Engineering immunity in the mucosal niche against sexually transmitted infections

The mucosal surfaces of the genital tract are the site of entry to over 30 different bacterial, parasitic, and viral pathogens that are the cause of sexually transmitted infections (STIs) including HIV. Women and adolescent girls are more severely impacted by STIs than men due in part to a greater biological susceptibility for acquiring infections and differences in disease sequelae. While it is widely accepted that preventative vaccines against the most commonly transmitted STIs would have a major impact on decreasing the global health burden of STIs for women worldwide, several challenges preclude their development. The female genital tract is a complex niche of microflora, hormonal influences, and immune tissues and cells that result in a mucosal immune system that is distinct from other mucosal sites and from our systemic immune system. An appreciation of these differences and their effect on shaping mucosal immunity to sexually transmitted pathogens is an important determinant for the design of effective STI vaccines. Here we describe the anatomy and mucosal immune system of the female reproductive tract, and discuss bioengineering strategies to design mucosal vaccines that overcome delivery challenges and coordinate the presentation kinetics and compartmentalization of antigens and adjuvants to relevant mucosal immune cell subsets. In particular, we describe recent progress in understanding the role of specific mucosal dendritic cell subsets in facilitating immune responses to pathogenic microbes in the genital mucosa. We also discuss the development of pathogen-mimicking materials that may be useful for engineering protective immunity in this mucosal niche.