Evolution and Vaccine Efficacy Analysis of Haemagglutinin 1 (HA1) Domain of Influenza A Viruses that Circulated in Kenya Between the 2007 and 2013 Seasons

Abstract

The influenza virus is one of the most infectious and contagious pathogens in the world. The pathogens evolve rapidly causing regular seasonal epidemics in humans and other mammalian species and also posing a challenge to effective vaccination. The study sought to evaluate the evolutionary dynamics of the human influenza A viruses that circulated in Kenya just before, during, and after the 2009 pandemic. A/H3N2, A/sH1N1, and A/H1N1pdm09 HA1 nucleotide sequences, previously deposited in GenBank and GISAID genetic databases were retrieved including those of corresponding WHO influenza virus vaccine strain compositions. A total of A/H3N2 (N=122); A/sH1N1 (N=126) and A/H1N1pdm09 (N=176) Kenyan and global reference sequences virus isolates the three datasets were analysed using bioinformatics approaches. The Kenyan A/H3N2 viruses revealed mutations across the antigenic sites (A-E) whereas the A/sH1N1displayed mutations at the antigenic site Cb and Ca2 and Sb. However, the mutations revealed by A/H1N1pdm09 did not occur at any designated antigenic site. Phylogenetic analysis showed that the A/H3N2- viruses clustered with A/Brisbane 10/2007 like, with a drift to A/Perth/16/2009 (H3N2)-like viruses in 2013. The majority of A/H1N1pdm09 (2009-2011) belonged to clade 7 while a minority of clade 5 and 6A and the Kenyan A/sH1N1 belonged to clade B. Vis-à-vis N-linked glycosylation all the isolates in the three categories retained all the potential N-linked glycosylation sites. The Kenyan A/H3N2 evolved mainly through purifying selection while the A/H1N1pdm09, and A/sH1N1 evolved under negative selection. The Kenyan A/H3N2, A/H1N1pdm09 & A/sH1N1 isolates shared tMRCA at 7.5 (95% HPD = 6.4-8.9), 5.9 (95% HPD = 4.7-7.1) and 2.7 (95% HPD = 2.3-3.2) years ago, respectively. The A/H3N2 revealed modest vaccine efficaciousness during 2008, and 2010 influenza seasons, whilst sub-optimal effectiveness was registered in 2007, 2009, 2012, and 2013. The A/H1N1pdm09 estimates indicate 80% effectiveness for the years 2009-2011 and the worst case for the subsequent year (below 40%,). Likewise, A/sH1N1 efficaciousness was modest in the 2008 season, declining in the following season (below45%). The mean evolutionary rate of the Kenyan A/H3N2, A/H1N1pdm09 and A/sH1N1 isolates was 4.6x10-3 (95% HPD = 3.0x10-3 to 6.3x10-3), 5.4x10-3 (95% HPD = 4.0x10-3 to 7.2x10-3) and 5.1x10-3 (95% HPD = 3.3x10-3 to 7.0x10-3) nucleotide substitutions per site per year, respectively.In conclusion, constant evolution and viral amino acid changes at the HA1 domain play a vital role in vaccine efficaciousness shaping the evolutionary dynamics of local influenza A viruses. Our findings underscore the importance and need for consistent surveillance and molecular characterization of influenza viruses, to inform decision-making and enhance early detection of strains with epidemic/pandemic potential as well as benefit in guiding decisions regarding the appropriate annual influenza vaccine formulation