Human adenovirus penton dodecahedron nanoparticles induce an enhanced neutralizing antibody response in mouse model

Abstract

Vaccination is the most effective way to prevent infectious diseases and control outbreaks, and nanoparticles are highly suitable platforms for protein-based vaccines. Human adenovirus type 7 (Ad7) is one of the main pathogens causing severe pneumonia. A safe and effective vaccine against Ad7 infection is urgently needed. Penton-dodecahedron (Pt-Dd) nanoparticles, can be generated by the spontaneous assembly of the penton during the replication cycle of human adenovirus type 3. Adenovirus type 3 Pt-Dd has been studied as drug delivery vehicles. However, little attention has been paid to whether Pt-Dd can elicit a neutralizing antibody response, serve as an adenovirus vaccine candidate. In this study, we designed a Pt-Dd nanoparticle vaccine by co-expressing the penton base and fiber of Ad7 with the insect cell-baculovirus expression system and evaluated its immunogenicity in mice. The results showed that Ad7 Pt-Dd induced high titers of neutralizing antibody production and triggered a strong cellular immune response. In contrast, Ad7 penton base nanoparticles induced low levels of neutralizing antibody responses and strong cellular immune responses. Ad7 Pt-Dd immunization provided immune protection against Ad7 pneumonia in humanized desmoglein-2 receptor transgenic mice. In summary, Ad7 Pt-Dd nanoparticles induce protective humoral and cellular immune responses and can be used as a vaccine candidate against Ad7 infection. This study enhances our comprehension of human adenovirus neutralizing antigens and broadens the spectrum of applications for adenovirus Pt-Dd nanoparticles.