The antigenic landscape of human influenza N2 neuraminidases from 2009 until 2017
0301 basic medicine
Mouse
QH301-705.5
Science
VACCINE
Neuraminidase
neuraminidase
Antibodies, Viral
Mice
Viral Proteins
Orthomyxoviridae Infections
HONG-KONG INFLUENZA
INFECTION
Influenza, Human
Medicine and Health Sciences
Humans
Animals
PROTECTION
Biology (General)
GENETIC EVOLUTION
Antigens, Viral
Microbiology and Infectious Disease
0303 health sciences
Influenza A Virus, H3N2 Subtype
Q
R
Ferrets
Biology and Life Sciences
H3N2
Antigenic Variation
3. Good health
ANTIBODY
Influenza Vaccines
VIRUS
Medicine
Other
influenza
DOI:
10.7554/elife.90782
Publication Date:
2023-10-09T19:29:20Z
AUTHORS (19)
ABSTRACT
Human H3N2 influenza viruses are subject to rapid antigenic evolution which translates into frequent updates of the composition of seasonal influenza vaccines. Despite these updates, the effectiveness of influenza vaccines against H3N2-associated disease is suboptimal. Seasonal influenza vaccines primarily induce hemagglutinin-specific antibody responses. However, antibodies directed against influenza neuraminidase (NA) also contribute to protection. Here, we analysed the antigenic diversity of a panel of N2 NAs derived from human H3N2 viruses that circulated between 2009 and 2017. The antigenic breadth of these NAs was determined based on the NA inhibition (NAI) of a broad panel of ferret and mouse immune sera that were raised by infection and recombinant N2 NA immunisation. This assessment allowed us to distinguish at least four antigenic groups in the N2 NAs derived from human H3N2 viruses that circulated between 2009 and 2017. Computational analysis further revealed that the amino acid residues in N2 NA that have a major impact on susceptibility to NAI by immune sera are in proximity of the catalytic site. Finally, a machine learning method was developed that allowed to accurately predict the impact of mutations that are present in our N2 NA panel on NAI. These findings have important implications for the renewed interest to develop improved influenza vaccines based on the inclusion of a protective NA antigen formulation.
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CITATIONS (5)
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