Abstract
Adenovirus vaccine vectors generated from new viral serotypes are routinely screened in pre-clinical laboratory animal models to identify the most immunogenic and efficacious candidates for further evaluation in clinical human and veterinary settings. Here, we show that studies in a laboratory species do not necessarily predict the hierarchy of vector performance in other mammals. In mice, after intramuscular immunization, HAdV-5 (Human adenovirus C) based vectors elicited cellular and humoral adaptive responses of higher magnitudes compared to the chimpanzee adenovirus vectors ChAdOx1 and AdC68 from species Human adenovirus E. After HAdV-5 vaccination, transgene specific IFN-γ+ CD8+ T cell responses reached peak magnitude later than after ChAdOx1 and AdC68 vaccination, and exhibited a slower contraction to a memory phenotype. In cattle, cellular and humoral immune responses were at least equivalent, if not higher, in magnitude after ChAdOx1 vaccination compared to HAdV-5. Though we have not tested protective efficacy in a disease model, these findings have important implications for the selection of candidate vectors for further evaluation. We propose that vaccines based on ChAdOx1 or other Human adenovirus E serotypes could be at least as immunogenic as current licensed bovine vaccines based on HAdV-5.
Highlights
Replication-defective recombinant adenoviruses are widely employed as vectors in the development of both human and veterinary vaccines [14,16,40]
The ability of AdC68 and ChAdOx1 to induce transgene product specific T cell and antibody responses was compared with HAdV5 in a series of dose-response experiments in mice with vectors encoding the model antigen TIPeGFP [1]
This study revealed marked differences in the relative magnitude of transgene product specific T cell and antibody responses elicited by human and chimpanzee adenovirus vectors in two mammalian species
Summary
Replication-defective recombinant adenoviruses are widely employed as vectors in the development of both human and veterinary vaccines [14,16,40]. Pre-existing neutralising antibodies to common human adenoviruses such as human adenovirus serotype 5 (HAdV-5) may have contributed to the lack of clinical efficacy of some vaccine vectors based on this serotype in human trials [21]. Adenoviruses isolated from chimpanzees and other great apes group phylogenetically within the human adenovirus species [32] but the seroprevalence of neutralising antibodies against these serotypes in humans is considerably lower than against HAdV-5, prompting the development of chimpanzee adenoviruses (ChAds) as vaccine vectors [8,42]. A new foot-and-mouth disease virus (FMDV) vaccine based on this serotype has recently been licensed in the United States for use in cattle [27]. Some studies have successfully used serotypes originating from the target species, such as bovine adenovirus vectors in cattle, despite pre-existing immunity to the vector [46]. The use of alternative adenovirus serotypes has yet to be fully explored
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
