Genome Replication-Incompetent Sendai Virus Vaccine Vector Against Respiratory Viral Infections That Is Capable of Eliciting a Broad Spectrum of Specific Immune Response

Vaccines have proven to be the most effective measure against infectious diseases. However, not every infectious disease can be prevented by vaccination at the present time. For some diseases, new vaccination strategies have to be developed because classical approaches have not been successful. Viral vectors represent one novel strategy to develop specifically designed recombinant vaccines. Many vaccines have to be applied to certain risk groups among the population that represent large parts of the population, such as infants, children, the elderly, or people with a compromised immune system. Because of the altered competence of the immune system of such individuals, the safety issue is of prime importance. In the case of viral vector-based vaccines, safety will be increased if they are rendered fully replication deficient because replication deficiency does not allow vector spreading and persistence within the vaccinees or mutation toward a more pathogenic variant. In the present chapter we first take up, as an example, respiratory syncytial virus (RSV) to discuss the past problems and future options in its vaccine development. We then illustrate our efforts to develop a genome replication-deficient Sendai virus (SeV) vaccine vector. Three essential prerequisites had to be met by such a vector: (1) complete genome replication deficiency while still being able to efficiently express the inserted vaccine antigen genes; (2) stability of viral genome and encoded trans-genes; and (3) production of the replication-deficient vector stock to a sufficiently high titer in a trans-complementing cell culture system.