Recent advances in “universal” influenza virus antibodies: the rise of a hidden trimeric interface in hemagglutinin globular head

Abstract

Influenza causes seasonal outbreaks yearly and unpredictable pandemics with high morbidity and mortality rates. Despite significant efforts to address influenza, it remains a major threat to human public health. This issue is partially due to the lack of antiviral drugs with potent antiviral activity and broad reactivity against all influenza virus strains and the rapid emergence of drug-resistant variants. Moreover, designing a universal influenza vaccine that is sufficiently immunogenic to induce universal antibodies is difficult. Some novel epitopes hidden in the hemagglutinin (HA) trimeric interface have been discovered recently, and a number of antibodies targeting these epitopes have been found to be capable of neutralizing a broad range of influenza isolates. These findings may have important implications for the development of universal influenza vaccines and antiviral drugs. In this review, we focused on the antibodies targeting these newly discovered epitopes in the HA domain of the influenza virus to promote the development of universal anti-influenza antibodies or vaccines and extend the discovery to other viruses with similar conformational changes in envelope proteins.

Keywords

influenza virus / neutralizing antibody / hemagglutinin / globular head region / trimeric interface

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (Nos. 81822027 and 81630090), the National Key R&D Program of China (No. 2019YFA0904400), the National Science and Technology Major Projects of Infectious Disease funds (No. 2018ZX10301403), and the grant from the Chinese Academy of Medical Sciences (No. 2019PT350002).

Compliance with ethics guidelines

Yulu Wang, Dan Hu, Yanling Wu, and Tianlei Ying declare that they have no conflict of interest. This manuscript is a review article and does not involve a research protocol requiring approval by the relevant institutional review board or ethics committee.

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