|Huntimer, Lucas -|
|Ross, Kathleen -|
|Carrillo-Conde, Brenda -|
|Pruisner, Lynn -|
|Wang, Chong -|
|Narasimhan, Balaji -|
|Wannemuehler, Michael -|
|Ramer-Tait, Amanda -|
Submitted to: Biomedical Materials Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: August 10, 2012
Publication Date: January 1, 2013
Citation: Huntimer, L., Wilson-Welder, J.H., Ross, K., Carrillo-Conde, B., Pruisner, L., Wang, C., Narasimhan, B., Wannemuehler, M.J., Ramer-Tait, A.E. 2013. Single immunization with a suboptimal antigen dose encapsulated into polyanhydride microparticles promotes high titer and avid antibody responses. Biomedical Materials Research. 101(1):91-98. Interpretive Summary: Adjuvants are used in humans and animals to enhance immune responses after vaccination. In this experiment, microparticle adjuvants were evaluated for their ability to increase immune responses of mice. Vaccination of mice with ovalbumin encapsulated in polyanhydride microparticles induced antibody responses at lower dosages as compared to responses of mice receiving ovalbumin administered alone. Antibodies produced by microparticle formulations had greater binding to ovalbumin when compared to responses of mice vaccinated with ovalbumin that was not encapsulated in microparticles. These results suggest that polyanhydride microparticles are an effective adjuvant for increasing immune responses after vaccination. The results of this study will be of interest to scientists, commercial firms, and stakeholders that are interested in producing more immunogenic vaccines.
Technical Abstract: Microparticle adjuvants based on biodegradable polyanhydrides were used to provide controlled delivery of a model antigen, ovalbumin (Ova), to mice. Ova was encapsulated into two different polyanhydride microparticle formulations to evaluate the influence of polymer chemistry on the nature and magnitude of the humoral immune response following administration of a suboptimal dose. Subcutaneous administration of a single dose of polyanhydride microparticles containing 25 µg of Ova elicited humoral immune responses that were comparable in magnitude to that induced by soluble doses of 400 to 1600 µg Ova, demonstrating at least a 16-fold dose-sparing capability. In contrast, the avidity of the Ovaspecific antibodies was greater in mice administered the microparticle formulations in comparison to the soluble doses. The increased avidity was maintained throughout the 12 weektime period. Finally, the microparticle delivery system primed an anamnestic immune response as evidenced by the significant increases in Ova-specific antibody when mice were administered an antigenic challenge of 25 µg of Ova at 12 weeks post-vaccination. Together, these results indicate that encapsulation of antigens into polyanhydride microparticles facilitates isotype switching, establishes immunologic memory and provides a dosage sparing benefit as characterized by a higher quality antibody response.