title: Intranasal Sendai viral vector vaccination is more immunogenic than intramuscular under pre-existing anti-vector antibodies.
abstract: Viral vectors are promising vaccine tools for eliciting potent cellular immune responses. Pre-existing anti-vector antibodies, however, can be an obstacle to their clinical use in humans. We previously developed a Sendai virus (SeV) vector vaccine and showed the potential of this vector for efficient CD8(+) T-cell induction in macaques. Here, we investigated the immunogenicity of SeV vector vaccination in the presence of anti-SeV antibodies. We compared antigen-specific CD8(+) T-cell responses after intranasal or intramuscular immunization with a lower dose (one-tenth of that in our previous studies) of SeV vector expressing simian immunodeficiency virus Gag antigen (SeV-Gag) between naive and pre-SeV-infected cynomolgus macaques. Intranasal SeV-Gag immunization efficiently elicited Gag-specific CD8(+) T-cell responses not only in naive but also in pre-SeV-infected animals. In contrast, intramuscular SeV-Gag immunization induced Gag-specific CD8(+) T-cell responses efficiently in naive but not in pre-SeV-infected animals. These results indicate that both intranasal and intramuscular SeV administrations are equivalently immunogenic in the absence of anti-SeV antibodies, whereas intranasal SeV vaccination is more immunogenic than intramuscular in the presence of anti-SeV antibodies. It is inferred from a recent report investigating the prevalence of anti-SeV antibodies in humans that SeV-specific neutralizing titers in more than 70% of people are no more than those at the SeV-Gag vaccination in pre-SeV-infected macaques in the present study. Taken together, this study implies the potential of intranasal SeV vector vaccination to induce CD8(+) T-cell responses even in humans, suggesting a rationale for proceeding to a vaccine clinical trial using this vector.
authors.affiliation: The Institute of Medical Science, The University of Tokyo, Shirokanedai, Tokyo, Japan.
authors.forename: Chikaya
authors.initials: C
authors.lastname: Moriya
authors.forename: Satoshi
authors.initials: S
authors.lastname: Horiba
authors.forename: Kyoko
authors.initials: K
authors.lastname: Kurihara
authors.forename: Takeo
authors.initials: T
authors.lastname: Kamada
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Takahara
authors.forename: Makoto
authors.initials: M
authors.lastname: Inoue
authors.forename: Akihiro
authors.initials: A
authors.lastname: Iida
authors.forename: Hiroto
authors.initials: H
authors.lastname: Hara
authors.forename: Tsugumine
authors.initials: T
authors.lastname: Shu
authors.forename: Mamoru
authors.initials: M
authors.lastname: Hasegawa
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Matano
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004337:Drug Carriers / Q000008:administration & dosage*; D015683:Gene Products, gag / Q000235:genetics / Q000276:immunology; D005822:Genetic Vectors / Q000008:administration & dosage* / Q000276:immunology; D007273:Injections, Intramuscular; D008251:Macaca; D018449:SAIDS Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology*; D029082:Sendai virus / Q000235:genetics / Q000276:immunology; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology
chemical_list: D004337:Drug Carriers; D015683:Gene Products, gag; D018449:SAIDS Vaccines