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.

Keywords: Chimeric hemagglutinin; Heterosubtypic immunity; Influenza vaccines; Universal vaccines.

Fig. 1

Percentage of patient visits for influenza-like illness in the US for selected seasons and years of mismatch. Scale represents percentage of patient visits for influenza-like illness for selected seasons discussed in the text. Data are from the US Centers for Disease Control and Prevention's US Outpatient Influenza-like Illness Surveillance Network. Data for 2014–2015 are through week 10, 2015. (For interpretation of the references to color in the citation of this figure, the reader is referred to the web version of this article.)