Systemic and Mucosal Immune Responses to Cryptosporidium—Vaccine Development

Abstract

Cryptosporidium spp is a major cause of diarrheal disease worldwide, particularly in malnourished children and untreated AIDS patients in developing countries in whom it can cause severe, chronic and debilitating disease. Unfortunately, there is no consistently effective drug for these vulnerable populations and no vaccine, partly due to a limited understanding of both the parasite and the host immune response. In this review, we will discuss our current understanding of the systemic and mucosal immune responses to Cryptosporidium infection, discuss the feasibility of developing a Cryptosporidium vaccine and evaluate recent advances in Cryptosporidium vaccine development strategies

Next Generation Sequencing uncovers within-host differences in the genetic diversity of Cryptosporidium gp60 subtypes

“…For example, vaccine research for Cryptosporidium has focused on proteins involved in attachment to, and invasion of, host cells (Mead 2014;Ludington and Ward, 2015). Therefore, immunisation with predominant antigens could result in vaccine failures in some regions where heterogeneous parasite populations dominate (Grinberg and Widmer, 2016).…”

Cryptosporidium in humans and animals—a one health approach to prophylaxis

“…The development of vaccines for cryptosporidiosis, particularly in vulnerable populations such as children and malnourished populations, is urgent, but has been hampered by an incomplete understanding of the host immune response to Cryptosporidium . Therefore, a better understanding of host–parasite interactions is crucial for the development of an effective vaccine .…”

“…It is known that both innate and adaptive host response are important in the control of Cryptosporidium infection . Yet the nature of these responses, particularly in humans, is not completely understood …”

“…Early mediators of innate immune protection include the thick mucus layer of the small intestine, intestinal epithelial cells and chemokines, cytokines and antimicrobial peptides secreted into the intestinal lumen and/or underlying submucosa and bloodstream . Important cytokines include γ‐interferon (IFN‐γ), which is secreted early in infection by natural killer (NK) cells, macrophages and dendritic cells, which are thought to play a major role in orchestrating both the innate and adaptive immune responses . Th1 inflammatory response and cytokines, such as interleukin 12, 15 and 18, are also important in the resistance and recovery to Cryptosporidium infection .…”

“…The ideal Cryptosporidium vaccine should provide rapid lifelong immunity in all vaccinated individuals, be broadly protective against the most common species and subtypes of Cryptosporidium , prevent disease transmission, and be readily accessible, stable and cheap . Ensuring cross‐reaction against the most common species infecting humans, however, will be difficult, as more than 20 Cryptosporidium species and genotypes can infect humans as discussed above.…”