Liposome-based polymer complex as a novel adjuvant: enhancement of specific antibody production and isotype switch

Chia-Hung Chen^1,*, Yu-Ling Lin^1,*, Yen-Ku Liu¹, Pei-Juin He², Ching-Min Lin¹, Yi-Han Chiu², Chang-Jer Wu³, Tian-Lu Cheng⁴, Shih-Jen Liu^5,6,**, Kuang-Wen Liao^1,2,**
¹Institute of Molecular Medicine and Bioengineering, ²Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, ³Department of Food Science, National Taiwan Ocean University, Keelung, 4Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, ⁵National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli, ⁶Graduate Institute of Immunology, China Medical University, Taichung, Taiwan, ,
*Chia-Hung Chen and Yu-Ling Lin contributed equally to this work
**Kuang-Wen Liao and Shih-Jen Liu contributed equally to this work

Abstract: The aim of vaccination is to induce appropriate immunity against pathogens. Antibody-mediated immunity is critical for protection against many virus diseases, although it is becoming more evident that coordinated, multifunctional immune responses lead to the most effective defense. Specific antibody (Ab) isotypes are more efficient at protecting against pathogen invasion in different locations in the body. For example, compared to other Ab isotypes, immunoglobulin (Ig) A provides more protection at mucosal areas. In this study, we developed a cationic lipopolymer (liposome-polyethylene glycol-polyethyleneimine complex [LPPC]) adjuvant that strongly adsorbs antigens or immunomodulators onto its surface to enhance or switch immune responses. The results demonstrate that LPPC enhances uptake ability, surface marker expression, proinflammatory cytokine release, and antigen presentation in mouse phagocytes. In contrast to Freund's adjuvant, LPPC preferentially activates Th1-immunity against antigens in vivo. With lipopolysaccharides or CpG oligodeoxynucleotides, LPPC dramatically enhances the IgA or IgG2A proportion of total Ig, even in hosts that have developed Th2 immunities and high IgG1 serum titers. Taken together, the results demonstrate that the LPPC adjuvant not only increases the immunogenicity of antigens but also modulates host immunity to produce an appropriate Ab isotype by combining with immunomodulators.

Keywords: liposome-PEG-PEI complex, adjuvant, class switch, immunomodulator, vaccine