Cytosolic dsRNA improves neonatal innate immune responses to adjuvants in use in pediatric vaccines

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

article

Kiva Brennan¹  Simon Craven³  Maria Cheung³  Daniel Kane³  Eleanor Noone²  Joseph O'Callaghan²  Eleanor J Molloy¹  Patrick T Walsh¹  Fionnuala M McAuliffe³  Sarah L Doyle¹ 

[1] National Children's Research Centre, Our Lady's Children's Hospital Crumlin;Department of Clinical Medicine, School of Medicine, Trinity College Dublin;UCD Perinatal Research Centre, Obstetrics & Gynaecology, School of Medicine, University College Dublin, National Maternity Hospital;Department of Paediatrics, School of Medicine, Trinity College Dublin;Coombe Women and Infants University Hospital

关键词: ALUM;    MPLA;    myeloid cell;    Poly(I:C);    RIG-I;    TLR3;   

DOI  :  10.1002/JLB.5A0521-242R

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Pattern recognition receptors (PRRs) of the innate immune system represent the critical front-line defense against pathogens, and new vaccine formulations target these PRR pathways to boost vaccine responses, through activation of cellular/Th1 immunity. The majority of pediatric vaccines contain aluminum (ALUM) or monophosphoryl lipid A (MPLA) as adjuvants to encourage immune activation. Evidence suggests that elements of the innate immune system, currently being targeted for vaccine adjuvanticity do not fully develop until puberty and it is likely that effective adjuvants for the neonatal and pediatric populations are being overlooked due to modeling of responses in adult systems. We recently reported that the activity of the cytosolic nucleic acid (CNA) sensing family of PRRs is strong in cord blood and peripheral blood of young children. This study investigates the function of CNA sensors in subsets of neonatal innate immune cells and shows that myeloid cells from cord blood can be activated to express T cell costimulatory markers, and also to produce Th1 promoting cytokines. CD80 and CD86 were consistently up-regulated in response to cytosolic Poly(I:C) stimulation in all cell types examined and CNA activation also induced robust Type I IFN and low levels of TNFα in monocytes, monocyte-derived macrophages, and monocyte-derived dendritic cells. We have compared CNA activation to adjuvants currently in use (MPLA or ALUM), either alone or in combination and found that cytosolic Poly(I:C) in combination with MPLA or ALUM can improve expression of activation marker levels above those observed with either adjuvant alone. This may prove particularly promising in the context of improving the efficacy of existing ALUM- or MPLA-containing vaccines, through activation of T cell-mediated immunity.

【 授权许可】

CC BY