Abstract
Influenza viruses remain a constant burden in humans, causing millions of infections and hundreds of thousands of deaths each year. Current influenza virus vaccine modalities primarily induce antibodies directed towards the highly variable head domain of the hemagglutinin protein on the virus surface. Such antibodies are often strain-specific, meaning limited cross-protection against divergent influenza viruses is induced, resulting in poor vaccine efficacy. To attempt to counteract this, yearly influenza vaccination with updated formulations containing antigens from more recently circulating viruses is required. This is an expensive and time-consuming exercise, and the constant arms race between host immunity and virus evolution presents an ongoing challenge for effective vaccine development. Furthermore, there exists the constant pandemic threat of highly pathogenic avian influenza viruses with high fatality rates (~30–50%) or the emergence of new, pathogenic reassortants. Current vaccines would likely offer little to no protection from such viruses in the event of an epidemic or pandemic. This highlights the urgent need for improved influenza virus vaccines capable of providing long-lasting, robust protection from both seasonal influenza virus infections as well as potential pandemic threats. In this narrative review, we examine the next generation of influenza virus vaccines for human use and the steps being taken to achieve universal protection.
Highlights
Influenza viruses are Orthomyxovirus species belonging to the Orthomyxoviridae family [1]
Combining a rAd-based vaccine expressing NP and M2 from a H1N1 virus with a DNA vaccine prime appears to result in increased cross-protection, as illustrated by the protection afforded against H1N1 and H5N1 viruses after vaccination of mice and ferrets [67]
This study showed that the treatment was safe and well tolerated and produced a slight reduction in virus replication, demonstrating the effectiveness of anti-matrix 2 protein ectodomain (M2e) antibodies and validating M2e as a target in an influenza vaccine candidate
Summary
Influenza viruses are Orthomyxovirus species belonging to the Orthomyxoviridae family [1]. Influenza viruses infect the respiratory tract, with symptoms including high fever, dry cough, headache, malaise, rhinorrhea and myalgia, with death as the outcome in severe cases [6]. Influenza viruses cause up to 650,000 deaths globally each year, with 5–20% of the human population contracting non-lethal infections annually [7]. Almost all human influenza infections are caused by H1- and H3-containing strains (H1N1 and H3N2), with two lineages of influenza B virus— Victoria and Yamagata— circulating globally on a seasonal basis [7]. Seasonal infections as well as potential pandemic viruses should be available. If such an ambitious goal were to be achieved, new approaches to influenza virus vaccine development are required. This narrative review focuses on the generation of influenza virus vaccines in the race towards universal protection
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