Journal of Vaccines & Vaccination

Mucosal immunization with an unadjuvanted vaccine that targets S. pneumoniae PspA to human Fc?RI protects against Pneumococcal infection via complement- and Lactoferrin-Mediated Bactericidal Activity

International Conference & Exhibition on Vaccines & Vaccination

22-24 Nov 2011 Philadelphia Airport Marriott, USA

Edmund J. Gosselin, Constantine Bitsaktsis and Bibiana Iglesias

Scientific Tracks Abstracts: J Vaccines Vaccin

Abstract:

Targeting antigen (Ag) to Fc receptors (FcR) can enhance the immune response to Ag in the absence of adjuvant. Furthermore, we recently demonstrated that intranasal (i.n.) immunization with FcR-targeted Ag enhances protection against a Category A intracellular mucosal pathogen, Francisella tularensis . To determine if a similar strategy could be applied to the important pathogen Streptococcus pneumoniae , we used an improved mucosal FcR-targeting strategy that specifi cally targets only human FcgR Type I (hFcgRI). A humanized single chain antibody (Ab) component in which the variable domain binds to hFcgRI [anti-hFcgRI (H22)] was linked in a fusion protein to pneumococcal surface protein A (PspA). PspA is known to elicit protection against pneumococcal sepsis, carriage, and pneumonia in mouse models when administered with adjuvants. Anti-hFcgRI-PspA or rPspA alone were used to immunize i.n. wildtype (WT) and hFcgRI transgenic (Tg) mice in the absence of adjuvant. Th e hFcgRI Tg mice receiving anti-hFcgRI-PspA exhibited elevated S. pneumoniae -specifi c IgA, IgG2c, and IgG1 Ab in sera and bronchoalveolar lavage. Neither immunogen was eff ective in protecting WT mice in the absence of adjuvant, but when PspA was targeted to hFcgRI as the anti-hFcgRI- PspA fusion, enhanced protection against lethal S. pneumoniae challenge was observed in the hFcgRI Tg mice, as compared to mice given non-targeted rPspA alone. Immune sera from the anti-hFcgRI-PspA-immunized Tg mice showed enhanced complement C3 deposition on bacterial surfaces and protection was dependent upon an active complement system. Immune sera also showed enhanced lactoferrin-bactericidal activity directed against S. pneumoniae. Th ese studies were supported by NIH grants R01AI07640801 and R21AI06547601

Biography :

Edmund Gosselin received his Ph.D. in Medical Sciences at the University of Massachusetts, Worcester, MA, in 1988. He completed a postdoctoral fellowship at Dartmouth Medical School in 1993, where he focused on targeting Ag to FcR on APC to enhance T cell activation. Dr. Gosselin then moved to Albany Medical College, where his research has focused on the development of FcR-targeted immunogens as an adjuvant-independent approach for mucosal vaccination. In 2008, he published the fi rst paper demonstrating that immunogens targeted to FcR intranasally can enhance protection against subsequent challenge with a mucosal Category A intracellular pathogen, F. tularensis