Penton base induces better protective immune responses than fiber and hexon as a subunit vaccine candidate against adenoviruses

Human adenoviruses (AdVs) have been extensively studied as vectors for gene therapy and vaccination. However, little attention has been paid to AdV vaccine development and treatment. Currently, there is a lack of information concerning the immunogenicity of AdV major capsid proteins. Here, using AdV7 as a model, we compared the immunogenicity and protection efficacy of its three major capsid proteins in DNA forms, pFiber, pHexon and pPenton, on a mouse model. Quantification of antigen-specific antibodies showed that pHexon induced highest IgG in sera while pPenton induced highest IgA in respiratory mucosae. A neutralization assay revealed that pPenton elicited the highest neutralizing activity against the homologous AdV7 in both sera and bronchoalveolar lavages (BALs). In addition, sera and BALs from mice immunized with either of the three constructs had cross-neutralizing activities against the heterologous AdV3. Furthermore, pHexon and pPenton induced Th1/2- and Th1/17-biased cellular responses, respectively, with pFiber being the weakest in the induction of cellular responses. Virus challenge assay showed that, pPenton group had the fastest virus clearance rate, followed by pFiber and pHexon groups. Likewise, the inflammation in the lung was well controlled in pPenton group against virus challenge. Taken together, our data demonstrate that penton base is better than fiber and hexon as a vaccine candidate against AdVs. Our findings provide important information for the development of subunit vaccines against AdVs.