Uncharted Territory: Early Events After Adenovirus 26-Based Vaccination

Abstract

Vaccines play a crucial role in improving human health by reducing the incidence and mortality of vaccine-preventable diseases, such as diphtheria, smallpox, polio, measles, mumps, and rubella. Vaccines confer protection against specific pathogens by triggering an immune response in the host and they can be produced on different platforms including inactivated or weakened pathogens or toxins, viral vectors (such as adenovirus or modified vaccinia virus Ankara), subunit vaccines, and genetic vaccines (e.g., mRNA vaccines). Adenovirus-based vaccines encode one or more disease-specific transgenes to induce immunity against the target disease. Adenoviral vectors present certain characteristics that make them excellent vaccine platforms, such as the induction of transgene-specific immunity, large packaging capacity (up to 35 kbp of transgenic sequence), and broad tropism. In the field of prophylactic vaccines, the use of adenoviral vectors is limited to non-replicating vectors. These vectors are engineered through genetic modifications of the virus to produce a non-replicating virion that can carry a transgene of interest. Adenovirus-based vaccines elicit strong immune responses against the transgene that they carry and these immune responses depend heavily on early events following vaccination. In this dissertation, we study early events after adenovirus-based vaccination to understand their role in shaping adaptive immune responses and the development of adverse effects.