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Research Article

A bivalent live-attenuated vaccine candidate elicits protective immunity against human adenovirus types 4 and 7

, , , , , , & show all
Pages 1947-1959 | Received 29 Jun 2021, Accepted 12 Sep 2021, Published online: 27 Sep 2021
 

ABSTRACT

Human adenovirus types 4 (HAdV4) and 7 (HAdV7) often lead to severe respiratory diseases and occur epidemically in children, adults, immune deficiency patients, and other groups, leading to mild or severe symptoms and even death. However, no licensed adenovirus vaccine has been approved in the market for general use. E3 genes of adenovirus are generally considered nonessential for virulence and replication; however, a few studies have demonstrated that the products of these genes are also functional. In this study, most of the E3 genes were deleted, and two E3-deleted recombinant adenoviruses (ΔE3-rAdVs) were constructed as components of the vaccine. After E3 deletion, the replication efficiencies and cytopathogenicity of ΔE3-rAdVs were reduced, indicating that ΔE3-rAdVs were attenuated after E3 genes deletion. Furthermore, single immunization with live-attenuated bivalent vaccine candidate protects mice against challenge with wild-type human adenovirus types 4 and 7, respectively. Vaccinated mice demonstrated remarkably decreased viral loads in the lungs and less lung pathology compared to the control animals. Taken together, our study confirms the possibility of the two live-attenuated viruses as a vaccine for clinic use and illustrates a novel strategy for the construction of an adenovirus vaccine.

Acknowledgements

We thank professor Zhong Huang at Institut Pasteur of Shanghai provided anti-HAdV4 monoclonal antibody.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was chiefly supported by funds from National Natural Science Foundation of China [grant numbers 32070926, 31870922], and the key project of Tianjin Natural Science Foundation [grant number 20JCZDJC00090] to DZ, and partially supported by Natural Science Foundation for Universities of Jiangsu Province [grant number 18KJB180018] to CZ.