Streptococcus pneumoniae is a major cause of life?threatening diseases such as pneumonia, meningitis and sepsis. The World Health Organization estimates that at least 1.6 million people die each year from pneumococcal infections. However, pneumococcal infections can be significantly reduced by vaccines that induce antibodies (Abs) reactive against the pneumococcal polysaccharide (PPS) capsule. PPS?specific Abs of the IgG isotype offers the most substantial protection against life?threatenin invasive disease. Thus, eliciting PPS?specific IgG is a major goal of vaccination. The current proposal stems from our striking preliminary data showing that respiratory virus infections in mice and primates can dramatically reduce the quantity of IgG, but increase IgA, produced in response to polysaccharide antigens that were administered several weeks preceding viral infection. We therefore hypothesize that respiratory viral infections may have important physiological consequences for polysaccharide?based vaccine induced?protection against S. pneumoniae and other encapsulated bacteria. Our objectives are to test this hypothesis and define the virus infection?induced signals that modulate polysaccharide?specific Ab responses. In addition, we propose to test the novel hypothesis that virus infection induces Ps?specific Ig??secreting cells to undergo secondary class switch recombination. The results obtained from these studies are expected to provide important clues regarding the viral-induced factors and mechanisms involved in shifting polysaccharide?specific IgG responses to IgA responses, as well as the physiological impact this modulation may have on polysaccharide?based vaccine efficacy in humans.

Public Health Relevance

The goal of the research proposed in the current application is to understand how the immune system is regulated to respond to vaccines against Streptococcus pneumoniae. The knowledge gained from these studies may lead to improved vaccines that provide enhanced protection against pneumococcal infections currently threatening global public health.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AI121947-02
Application #
9244720
Study Section
Immunity and Host Defense (IHD)
Program Officer
Lu, Kristina
Project Start
2016-03-17
Project End
2018-02-28
Budget Start
2017-03-01
Budget End
2018-02-28
Support Year
2
Fiscal Year
2017
Total Cost
$233,719
Indirect Cost
$80,926
Name
Wake Forest University Health Sciences
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
937727907
City
Winston-Salem
State
NC
Country
United States
Zip Code
27157