Anti-neuraminidase immunity in the combat against influenza

ABSTRACT

Introduction

Anti-neuraminidase (NA) immunity correlates with the protection against influenza virus infection in both human and animal models. The aim of this review is to better understand the mechanism of anti-NA immunity, and also to evaluate the approaches on developing NA-based influenza vaccines or enhancing immune responses against NA for current influenza vaccines.

Areas covered

In this review, the structure of influenza neuraminidase, the contribution of anti-NA immunity to protection, as well as the efforts and challenges of targeting the immune responses to NA were discussed. We also listed some of the newly discovered anti-NA monoclonal antibodies and discussed their contribution in therapeutic as well as the antigen design of a broadly protective NA vaccine.

Expert opinion

Targeting the immune response to both HA and NA may be critical for achieving the optimal protection since there are different mechanisms of HA and NA elicited protective immunity. Monoclonal antibodies (mAbs) that target the conserved protective lateral face or catalytic sites are effective therapeutics. The epitope discovery using monoclonal antibodies may benefit NA-based vaccine elicited broadly reactive antibody responses. Therefore, the potential for a vaccine that elicits cross-reactive antibodies against neuraminidase is a high priority for next-generation influenza vaccines.

KEYWORDS:

• Influenza
• neuraminidase
• hemagglutinin
• vaccine
• antibodies
• anti-NA immunity

Article highlights

• The conserved catalytic site and less antigenicity diversity makes neuraminidase an attractive target for a universal influenza vaccine.

• Both anti-hemagglutinin and anti-neuraminidase immunity contribute to protection, with anti-hemagglutinin immunity clear virus infection, while the anti-neuraminidase immunity is infection permissive.

• Targeting the immune response to both hemagglutinin and neuraminidase may be critical for achieving the optimal protection.

• The low potency and stability of neuraminidase in current influenza vaccines are the main challenges in inducing strong immune responses against neuraminidase.

• Different approaches that aim to enhance anti-neuraminidase immune responses have been tested.

• Isolation and characterization of broadly reactive anti-neuraminidase monoclonal antibodies benefits influenza therapy and discovery of protective epitopes for influenza vaccine development.

Declaration of interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants, patents received or pending, or royalties.

Reviewer disclosures

A reviewer on this manuscript has disclosed that their lab receives funding from Sanofi Pasteur to perform preclinical research on influenza vaccines. Peer reviewers on this manuscript have no other relevant financial or other relationships to disclose.

Author contributions

Conceptualization, X. Zhang and T.M.Ross.; formal analysis, X Zhang and T.M.Ross; investigation, X. Zhang; resources, T.M.Ross; data curation, X Zhang; writing – original draft preparation, X. Zhang; writing – review and editing, X. Zhang and T.M.R.; supervision, T.M.Ross; project administration, X. Zhang; funding acquisition, T.M.Ross. All authors have read and agreed to the published version of the manuscript.

Additional information

Funding

This work has been funded by the University of Georgia and as part of the Collaborative Influenza Vaccine Innovations Centers (CIVICs) by the National Institute of Allergy and Infectious Diseases, a component of the NIH, Department of Health and Human Services, under contract 75N93019C00052. TM Ross is also supported in part as an Eminent Scholar by the Georgia Research Alliance, GRA-001.