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ARS Home » Midwest Area » Ames, Iowa » National Animal Disease Center » Infectious Bacterial Diseases Research » Research » Publications at this Location » Publication #330132
Title: Defective anti-polysaccharide IgG vaccine responses in IgA deficient mice

Author
item FURUYA, YOICHI - Albany Medical College
item KIRIMANJESWARA, GIRISH - Albany Medical College
item ROBERTS, SEAN - Albany Medical College
item RACINE, RACHAEL - Albany Medical College
item WILSON-WELDER, JENNIFER
item SANFILIPPO, ALAN - Albany Medical College
item SALMON, SHARON - Albany Medical College
item METZGER, DENNIS - Albany Medical College

Submitted to: Vaccine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/31/2016
Publication Date: 9/1/2017
Citation: Furuya, Y., Kirimanjeswara, G., Roberts, S., Racine, R., Wilson-Welder, J.H., Sanfilippo, A., Salmon, S., Metzger, D.W. 2017. Defective anti-polysaccharide IgG vaccine responses in IgA deficient mice. Vaccine. 35(37):4997-5005. https://doi.org/10.1016/j.vaccine.2017.07.071.
DOI: https://doi.org/10.1016/j.vaccine.2017.07.071

Interpretive Summary: IgA deficiency is the most common immunodefciency, affecting as many as 1 in 500 Caucasians. As well as being more suceptable to some infections, IgA deficient patients also are poor responders to some types of vaccines, specifically to the polysaccharide component of the Hib and pneumococcal vaccines. In addition to defects in IgA production, these patients also have defective responses in some IgG classes. This is characterized in the presented IgA deficient mouse model. These studies showed that mice deficient in IgA did not respond to vaccination and were more suceptable to infection. Additional studies showed that the B cells werepoorly activated due to the altered gut environemnt in the IgA deficient mouse. Vaccine responses and protection from infection could be enhanved by the cytokine BAFF, providing a possible mechanism for enhancing human vaccine response in patients with this type of immunodeficiency.

Technical Abstract: IgA deficient patients often show defects in antibody responses following immunization with polysaccharide vaccines. We now show that IgA-/- mice exhibit specific defects in IgG antibody responses to various polysaccharide vaccines, but not protein vaccines. Defects in anti-polysaccharide IgG responses were observed even after inoculation of polysaccharide-protein conjugate vaccines to elicit heightened T cell help, while IgG antibody responses to the protein component remained normal. In agreement with these findings, IgA-/- mice were protected from pathogen challenge with protein- but not polysaccharide-based vaccines. Interestingly, after immunization with live bacteria, IgA+/+ and IgA-/- mice were both resistant to lethal challenge and their IgG anti-polysaccharide antibody responses were comparable. Immunization with live bacteria, but not purified polysaccharide, induced production of serum B cell-activating factor (BAFF), a cytokine important for IgG class switching; supplementing IgA-/- cell cultures with BAFF enhanced in vitro polyclonal IgG production. Taken together, these findings show that IgA deficiency impairs IgG class switching following vaccination with polysaccharide antigens and that live bacterial immunization can overcome this defect.