Create New Ways to Induce and Measure Mucosal Immunity (Round 4)

Roadblock:

There is an urgent need for new interventions that safely induce long-lasting protection against pathogens via specific immune responses at mucosal surfaces. For many diseases prevalent 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 protective immunity or reduced disease transmission. The goal of this topic, however, is to radically improve the fundamental understanding of the induction and measurement of immunity at mucosal surfaces such as the gut, lung, vagina, and nasopharyx. We invite proposals that target the discovery of general methods to achieve and measure this immunity.

Ideas that can be clearly tested in relevant models of disease and where clear comparisons are made over traditional approaches will be given priority. We seek proposals that are "off the beaten track," daring in premise, and clearly different from the approaches currently being developed or employed. 

A few of the many options to be considered include: 

• Novel and practical ways to sample mucosal immune function or competence, and measure functional readouts in developing world populations; 
• 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; 
• Generate and measure mucosal immunity protecting against tropical enteropathic syndromes, particularly as it relates to current understanding of the role of microbial flora, co-infections micronutrient deficiencies, and other environmental factors in the induction and maintenance of mucosal immunity; 
• Simultaneous induction of mucosal and systemic responses through alternative routes of delivery (including parenteral administration) or alternative formulations in comparison to traditional approaches; 
• Novel hypotheses on correlates or surrogate markers of mucosal immunity and an approach to validate them; 
• Novel strategies to generate humoral and cellular immune responses in neonate mucosal tissues that are safe and functional. 

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, without the potential for broader applicability, 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. 

Suggested readings: Nature Reviews Immunology, June 2008, Vol. 8, No 6 
Focus on: Mucosal Immunology (p409-466) 

For information on The Bill & Melinda Gates Foundation’s priority global health conditions, please click here.