**Conflict of interest**

HCV cross-reactive antibodies and HCV antigen-dependent expression of IFN-γ in T cells from a cohort of HCV-naïve but Ad-immune human individuals. Previous studies have also reported that one pathogen can induce cross-reactive immunity against an unrelated pathogen [91, 208]. This kind of immunity is known as heterologous immunity. Heterologous immunity is a double-edged sword, which can modulate the breadth of the T cell repertoire, influence the memory T cell pool and/or the immune dominance of a specific epitope, and lead to enhanced or diminished immune responses against a pathogen. These observations have significant clinical implications on natural history, immunopathogenesis, and disease outcome in HCV infection. The widespread use of adenoviral vectors in mass vaccination programs might change the immune hierarchy and natural T cell responses against HCV antigens and deviate and/or alter the incidence of HCV infection and immune pathogenesis in an at-risk population. However, a careful evaluation of adenoviral-induced cross-reactive immune responses and their impact on HCV immunity and immunopathology is needed to

Since their first use as gene delivery vehicles, adenoviral vectors have been extensively studied in a number of applications and have improved substantially over time. Issues such as toxicity, pre-existing immunity in humans, and challenges in construction are continually being addressed. More recently, outbreaks of newly emerging infectious diseases, such as SARS, Ebola, and Zika, and the continuing threat of bioterrorism have increased the requirement of novel vaccine platforms which can be designed and produced in large scale within a short period of time. Adenoviral vectors, due to their versatility, ease of construction, adeptness to rapid mass production, and induction of robust transgene-specific humoral and cellular immune responses, have proven to be valuable in the development of vaccines for emerging viral infectious diseases. Furthermore, extensive knowledge about the adenoviral vector biology and the induced immune responses in animals have tremendously helped in developing effective vaccine candidates against several viral pathogens, which have progressed to advanced clinical stages. The adenoviruses are now at the forefront of vaccinology and have shown huge potential in both pre-clinical and clinical studies for HIV, malaria, Ebola virus, and Zika virus vaccines. Apart from infectious disease, adenoviral vectors have been approved for human use as cancer and gene therapy. Therefore, adenoviral vectors have opened new avenues in gene delivery, vaccine antigen delivery, and cancer

We acknowledge Bharti Singh for designing and creating figures for this chapter. This work was supported by the Canadian Institutes of Health Research (CIHR) operating grant to BA

more accurately ascertain the impact of this phenomenon.

**4. Conclusions and future prospects**

molecular therapy.

74 Adenoviruses

(MOP 79327).

**Acknowledgements**

The authors SS, BA, and RK are co-inventors of a patent on adenoviral vector-based method of inducing immune responses against hepatitis C virus.
