The effect of Alpha 1 antitrypsin deficiency on vaccine efficacy
Faculty Information
Name:
Dr. Emily Moser
Email
emily.moser@medicine.ufl.edu
Phone
(804) 304-1842
Faculty Department/Division
Pulmonary, Critical Care, and Sleep Medicine
This project is primarily:
Basic
Research Project Description:
Alpha-1 Antitrypsin (AAT) neutralizes extracellular serine proteases to maintain tissue homeostasis. AAT
deficient (AATD) patients experience chronic lung disease and increased incidence of community acquired
pneumonia. Streptococcus pneumoniae is a major cause of community acquired pneumonia, despite the availability of vaccines. AAT knock out (KO) mice are more susceptible to primary infection with S.
pneumoniae, but whether AAT impacts vaccine-mediated protection from pneumonia is largely unknown. The objective of this project is to define the role of AAT in protective immunity after vaccination. The most effective S. pneumoniae vaccines consist of polysaccharides conjugated to proteins antigens. Protein
antigens travel from the injection site to local lymph nodes (LNs) and activate protective T-dependent antibody responses. Serine proteases in LNs degrade protein antigens but are less active in B cell follicles, where protein antigens are stored for weeks on the surface of follicular dendritic cells. Antigen stability is essential for robust T-dependent antibody responses. Overactive serine protease activity in LNs of AATD patients could prematurely degrade protein antigens. Whether AAT protects protein antigens to promote humoral immunity has never been explored. Our recent studies show that AAT promotes humoral immunity to vaccines. After vaccination, AATD mice produce lower titers of antigen-specific antibodies. AAT is expressed in both mouse and human LNs, and protein antigens are less stable in LNs of AATD mice, compared to control mice. These data led us to hypothesize that lack of AAT leads to cleavage of vaccine protein antigens and impaired antibody-mediated protection from pneumococcal pneumonia.
This project aims to define the role of AAT in formation of vaccine-induced protection against pneumococcal pneumonia. We hypothesize that AAT deficiency impairs protective antibody titers and vaccine-mediated protection against streptococcus pneumoniae-induced pneumonia. The medical student will quantify anti-pneumococcal antibody titers in AATD and control patients using an ELISA. The student will also immunize AATD and control mice with polysaccharide and protein conjugate vaccines to S. pneumoniae. Mice will then be challenged with bacterial infection to determine if AAT promotes vaccine-mediated protection against S. pneumoniae. This project is funded by the Alpha1 foundation.
Does this project have an international component or travel?
No