Induction of Influenza (H5N8) Antibodies by Modified Vaccinia Virus Ankara H5N1 Vaccine

To the Editor: Aquatic birds form a natural reservoir of avian influenza viruses from which new human and animal influenza viruses originate. After initial detection in 2010 in China, a new highly pathogenic avian influenza (HPAI) virus of the H5N8 subtype reemerged in ducks in South Korea in 2014 (1,2). The hemagglutinin gene of this virus was distantly related to those of H5N1 subtypes that have caused infections in humans since 1997 (3). The World Health Organization/World Organisation for Animal Health/Food and Agriculture Organization of the United Nations H5N1 Evolution Working Group has assigned this new H5 to clade 2.3.4.4. Several poultry farms in the Netherlands, Germany, United Kingdom, and Italy were recently affected by infection with H5N8 virus closely related to the strains circulating in Asia (4), leading to implementation of preventive measures to restrict viral spread. Human infections with this new HPAI subtype have not been reported. Modified vaccinia virus Ankara (MVA) is a promising viral vector platform for the development of influenza vaccines (5). We previously conducted a randomized doubleblind phase 1/2a trial in young healthy persons to evaluate an MVA-based H5 vaccine (registered in the Netherlands’ trial register under NTR3401). Preclinical testing was conducted before this trial (6,7). Thirty-nine study participants received MVA-H5-serumfree Munich-Rotterdam (sfMR), which encoded hemagglutinin of influenza virus A/Vietnam/1194/2004 (H5N1), and 40 received vector control. Persons received 1 or 2 doses (with an interval of 4 weeks) of 107 or 108 PFU. Twenty-seven of the MVA-H5-sfMR– vaccinated persons received a booster vaccination 1 year later (again 107 or 108 PFU). The MVA-based vaccine was well tolerated and induced antibodies to both the homologous (A/Vietnam/1194/2004, clade 1) and a heterologous (A/Indonesia/5/2005, clade 2.1) H5N1 virus (8). Although the newly emerged HPAI (H5N8) virus thus far has been detected only in birds, zoonotic transmission to humans exposed to large numbers of infected birds might occur (e.g., during culling operations). Therefore, shortly after the H5N8 outbreak in poultry in the Netherlands, we determined whether MVA-H5-sfMR–induced antibodies cross-react with the new H5N8 strain. Post-infection A/Vietnam/1194/2004 (clade 1) ferret serum (infected with a low pathogenic reverse genetics virus produced with hemagglutinin and