吸附于阳离子脂质体佐剂CAF09的环孢子蛋白(CSP)诱导的强大抗体和CD8 T细胞反应赋予针对实验性啮齿动物疟疾感染的无菌免疫。
Robust antibody and CD8 T-cell responses induced by CSP adsorbed to cationic liposomal adjuvant CAF09 confer sterilizing immunity against experimental rodent malaria infection.
作者信息
Espinosa Diego A, Christensen Dennis, Muñoz Christian, Singh Sanjay, Locke Emily, Andersen Peter, Zavala Fidel
机构信息
Department of Molecular Microbiology and Immunology, Johns Hopkins Malaria Research Institute, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA.
Department of Infectious Disease Immunology, Statens Serum Institut, Copenhagen, Denmark.
出版信息
NPJ Vaccines. 2017;2. doi: 10.1038/s41541-017-0011-y. Epub 2017 Apr 10.
Despite several decades of extensive research, the development of a highly efficacious malaria vaccine has yet to be accomplished. While the RTS,S malaria vaccine candidate shows the potential to prevent a substantial number of clinical malaria cases, significant improvements in protective efficacy are still needed. Multiple studies have shown that RTS,S induces protective antibody and CD4 T-cell responses, but limited or negligible CD8 T cells. In this study, we evaluated the immunogenicity and protective capacity of full-length recombinant circumsporozoite protein (CSP) administered with the novel cationic liposomal adjuvant system CAF09. Using newly developed transgenic rodent malaria parasites expressing the full-length CSP, we demonstrate that this liposome-based protein-in-adjuvant formulation is capable of inducing robust antibody and CD8 T-cell responses that strongly inhibit parasite infection and development of liver stages, conferring durable sterilizing immunity. These findings underscore the potential of liposome-based adjuvants for inducing robust humoral and CD8 T-cell responses and warrant further studies toward the development of novel subunit vaccine formulations with this adjuvant system.
尽管经过了几十年的广泛研究,但高效疟疾疫苗的研发仍未完成。虽然RTS,S疟疾候选疫苗显示出预防大量临床疟疾病例的潜力,但仍需要大幅提高其保护效力。多项研究表明,RTS,S能诱导保护性抗体和CD4 T细胞反应,但诱导的CD8 T细胞有限或可忽略不计。在本研究中,我们评估了与新型阳离子脂质体佐剂系统CAF09联合使用的全长重组环子孢子蛋白(CSP)的免疫原性和保护能力。利用新开发的表达全长CSP的转基因啮齿动物疟原虫,我们证明这种基于脂质体的佐剂蛋白制剂能够诱导强烈的抗体和CD8 T细胞反应,有力地抑制寄生虫感染和肝期发育,赋予持久的无菌免疫力。这些发现突出了基于脂质体的佐剂诱导强烈体液和CD8 T细胞反应的潜力,并为使用该佐剂系统开发新型亚单位疫苗制剂的进一步研究提供了依据。