Pendyala Geetanjali, Calvo-Calle J Mauricio, Moreno Alberto, Kane Ravi S
School of Chemical & Biomolecular Engineering Georgia Institute of Technology Atlanta Georgia 30332 USA.
Department of Pathology University of Massachusetts Medical School Worcester Massachusetts 01655 USA.
Bioeng Transl Med. 2023 Mar 28;8(4):e10514. doi: 10.1002/btm2.10514. eCollection 2023 Jul.
() malaria continues to cause considerable morbidity and mortality worldwide. The circumsporozoite protein (CSP) is a particularly attractive candidate for designing vaccines that target sporozoites-the first vertebrate stage in a malaria infection. Current CSP-based vaccines, however, do not include epitopes that have recently been shown to be the target of potent neutralizing antibodies. We report the design of a SpyCatcher-mi3-nanoparticle-based vaccine presenting multiple copies of a chimeric CSP (cCSP) antigen that incorporates these important "T1/junctional" epitopes as well as a reduced number of (NANP) repeats. cCSP-SpyCatcher-mi3 was immunogenic in mice eliciting high and durable IgG antibody levels as well as a balanced antibody response against the T1/junctional region and the (NANP) repeats. Notably, the antibody concentration elicited by immunization was significantly greater than the reported protective threshold defined in a murine challenge model. Refocusing the immune response toward functionally relevant subdominant epitopes to induce a more balanced and durable immune response may enable the design of a more effective second generation CSP-based vaccine.
疟疾在全球范围内仍导致相当高的发病率和死亡率。环子孢子蛋白(CSP)是设计针对子孢子(疟疾感染的首个脊椎动物阶段)疫苗的极具吸引力的候选物。然而,目前基于CSP的疫苗并不包含最近被证明是强效中和抗体靶点的表位。我们报告了一种基于SpyCatcher-mi3纳米颗粒的疫苗的设计,该疫苗呈现嵌合CSP(cCSP)抗原的多个拷贝,该抗原包含这些重要的“T1/连接区”表位以及数量减少的(NANP)重复序列。cCSP-SpyCatcher-mi3在小鼠中具有免疫原性,可引发高且持久的IgG抗体水平,以及针对T1/连接区和(NANP)重复序列的平衡抗体反应。值得注意的是,免疫引发的抗体浓度显著高于小鼠攻击模型中定义的报告保护阈值。将免疫反应重新聚焦于功能相关的亚显性表位以诱导更平衡和持久的免疫反应,可能有助于设计出更有效的第二代基于CSP的疫苗。