title: A porcine adenovirus with low human seroprevalence is a promising alternative vaccine vector to human adenovirus 5 in an H5N1 virus disease model.
abstract: Human adenovirus 5 (AdHu5) vectors are robust vaccine platforms however the presence of naturally-acquired neutralizing antibodies may reduce vector efficacy and potential for re-administration. This study evaluates immune responses and protection following vaccination with a replication-incompetent porcine adenovirus 3 (PAV3) vector as an alternative vaccine to AdHu5 using an avian influenza H5N1 disease model. Vaccine efficacy was evaluated in BALB/c mice following vaccination with different doses of the PAV3 vector expressing an optimized A/Hanoi/30408/2005 H5N1 hemagglutinin antigen (PAV3-HA) and compared with an AdHu5-HA control. PAV3-HA rapidly generated antibody responses, with significant neutralizing antibody titers on day 21, and stronger cellular immune responses detected on day 8, compared to AdHu5-HA. The PAV3-HA vaccine, administered 8 days before challenge, demonstrated improved survival and lower virus load. Evaluation of long-term vaccine efficacy at 12 months post-vaccination showed better protection with the PAV3-HA than with the AdHu5-HA vaccine. Importantly, as opposed to AdHu5, PAV3 vector was not significantly neutralized by human antibodies pooled from over 10,000 individuals. Overall, PAV3-based vector is capable of mediating swift, strong immune responses and offer a promising alternative to AdHu5.
authors.affiliation: National Microbiology Laboratory, Public Health Agency of Canada, Canadian Science Centre for Human and Animal Health, Winnipeg, Canada.
authors.forename: Ami
authors.initials: A
authors.lastname: Patel
authors.forename: Suresh
authors.initials: S
authors.lastname: Tikoo
authors.forename: Gary
authors.initials: G
authors.lastname: Kobinger
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D025662:Adenoviruses, Porcine / Q000235:genetics* / Q000276:immunology; D000818:Animals; D004285:Dogs; D005822:Genetic Vectors; D006801:Humans; D056724:Immunity, Humoral; D007074:Immunoglobulin G / Q000737:chemistry; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids / Q000378:metabolism; D016036:Seroepidemiologic Studies; D016896:Treatment Outcome; D014777:Virus Diseases
chemical_list: D007074:Immunoglobulin G