佐剂
免疫系统
埃利斯波特
接种疫苗
抗体
体液免疫
病毒学
免疫学
生物
记忆B细胞
免疫
B细胞
T细胞
作者
Sandra L. Giannini,Emmanuel Hanon,Philippe Moris,Marcelle Van Mechelen,Sandra Morel,Francis Dessy,Marc Fourneau,Brigitte Colau,JoAnn Suzich,Genevieve Losonksy,Marie-Thérèse Martin,Gary Dubin,Martine Wettendorff
出处
期刊:Vaccine
[Elsevier]
日期:2006-08-14
卷期号:24 (33-34): 5937-5949
被引量:452
标识
DOI:10.1016/j.vaccine.2006.06.005
摘要
An effective virus-like particle (VLP) based prophylactic vaccine designed to protect against persistent infection with human papillomavirus (HPV) types 16 and 18 and subsequent lesion development will need to induce a strong humoral and cellular immune response capable of providing long-term protection. Our objective was to evaluate the ability of an HPV16/18 L1 VLP vaccine formulated with the AS04 adjuvant system (3-O-desacyl-4'-monophosphoryl lipid A (MPL) and aluminium salt) to induce an immune response of higher magnitude and persistence compared to a vaccine formulated with aluminium salt only. We demonstrated that MPL adsorbed onto aluminium salt retains its capacity to activate an innate immune response as assessed by the production of TNFalpha by human monocytes (U937). In addition, vaccination of mice, monkeys or human subjects with AS04 formulations induced higher total anti-L1 VLP16 and L1 VLP18 antibody responses (1.6-8.5-fold) than the aluminium salt only formulations. The enhanced antibody response induced by the AS04 vaccine formulation (1.6-4.1-fold) in monkeys and humans was shown to be targeted to functional neutralising L1 VLP16 and L1 VLP18 epitopes as assessed by V5/J4 specific ELISAs or HPV16 and HPV18 pseudo-neutralization assays. The enhanced immune profile observed with the AS04 formulation in terms of both total, V5/J4 specific and neutralizing antibodies was shown to persist for at least 3.5-year post-vaccination in human subjects. Finally, using the newly developed B cell ELISPOT assay we also demonstrated that the AS04 formulation elicited an increased frequency (2.2-5.2-fold) of HPV L1 VLP specific memory B cells when compared with the aluminium salt only formulations. These data strongly support the role of the AS04 adjuvant, which includes the immunostimulant MPL, in triggering a persistent vaccine-induced immune response of high quality.
科研通智能强力驱动
Strongly Powered by AbleSci AI