Adenoviruses as vectors for delivering vaccines to mucosal surfaces

Abstract

Immunization of mucosal surfaces has become an attractive route of vaccine delivery because of its ability to induce mucosal immunity. Although various methods of inducing mucosal immunity are being developed, our laboratory has focused on developing adenoviruses as replication-competent and replication-incompetent vectors. The present report will summarize our progress in sequencing the entire bovine adenovirus-3 genome and identifying regions which can be deleted and subsequently used as insertion sites for foreign genes in developing recombinant viral vaccines. Using these recombinant viruses, we demonstrated the 'proof-of-principle' in developing mucosal immunity and, more importantly, inducing protection against bovine herpes virus in a natural host-cattle. Finally, we demonstrated that immunity and protection occurred even in animals that had pre-existing antibodies to the vector.

Fig. 1

Schematic representation of the bovine adenovirus-3 genome (adapted from Reddy et al., 1998). The location of the major regions of the genome are highlighted as are the main viral proteins. The E region codes for early proteins, whereas the L region codes for the late proteins.

Fig. 2

Immunity to BHV-1 gD following immunization with an adenovirus vector expressing gD. Animals were vaccinated either intranasally or intradermally twice at a 4-week interval. A total of 3 weeks after the last immunization, serum antibody and antibody-secreting cells in the lung were assayed by ELISA and ELISPOT, respectively.

Fig. 3

Immune responses to BHV-1 gD following immunization of bovine adenovirus-3 seropositive animals. BAV-3 gD recombinants were administered intranasally on Day 0 and again on Day 28. Serum antibody responses to gD (dark bars) were measured by neutralization and to BAV-3 by ELISA (light-shaded bars).

Fig. 4

Protection of animals from BHV-1 challenge. Animals in Fig. 3 were challenged on Day 40 and assessed for clinical protection.