The Impact of Genetic Variation on Duck Hepatitis A Virus (DHAV) Vaccine Efficacy: A Comparative Study of DHAV-1 and DHAV-3 Against Emerging Variant Strains

<b>Background/Objective:</b> Duck virus hepatitis (DVH), caused by duck hepatitis A virus (DHAV), poses significant challenges to duck farming due to high mortality rates in young ducklings. Despite the widespread use of live attenuated vaccines, the genetic diversity within DHAV strains has diminished their cross-protection efficacy. This study aimed to evaluate the cross-protective efficacy of current DHAV-1 and DHAV-3 vaccines against genetically divergent wild strains. <b>Methods:</b> Phylogenetic analyses of the VP1 genes from DHAV-1 and DHAV-3 were conducted. Both DHAV-1 and DHAV-3 vaccines were tested in ducklings, with and without maternal-derived antibodies (MDA), through challenge trials with homologous and heterologous strains. <b>Results:</b> In the phylogenetic analysis, compared to vaccine strains, DHAV-1 and DHAV-3 field variant strains were classified into different genotypes. In ducklings without MDA, the DHAV-1 vaccine provided 60% survival against homologous strains by 2 days post-vaccination (DPV) and complete protection by 4 DPV, while survival rates against heterologous strains ranged from 40 to 60%. In ducklings with MDA, the DHAV-1 vaccine provided full protection with an additional vaccination for day-old ducklings against heterologous strains. The DHAV-3 vaccine conferred complete protection against both homologous and heterologous strains by 2 DPV, regardless of MDA presence. <b>Conclusions:</b> The DHAV-3 vaccine demonstrated robust cross-protection across genotypes, while the DHAV-1 vaccine showed limitations against genetically divergent strains. These findings highlight the necessity for genotype-matched vaccines and optimized immunization strategies to enhance protection against evolving DHAV field strains.