title: Impact of systemic or mucosal immunity to adenovirus on Ad-based Ebola virus vaccine efficacy in guinea pigs.
abstract: BACKGROUND
  Approximately 35% of the North American population and an estimated 90% of the sub-Saharan African population have antibodies against adenovirus serotype 5 (AdHu5) that are capable of neutralizing AdHu5-based vaccines. In mice, intranasal delivery of AdHu5 expressing the Zaire ebolavirus glycoprotein human adenovirus serotype 5 (Ad) containing the genes for the Zaire ebolavirus glycoprotein (ZGP) under the expressional control of a cytomegalovirus immediate early promoter (CMV)) can bypass systemic preexisting immunity, resulting in protection against mouse-adapted Zaire ebolavirus (Mayinga 1976).
  
  
  METHODS
  Guinea pigs administered an adenovirus-based Ebola virus vaccine either intramuscularly or intranasally in the presence of systemically or mucosally induced adenovirus immunity were challenged with a lethal dose of guinea pig-adapted Zaire ebolavirus (Mayinga 1976) (GA-ZEBOV). The humoral immune response was assayed to determine the effect of vaccine delivery route and preexisting immunity.
  
  
  RESULTS
  Intramuscular or intranasal vaccination fully protected guinea pigs against a lethal GA-ZEBOV challenge. However, intramuscular vaccination in animals with systemically induced preexisting immunity resulted in low survival following challenge. Interestingly, intranasal vaccination protected guinea pigs with systemic preexisting immunity to AdHu5. Mucosal adenoviral immunity induced by intranasal administration of AdHu5 decreased protection following intranasal vaccination with the first-generation but not with the second-generation vaccine.
  
  
  CONCLUSIONS
  Intranasal vaccination is an effective vaccine delivery route in the presence of systemic and, to a lower extent, mucosal preexisting immunity to the vaccine vector in guinea pigs.
authors: Special Pathogens Department, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Canada.
authors: Jason S
authors: JS
authors: Richardson
authors: Max C
authors: MC
authors: Abou
authors: Kaylie N
authors: KN
authors: Tran
authors: Anand
authors: A
authors: Kumar
authors: Beni M
authors: BM
authors: Sahai
authors: Gary P
authors: GP
authors: Kobinger
mesh_terms: D000256:Adenoviridae / Q000276:immunology*; D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis* / Q000097:blood; D001402:B-Lymphocytes / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D046129:Ebola Vaccines / Q000008:administration & dosage* / Q000276:immunology / Q000592:standards*; D006023:Glycoproteins / Q000378:metabolism; D006168:Guinea Pigs; D019142:Hemorrhagic Fever, Ebola / Q000517:prevention & control*; D006801:Humans; D007273:Injections, Intramuscular; D009297:Nasal Mucosa / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology / Q000592:standards
chemical_list: D000914:Antibodies, Viral; D046129:Ebola Vaccines; D006023:Glycoproteins; D014614:Vaccines, Synthetic