Influenza Neuraminidase: A Neglected Protein and Its Potential for a Better Influenza Vaccine.

Luca T Giurgea,Matthew J Memoli,Jeffery K Taubenberger,David M Morens

doi:10.3390/vaccines8030409

Luca T Giurgea, Matthew J Memoli + Show 2 more

Open Access

https://doi.org/10.3390/vaccines8030409

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Abstract

Neuraminidase (NA) is an influenza surface protein that helps to free viruses from mucin-associated decoy receptors and to facilitate budding from infected cells. Experiments have demonstrated that anti-NA antibodies protect animals against lethal influenza challenge by numerous strains, while decreasing pulmonary viral titers, symptoms, and lung lesions. Studies in humans during the influenza A/H3N2 pandemic and in healthy volunteers challenged with influenza A/H1N1 showed that anti-NA immunity reduced symptoms, nasopharyngeal viral shedding, and infection rates. Despite the benefits of anti-NA immunity, current vaccines focus on immunity against hemagglutinin and are not standardized to NA content leading to limited and variable NA immunogenicity. Purified NA has been shown to be safe and immunogenic in humans. Supplementing current vaccines with NA may be a simple strategy to improve suboptimal effectiveness. Immunity against NA is likely to be an important component of future universal influenza vaccines.

Highlights

Seasonal influenza vaccination is the best option available to counteract the significant worldwide burden of morbidity and mortality caused by both epidemic and pandemic influenza
While humanity waits for the inevitable influenza pandemic, seasonal influenza continues to be responsible for significant morbidity and mortality across the planet
A rapid mutation rate and the presence of a large reservoir of diverse viruses in animal species have provided influenza with a robust capability to adapt and evade immunity induced by natural infection and vaccination

Summary

Introduction

Seasonal influenza vaccination is the best option available to counteract the significant worldwide burden of morbidity and mortality caused by both epidemic and pandemic influenza. Protective immunity against influenza is considered short lived, and updated yearly vaccination is necessary [2]. Even small changes, such as a single amino-acid mutation, can lead to antigenic drift, causing significant vaccine mismatches due to diminished antibody binding activity [3,4]. All the available data suggest that the addition of NA antigens to current and future vaccine strategies may significantly improve vaccine efficacy, may reduce the impact of novel virus pandemics, and could be an important step forward in the quest for a more broadly protective vaccine. We discuss these data and attempt to identify further areas of research needed that could inform the development of novel vaccines that target the NA of influenza viruses

Neuraminidase and Its Potential as a Vaccine Target

In Vitro and Animal Studies

Importance of NA Immunity in Humans

NA-Based Vaccine Strategies

Findings

Conclusions