title: Universal influenza vaccines: Shifting to better vaccines.
abstract: Influenza virus causes acute upper and lower respiratory infections and is the most likely, among known pathogens, to cause a large epidemic in humans. Influenza virus mutates rapidly, enabling it to evade natural and vaccine-induced immunity. Furthermore, influenza viruses can cross from animals to humans, generating novel, potentially pandemic strains. Currently available influenza vaccines induce a strain specific response and may be ineffective against new influenza viruses. The difficulty in predicting circulating strains has frequently resulted in mismatch between the annual vaccine and circulating viruses. Low-resource countries remain mostly unprotected against seasonal influenza and are particularly vulnerable to future pandemics, in part, because investments in vaccine manufacturing and stockpiling are concentrated in high-resource countries. Antibodies that target conserved sites in the hemagglutinin stalk have been isolated from humans and shown to confer protection in animal models, suggesting that broadly protective immunity may be possible. Several innovative influenza vaccine candidates are currently in preclinical or early clinical development. New technologies include adjuvants, synthetic peptides, virus-like particles (VLPs), DNA vectors, messenger RNA, viral vectors, and attenuated or inactivated influenza viruses. Other approaches target the conserved exposed epitope of the surface exposed membrane matrix protein M2e. Well-conserved influenza proteins, such as nucleoprotein and matrix protein, are mainly targeted for developing strong cross-protective T cell responses. With multiple vaccine candidates moving along the testing and development pipeline, the field is steadily moving toward a product that is more potent, durable, and broadly protective than previously licensed vaccines.
authors.affiliation: PATH, 2201 Westlake Avenue Suite 200, Seattle, WA 98121, USA. Electronic address: fberlanda-scorza@path.org.
authors.forename: Francesco
authors.initials: F
authors.lastname: Berlanda Scorza
authors.affiliation: PATH, 2201 Westlake Avenue Suite 200, Seattle, WA 98121, USA.
authors.forename: Vadim
authors.initials: V
authors.lastname: Tsvetnitsky
authors.affiliation: PATH, 2201 Westlake Avenue Suite 200, Seattle, WA 98121, USA.
authors.forename: John J
authors.initials: JJ
authors.lastname: Donnelly
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D035843:Biomedical Research / Q000639:trends; D002986:Clinical Trials as Topic; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology; D006801:Humans; D007252:Influenza Vaccines / Q000627:therapeutic use*; D007251:Influenza, Human / Q000517:prevention & control*; D009975:Orthomyxoviridae; D009976:Orthomyxoviridae Infections / Q000517:prevention & control; D019444:Vaccines, DNA / Q000627:therapeutic use; D014614:Vaccines, Synthetic / Q000627:therapeutic use
chemical_list: D000276:Adjuvants, Immunologic; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic
keywords: Chimeric hemagglutinin; Heterosubtypic immunity; Influenza vaccines; Universal vaccines