Content area
Full Text
Introduction
Replication-defective recombinant adenoviruses are now 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] . ChAd vectors have primed unprecedented frequencies of antigen-specific CD8+ T cells in recent human clinical vaccine trials [26,35,36] .
For veterinary applications, HAdV-5 is still the most commonly used human adenovirus serotype. Indeed, 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] . However, the use of alternative adenovirus serotypes has yet to be fully explored.
Vector serotypes for both human and veterinary applications are currently screened and selected largely on the basis of pre-clinical studies in mice [8] . However, it remains unclear to what extent these pre-clinical studies predict immunogenicity and efficacy in other mammalian species. In this study we compared antigen-specific immune responses elicited by vaccination with a HAdV-5 vector (Human adenovirus C, here referred to as species C) or a new chimpanzee adenovirus vector ChAdOx1 [13] (Human adenovirus E, here referred to as species E), in mice and cattle. In cattle, we tested vectors encoding mycobacterial antigen 85A to represent bovine tuberculosis vaccine candidates in the target species [12,43] . This is the first time, to our knowledge, that a chimpanzee adenovirus vector, or any vector derived from species E, has been tested in a ruminant species. In both species, we demonstrate differences in the ability of vectors of different serotypes to elicit cellular and humoral immune responses. Furthermore, by comparing studies in laboratory animals and cattle, we demonstrate that comparative immunogenicity studies in mice do...