Enhancement of subunit vaccine delivery with zinc-carnosine coordination polymer through the addition of mannan

• Published in: International journal of pharmaceutics Vol. 656; p. 124076
• Main Authors: Roque, John A., Lukesh, Nicole Rose, Hendy, Dylan A., Dixon, Timothy A., Islam, Md Jahirul, Ontiveros-Padilla, Luis, Pena, Erik S., Lifshits, Liubov M., Simpson, Sean R., Batty, Cole J., Bachelder, Eric M., Ainslie, Kristy M.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 10.05.2024
• Subjects: Adjuvant; Adjuvants, Immunologic - administration & dosage; Adjuvants, Immunologic - chemistry; Animals; Carnosine - administration & dosage; Carnosine - chemistry; Drug Carriers - chemistry; Female; Immunoglobulin G - blood; Mannans - administration & dosage; Mannans - chemistry; Mannans - immunology; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Ovalbumin; Ovalbumin - administration & dosage; Ovalbumin - immunology; Polymers - administration & dosage; Polymers - chemistry; Vaccine; Vaccines, Subunit - administration & dosage; Vaccines, Subunit - immunology; Yeast mannan; Zinc - administration & dosage; Zinc - chemistry; Ovalbumin; Yeast mannan; Adjuvant; Vaccine
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2024.124076

[Display omitted] Vaccines represent a pivotal health advancement for preventing infection. However, because carrier systems with repeated administration can invoke carrier-targeted immune responses that diminish subsequent immune responses (e.g., PEG antibodies), there is a continual need to develop novel vaccine platforms. Zinc carnosine microparticles (ZnCar MPs), which are composed of a one-dimensional coordination polymer formed between carnosine and the metal ion zinc, have exhibited efficacy in inducing an immune response against influenza. However, ZnCar MPs’ limited suspendability hinders clinical application. In this study, we address this issue by mixing mannan, a polysaccharide derived from yeast, with ZnCar MPs. We show that the addition of mannan increases the suspendability of this promising vaccine formulation. Additionally, since mannan is an adjuvant, we illustrate that the addition of mannan increases the antibody response and T cell response when mixed with ZnCar MPs. Mice vaccinated with mannan + OVA/ZnCar MPs had elevated serum IgG and IgG1 levels in comparison to vaccination without mannan. Moreover, in the mannan + OVA/ZnCar MPs vaccinated group, mucosal washes demonstrated increased IgG, IgG1, and IgG2c titers, and antigen recall assays showed enhanced IFN-γ production in response to MHC-I and MHC-II immunodominant peptide restimulation, compared to the vaccination without mannan. These findings suggest that the use of mannan mixed with ZnCar MPs holds potential for subunit vaccination and its improved suspendability further promotes clinical translation.