中文摘要：研究基于最新的疟疾CSP 3D7全长序列合成了一种恶性疟疾蛋白-013（FMP013）疫苗，以C57BL/6小鼠为对象分析了两种新型脂质体佐剂（ALF）对FMP013疫苗的免疫原性的影响。ALF是一种包含合成单磷酰脂A（3D-PHAD (R)）的脂质体。试验分别将FMP013与ALF、FMP013与包含氢氧化铝的ALF（ALFA）、FMP013与包含QS-21的ALF（ALFQ）进行免疫。结果表明，与Montanide佐剂对照组相比，ALF和ALFA能够诱导产生相同的抗体滴度，并提供相同的保护作用；与其它三种佐剂相比，ALFQ效果更优，三次免疫后能够产生更高的抗体滴度，更高的血清IgG2c滴度，并提供更好的保护作用。MP013 + ALFQ能够增加源于脾脏生发中心的活性B细胞数量和抗体分泌细胞的数量；同时MP013 + ALFQ诱导了抗体特异性IFN- γ ELISPOT活性，提高CD41（+）T细胞和T(H)1- 细胞因子浓度。这些研究表明，可溶性环子孢子蛋白与包含QS-21的佐剂ALFQ联用能够诱导产生免疫保护作用。
 
外文摘要：Malaria caused by Plasmodium falciparum continues to threaten millions of people living in the tropical parts of the world. A vaccine that confers sterile and life-long protection remains elusive despite more than 30 years of effort and resources invested in solving this problem. Antibodies to a malaria vaccine candidate circumsporozoite protein (CSP) can block invasion and can protect humans against malaria. We have manufactured the Falciparum Malaria Protein-013 (FMP013) vaccine based on the nearly full-length P. falciparum CSP 3D7 strain sequence. We report here immunogenicity and challenge data on FMP013 antigen in C57BL/6 mice formulated with two novel adjuvants of the Army Liposome Formulation (ALF) series and a commercially available adjuvant Montanide ISA 720 (Montanide) as a control. ALF is a liposomal adjuvant containing a synthetic monophosphoryl lipid A (3D-PHAD (R)). In our study, FMP013 was adjuvanted with ALF alone, ALF containing aluminum hydroxide (ALFA) or ALF containing QS-21 (ALFQ). Adjuvants ALF and ALFA induced similar antibody titers and protection against transgenic parasite challenge that were comparable to Montanide. ALFQ was superior to the other three adjuvants as it induced higher antibody titers with improved boosting after the third immunization, higher serum IgG2c titers, and enhanced protection. FMP013 + ALFQ also augmented the numbers of splenic germinal center-derived activated B-cells and antibody secreting cells compared to Montanide. Further, FMP013 + ALFQ induced antigen-specific IFN-gamma ELISPOT activity, CD41(+) T-cells and a T(H)1-biased cytokine profile. These results demonstrate that soluble CSP can induce a potent and sterile protective immune response when formulated with the QS-21 containing adjuvant ALFQ. Comparative mouse immunogenicity data presented here were used as the progression criteria for an ongoing non-human primate study and a regulatory toxicology study in preparation for a controlled human malaria infection (CHMI) trial. Published by Elsevier Ltd.
外文关键词：Adjuvant； Malaria； Vaccine； Liposomes； ALFQ； Monophosphoryl lipid A； QS-21； Plasmodium falciparum； Circumsporozoite protein； FMP013
作者：Genito, CJ; Beck, Z; Phares, TW; Kalle, F; Limbach, KJ; Stefaniak, ME; Patterson, NB; Bergmann-Leitner, ES; Waters, NC; Matyas, GR; Alving, CR; Dutta, S
作者单位：美国沃尔特陆军研究所
期刊名称：VACCINE
期刊影响因子：3.235
出版年份：2017
出版刊次：7
点击下载：包含单磷酰脂A和QS-21的脂质体是可溶性环子孢子蛋白疟疾疫苗FMP013的有效佐剂