AUTHOR=Gogoi Himanshu , Mansouri Samira , Katikaneni Divya S. , Jin Lei 

TITLE=New MoDC-Targeting TNF Fusion Proteins Enhance Cyclic Di-GMP Vaccine Adjuvanticity in Middle-Aged and Aged Mice

JOURNAL=Frontiers in Immunology

VOLUME=Volume 11 - 2020

YEAR=2020

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.01674

DOI=10.3389/fimmu.2020.01674

ISSN=1664-3224

ABSTRACT=Cyclic dinucleotides (CDNs) are promising vaccine adjuvants inducing balanced, potent humoral and cellular immune responses. How ageing influences CDNs' efficacy is unclear. We examined the vaccine efficacy of cyclic di-GMP (CDG), the founding member of CDNs, in 1-year-old (middle-aged), and 2-year-old (aged) C57BL/6J mice. We found that 1-year-old and 2-year-old C57BL/6J mice are defective in CDG-induced memory Th1 and Th17 responses and high-affinity serum IgG, mucosal IgA production. Next, we generated two novel TNF fusion proteins that target soluble TNF and transmembrane TNF to monocyte-derived DCs (moDCs) to enhance CDG vaccine efficacy in 1-year-old and 2-year-old mice. The moDCs-targeting TNF fusion proteins restored CDG-induced memory Th1, Th17, and high-affinity IgG, IgA responses in the 1-year-old and 2-year-old mice. Together, the data suggested that ageing negatively impacts CDG vaccine adjuvanticity. moDCs-targeting TNF fusion proteins enhanced CDG adjuvanticity in the ageing mice.