title: Efficacy of severe acute respiratory syndrome vaccine based on a nonhuman primate adenovirus in the presence of immunity against human adenovirus.
abstract: Replication-deficient human adenovirus type 5 (AdH5) vectors can induce strong transgene product-specific cellular and humoral responses. However, many adult humans have neutralizing antibodies (NAbs) against AdH5 as a result of natural infection with this virus. Therefore, a chimpanzee adenovirus C7 (AdC7) vector was developed to circumvent interference by preexisting immunity to AdH5. This study evaluated the impact of preexisting immunity to human adenovirus on the efficacy of adenovirus-based vaccines against the coronavirus that causes severe acute respiratory syndrome (SARS-CoV). Efficacy was assessed after intramuscular injection of the vector into mice and was measured as the frequency of SARS-CoV-specific T cells and NAbs against SARS-CoV. Immunogenicity of the AdH5-based vaccine was significantly attenuated or completely abolished when the preexisting anti-AdH5 NAb titer was higher than 40. Because 27% of human serum samples from the United States tested so far have an anti-AdH5 NAb titer higher than 40, our results suggested that a significant percentage of humans with preexisting anti-AdH5 immunity would not be candidates for vaccination with an AdH5-based genetic vaccine. In contrast, preexisting anti-AdH5 NAbs have a minimal effect on the potency of the AdC7-based genetic vaccine. Taken together, our studies warrant the further development of AdC7 as a vaccine carrier for human trials.
authors.affiliation: Gene Therapy Program, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, 19104, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhi
authors.forename: Joanita
authors.initials: J
authors.lastname: Figueredo
authors.forename: Gary P
authors.initials: GP
authors.lastname: Kobinger
authors.forename: Heather
authors.initials: H
authors.lastname: Hagan
authors.forename: Roberto
authors.initials: R
authors.lastname: Calcedo
authors.forename: James R
authors.initials: JR
authors.lastname: Miller
authors.forename: Guangping
authors.initials: G
authors.lastname: Gao
authors.forename: James M
authors.initials: JM
authors.lastname: Wilson
mesh_terms: D000260:Adenoviruses, Human / Q000276:immunology*; D000261:Adenoviruses, Simian / Q000276:immunology*; D000328:Adult; D000818:Animals; D000910:Antibodies, Heterophile / Q000096:biosynthesis; D000914:Antibodies, Viral / Q000096:biosynthesis* / Q000097:blood; D000918:Antibody Specificity; D005822:Genetic Vectors; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D002679:Pan troglodytes / Q000821:virology; D045473:Severe acute respiratory syndrome-related coronavirus / Q000276:immunology*; D045169:Severe Acute Respiratory Syndrome / Q000276:immunology / Q000517:prevention & control; D013601:T-Lymphocytes / Q000276:immunology; D022721:Vaccines, Virosome / Q000276:immunology
chemical_list: D000910:Antibodies, Heterophile; D000914:Antibodies, Viral; D022721:Vaccines, Virosome