Abstract
BackgroundInfluenza viruses evolve rapidly and undergo immune driven selection, especially in the hemagglutinin (HA) protein. We report amino acid changes affecting antigenic epitopes and receptor‐binding sites of A(H3N2) viruses circulating in Kilifi, Kenya, from 2009 to 2017.MethodsNext‐generation sequencing (NGS) was used to generate A(H3N2) virus genomic data from influenza‐positive specimens collected from hospital admissions and health facility outpatients presenting with acute respiratory illness to health facilities within the Kilifi Health and Demographic Surveillance System. Full‐length HA sequences were utilized to characterize A(H3N2) virus genetic and antigenic changes.ResultsFrom 186 (90 inpatient and 96 outpatient) influenza A virus‐positive specimens processed, 101 A(H3N2) virus whole genomes were obtained. Among viruses identified in inpatient specimens from 2009 to 2015, divergence of circulating A(H3N2) viruses from the vaccine strains A/Perth/16/2009, A/Texas/50/2012, and A/Switzerland/9715293/2013 formed 6 genetic clades (A/Victoria/208/2009‐like, 3B, 3C, 3C.2a, 4, and 7). Among viruses identified in outpatient specimens from 2015 to 2017, divergence of circulating A(H3N2) viruses from vaccine strain A/Hong Kong/4801/2014 formed clade 3C.2a, subclades 3C.2a2 and 3C.2a3, and subgroup 3C.2a1b. Several amino acid substitutions were associated with the continued genetic evolution of A(H3N2) strains in circulation.ConclusionsOur results suggest continuing evolution of currently circulating A(H3N2) viruses in Kilifi, coastal Kenya and suggest the need for continuous genetic and antigenic viral surveillance of circulating seasonal influenza viruses with broad geographic representation to facilitate prompt and efficient selection of influenza strains for inclusion in future influenza vaccines.
Highlights
Seasonal influenza viruses infect 5%-15% of the global population annually, resulting in 290 000-650 000 deaths each year.[1,2] The disease burden is highest in developing countries especially in sub-Saharan Africa,[3,4,5] where influenza viruses may circulate year-round without clear seasonality; this is in contrast to the clear seasonality observed in temperate climatic regions.[6]
As vaccine effectiveness may not be fully explained by antigenic analysis using the hemagglutinin inhibition (HI) assay, the availability of high-throughput platforms to characterize HA genetic groups, for example, next-generation sequencing (NGS) techniques, can provide more timely information to evaluate protection afforded by vaccination
Among the virus strains identified in the outpatient specimens, the A(H3N2) viruses belonged to genetic clade 3C.2A(34/66), subclades 3C.2a2 (3/66) and 3C.2a3 (6/66), and subgroup 3C.2a1b (23/66) all of which significantly diverged from the 2016-17 vaccine strain A/Hong Kong/4801/2014 (H3N2)-like virus (Figure 3)
Summary
Seasonal influenza viruses infect 5%-15% of the global population annually, resulting in 290 000-650 000 deaths each year.[1,2] The disease burden is highest in developing countries especially in sub-Saharan Africa,[3,4,5] where influenza viruses may circulate year-round without clear seasonality; this is in contrast to the clear seasonality observed in temperate climatic regions.[6]. The HA glycoprotein is the primary target of host neutralizing antibodies, which inhibit the binding of HA to sialic acid receptors present on epithelial cell membranes of the upper respiratory tract.[12] Influenza A(H3N2) virus HA possesses defined antigenic epitopes (five sites designated A through E) and receptor-binding sites.[13] Accumulation of mutations at these antigenic sites results in viral escape from the host immune response.[14,15] These sequence drifts on the HA from accumulated mutations are observed more frequently in A(H3N2) virus than A(H1N1) virus.[8,16] For example, during the 2013-14 influenza season, A(H3N2) virus clade 3C.2a viruses possessing a new glycosylation site in antigenic site B of HA emerged and predominated among circulating A(H3N2) viruses which led to a low or null vaccine effectiveness for that season.[17,18,19,20] As vaccine effectiveness may not be fully explained by antigenic analysis using the hemagglutinin inhibition (HI) assay, the availability of high-throughput platforms to characterize HA genetic groups, for example, next-generation sequencing (NGS) techniques, can provide more timely information to evaluate protection afforded by vaccination. We characterized the genetic changes in A(H3N2) viruses circulating in coastal Kenya using full-length HA sequences generated through next-generation sequencing (NGS) from respiratory specimens collected from inpatient and outpatient sentinel surveillance sites in coastal Kenya from 2009 to 2017
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
