Create New Ways to Induce Mucosal Immunity (Round 3)

Roadblock:

There is an urgent need for new interventions that safely induce long-lasting immune responses at mucosal surfaces. For many diseases in the developing world, including diarrhea, HIV/AIDS, pneumonia, tuberculosis and many others, mucosal surfaces are either the portal of entry for the pathogen into the human body, or are the site at which important immune responses are coordinated. In addition, issues such as previous or concurrent infections and inadequate nutrition may present confounding factors which modulate immunity in mucosa.

What We Are Looking For:

Depending on the pathogen and its interaction with the host, mucosal immune responses may or may not contribute to protection or reduced disease transmission. The goal of this topic, however, is to radically improve the fundamental understanding of the induction of immunity at mucosal surfaces and discover general methods to achieve this immunity. We seek proposals that are "off the beaten track," daring in premise, and clearly different from the approaches currently being developed or employed. 

Note: Specific vaccine concepts for diarrhea, HIV, malaria, pneumonia, and TB should be submitted under "Create New Vaccines for Diarrhea, HIV, Malaria, Pneumonia, and TB." Specific vaccine concepts for diseases or conditions outside the scope of our global health program’s priority disease areas will also be excluded.

A few of the many options to be considered include:

• Use of novel formulation and vaccine delivery technologies that enhance the induction of functional, long-lived mucosal immune responses;
• General and broadly applicable approaches to immune intervention that overcome chronic stimulation, tolerance, negative regulation, or early senescence of immunological effectors in children in the developing world;
• Elucidating the mechanisms involved in the induction of host systemic and mucosal responses as a result of alternative routes of delivery, in addition to parenteral vaccination; 
• Understanding the role of microbial flora, co-infections, micronutrients and other environmental factors in the induction and maintenance of mucosal immunity;
• Novel hypotheses on correlates or surrogate markers of mucosal immunity and an approach to validate them; 
• Novel and practical ways to sample and measure mucosal immune function or competence in developing world populations;
• Novel strategies to generate humoral and cellular immune responses in neonate mucosal tissues that are safe and functional.

For this initiative, we will not consider funding for:

• Specific investigations of disease pathogenesis without a clear linkage to a general hypothesis that is testable across multiple diseases; 
• Testing of interventions without a clear hypothesis of the intervention’s role in mediating human immune responses and a plan for how the impact of that intervention on human mucosal immunity will be measured; 
• Pathogen-specific approaches aimed at exploring the potential of mucosal immunization as a way to protect against disease or infection; 
• Common approaches that are incremental advances to the field;
• Concepts previously or currently under clinical investigation without a significant potential to advance our understanding of mechanisms or markers of mucosal immunity;
• Basic epidemiology or burden of disease studies of mucosal pathogens;
• Specific vaccine concepts for diseases outside the scope of our global health program.