Recombinant influenza virus carrying human adenovirus epitopes elicits protective immunity in mice

•A recombinant influenza virus rFLU/HAdV containing HAdV hexon protein epitopes was produced.•rFLU/HAdV induced robust humoral, mucosal, and cell-mediated immune responses against HAdV in vivo.•rFLU/HAdV conferred protection against wild-type HAdV-3 or HAdV-7 challenge.•rFLU/HAdV warrants further investigation as a promising HAdV candidate vaccine.

Human adenoviruses (HAdVs) are known to cause a broad spectrum of diseases in pediatric and adult patients. As this time, there is no specific therapy for HAdV infection. This study used reverse genetics (RG) to successfully rescue a recombinant influenza virus, termed rFLU/HAdV, with the HAdV hexon protein antigenic epitope sequence inserted in the influenza non-structural (NS1) protein gene. rFLU/HAdV morphological characteristics were observed using electron microscopy. Furthermore, BALB/c mice immunized twice intranasally (i.n.) with 104 TCID50 or 105 TCID50 rFLU/HAdV showed robust humoral, mucosal, and cell-mediated immune responses in vivo. More importantly, these specific immune responses could protect against subsequent wild-type HAdV-3 (BJ809) or HAdV-7 (BJ1026) challenge, showing a significant reduction in viral load and a noticeable alleviation of histopathological changes in the challenged mouse lung in a dose-dependent manner. These findings highlighted that recombinant rFLU/HAdV warrants further investigation as a promising HAdV candidate vaccine and underscored that the immuno-protection should be confirmed in primate models.