title: Optimization of Prime-Boost Vaccination Strategies Against Mouse-Adapted Ebolavirus in a Short-Term Protection Study.
abstract: In nonhuman primates, complete protection against an Ebola virus (EBOV) challenge has previously been achieved after a single injection with several vaccine platforms. However, long-term protection against EBOV after a single immunization has not been demonstrated to this date. Interestingly, prime-boost regimens have demonstrated longer protection against EBOV challenge, compared with single immunizations. Since prime-boost regimens have the potential to achieve long-term protection, determining optimal vector combinations is crucial. However, testing prime-boost efficiency in long-term protection studies is time consuming and resource demanding. Here, we investigated the optimal prime-boost combination, using DNA, porcine-derived adeno-associated virus serotype 6 (AAV-po6), and human adenovirus serotype 5 (Ad5) vector, in a short-term protection study in the mouse model of EBOV infection. In addition, we also investigated which immune parameters were indicative of a strong boost. Each vaccine platform was titrated in mice to identify which dose (single immunization) induced approximately 20% protection after challenge with a mouse-adapted EBOV. These doses were then used to determine the protection efficacy of various prime-boost combinations, using the same mouse model. In addition, humoral and cellular immune responses against EBOV glycoprotein were analyzed by an enzyme-linked immunosorbent assay, a neutralizing antibody assay, and an interferon γ-specific enzyme-linked immunospot assay. When DNA was used as a prime, Ad5 boost induced the best protection, which correlated with a higher cellular response. In contrast, when AAV-po6 or Ad5 were injected first, better protection was achieved after DNA boost, and this correlated with a higher total glycoprotein-specific immunoglobulin G titer. Prime-boost regimens using independent vaccine platforms may provide a useful strategy to induce long-term immune protection against filoviruses.
authors.affiliation: National Microbiology Laboratory, Public Health Agency of Canada University of Manitoba, Winnipeg, Canada.
authors.forename: Jenna
authors.initials: J
authors.lastname: Aviles
authors.affiliation: National Microbiology Laboratory, Public Health Agency of Canada University of Manitoba, Winnipeg, Canada.
authors.forename: Alexander
authors.initials: A
authors.lastname: Bello
authors.affiliation: National Microbiology Laboratory, Public Health Agency of Canada University of Manitoba, Winnipeg, Canada.
authors.forename: Gary
authors.initials: G
authors.lastname: Wong
authors.affiliation: National Microbiology Laboratory, Public Health Agency of Canada University of Manitoba, Winnipeg, Canada.
authors.forename: Hugues
authors.initials: H
authors.lastname: Fausther-Bovendo
authors.affiliation: National Microbiology Laboratory, Public Health Agency of Canada University of Manitoba, Winnipeg, Canada.
authors.forename: Xiangguo
authors.initials: X
authors.lastname: Qiu
authors.affiliation: National Microbiology Laboratory, Public Health Agency of Canada University of Manitoba, Winnipeg, Canada.
authors.forename: Gary
authors.initials: G
authors.lastname: Kobinger
mesh_terms: D000260:Adenoviruses, Human / Q000276:immunology; D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D000229:Dependovirus / Q000276:immunology; D046129:Ebola Vaccines / Q000276:immunology*; D029043:Ebolavirus / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D058501:Enzyme-Linked Immunospot Assay / Q000379:methods; D005822:Genetic Vectors / Q000276:immunology; D006023:Glycoproteins / Q000276:immunology; D019142:Hemorrhagic Fever, Ebola / Q000276:immunology* / Q000821:virology; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D056724:Immunity, Humoral / Q000276:immunology; D007117:Immunization, Secondary / Q000379:methods; D007074:Immunoglobulin G / Q000276:immunology; D051379:Mice; D013552:Swine; D014611:Vaccination / Q000379:methods; D014764:Viral Proteins / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D046129:Ebola Vaccines; D006023:Glycoproteins; D007074:Immunoglobulin G; D014764:Viral Proteins
keywords: DNA; Ebola virus; adeno-associated virus; adenovirus; prime-boost; vaccine