Shandong University of Traditional Chinese Medicine, Qingdao 266122, China
3
Experimental Center, Shandong University of Traditional Chinese Medicine, Jinan 250355, China
4
Department of Microbiology and Immunology, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA
morbidity and mortality, as well as potential pandemic risk (Krammer et al. 2018; WHO 2018). Vaccines provide cost-effective protection against influenza. Currently, seasonal influenza virus vaccines predominantly induce antibody responses against the hemagglutinin (HA), one of the two major surface glycoproteins of the virus (Krammer 2019). However, the majority of vaccine-induced antibodies are directed against the highly plastic head region of HA and are strain-specific (Caton et al. 1982; Heaton et al. 2013). Amino acid residues on the surface of this immunodominant head region vary substantially among different strains and change continuously (referred to as antigenic drift), leading to new circulating virus strains (Wang and Palese 2011). Therefore, current influenza vaccines have to be reformulated each year b
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