Controlled analysis of nanoparticle charge on mucosal and systemic antibody responses following pulmonary immunization

Catherine A. Fromen, Gregory R. Robbins, Tammy W. Shen, Marc P. Kai, Jenny P. Y. Ting, and Joseph M. DeSimone

Proc Natl Acad Sci USA. (2015) 112: 488-493.

Speaker: Chung-Lin Li (利宗霖)                                  Time: 14:10~15:00, 4/29, 2015

Commentator: Dr. Ai-Li Shiau (蕭璦莉老師)             Place: Room 601

Abstract

    Most infectious agents enter the body at mucosal surfaces and therefore mucosal immune responses function as a first line of defense (1). Development of mucosal vaccines not only provide local protection but also confer systemic immunity. Nanoparticles (NP) are used as either a delivery system to enhance antigen processing or as an immunostimulant adjuvant to activate or enhance immunity (2). In this study, the authors wanted to know whether NP surface charge plays a role in inducing mucosal immune responses. First, they used the Particle Replication in Non-Wetting Template (PRINT) process to synthesize hydrogel NPs that have constant size, shape, and antigen loading but different only in surface charge. The authors treated bone marrow-derived dendritic cells (BMDCs) with (ζ⁺)NP-OVA or (ζ^-)NP-OVA and tested their ability to induce antigen-specific T-cell proliferation. The results indicated that BMDCs treated with (ζ⁺)NP-OVA induced more robust T-cell proliferation than (ζ^-)NP-OVA and soluble OVA alone. Moreover, (ζ⁺)NP-OVA induced higher expression of surface MHCII, CD80 and CD86 than (ζ^-)NP-OVA. The authors also found significant increases in IL-6 and IL-12 cytokine production by BMDCs treated with (ζ⁺)NP-OVA compared with (ζ^-)NP-OVA treatment. In the mouse model, pulmonary immunization with (ζ⁺)NP-OVA increased CD4⁺ T-cell activation and germinal center B-cell expansion in the local lung draining mediastinal lymph nodes. In addition, (ζ⁺)NP-OVA can induce OVA-specific IgG and IgA antibody titers in plasma and bronchoalveolar lavage fluid (BALF) but (ζ^-)NP-OVA only induce low OVA-specific IgG antibody titers in plasma and BALF. These results were independent of endotoxin contamination. In conclusion, this study indicates that surface charge of NPs may play an important role in designing pulmonary vaccines which aid in the development of pulmonary-based vaccine platforms that are applicable to a diverse array of pathogens.

References

1.     Neutra MR, Kozlowski PA (2006). Mucosal vaccines: The promise and the challenge. Nat Rev Immunol 6(2):148–158.

2.     Zhao L, et al. (2014) Nanoparticle vaccines. Vaccine 32(3):327–337.