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.

Recombinant viral vectors are promising vaccine tools for eliciting potent cellular immune responses against immunodeficiency virus infection, but pre-existing anti-vector antibodies can be an obstacle to their clinical use in humans. We have previously vaccinated rhesus macaques with a recombinant Sendai virus (SeV) vector twice at an interval of more than 1 year and have shown efficient antigen-specific T-cell induction by the second as well as the first vaccination. Here, we have established the method for measurement of SeV-specific neutralizing titers and have found efficient SeV-specific neutralizing antibody responses just before the second SeV vaccination in these macaques. This suggests the feasibility of inducing antigen-specific T-cell responses by SeV vaccination even in the host with pre-existing anti-SeV neutralizing antibodies.