Chapter 66 – Filling the Immunological Gap: Recombinant Viral Vectors for Mucosal Vaccines

Most pathogens initiate infection via mucosal routes; consequently effective vaccines that induce relevant innate and adaptive immune responses at mucosal sites are required for protection. Indeed, we are confronted by a number of major global infections, such as HIV and tuberculosis, that have complex methods of pathogenesis, that can be antigenically diverse, and that evolved significant mechanisms to evade human immune responses. The challenge for producing vaccines against these agents is knowing the type of immune responses critical for control of infection. The use of recombinant viral vectors provides a novel approach for delivering genes encoding antigens of a different pathogen as a vaccine. Here we aim to provide an overview of recombinant viral vectors that can be utilized for mucosal immunization and a current review of outcomes of human trials involving these viral vectors. Although RV144 was marginally effective, there were also setbacks in HIV vaccine trials involving Ad5 vectors. Importantly, exciting progress has been made in identification of novel vectors that induce local mucosal control of early infection and significantly improve the breadth of T cell-mediated responses. Indeed, findings concerning local mucosal control of HIV and TB are merging into a comparable storyline that may offer control of these pathogens.