Increased substitution rate in H5N1 avian influenza viruses during mass vaccination of poultry

As a means of heated debate,mass vaccination of poultry has been used in some countries to control H5N1 highly pathogenic avian influenza(HPAI),which remains of global economic and public health significance.Theoretically,mass vaccination can act as an evolutionary selective force facilitating the emergence of vaccine-resistant viruses,similar to that widespread use of antibiotics facilitates the emergence of antibiotic-resistant bacteria.To support the hypothesis,the substitution rates in the two subunits,HA1 and HA2,of the viral hemagglutinin gene,were calculated using a Bayesian Markov Chain Monte Carlo(MCMC) approach.It was found that the rate in the HA1 subunit,but not in the HA2 subunit,increased significantly during periods of mass vaccination(2005 2010 in China and 2003 2009 in Indonesia),in contrast to the periods when no mass vaccination programs took place(1996 2004 in China and 2004 2008 in Thailand).Because substitutions in the HA1 subunit rather than in the HA2 subunit can lead to vaccine-resistant viruses,the results support that mass vaccination programs facilitate the emergence of vaccine-resistant viruses,which,in turn,will render mass vaccination programs less effective.Therefore,caution must be taken when adopting mass vaccination as a long-term strategy to control HPAI.