Institute for Glycomics, Griffith University, Gold Coast, Qld., Australia.
Immunol Rev. 2020 Jan;293(1):270-282. doi: 10.1111/imr.12819. Epub 2019 Nov 10.
After many decades of research, an effective vaccine for malaria is still not available. Most research efforts have focused on identifying a key target antigen and then using powerful adjuvants to generate specific antibodies that can block parasites from entering host cells (hepatocytes, red blood cells). However, the inability to generate sufficiently potent antibody responses has led to significant disappointment with current vaccine programs. An additional challenge for sub-unit vaccines is that key vaccine antigens are highly polymorphic. These challenges have spurred radically different approaches to malaria vaccine development. Many of these involve the use of "whole parasites"-either extracted from mosquitoes or cultured. With these, every parasite molecule for that particular strain is included in the vaccine. This strategy is showing great promise following several clinical trials with irradiated sporozoites. However, a whole-parasite approach to a blood stage vaccine has not advanced as quickly. This article outlines the history, the different approaches that are being taken and the challenges associated with whole parasite blood stage vaccines and discusses recent exciting developments as these vaccines now move into the clinic.
经过几十年的研究，仍没有疟疾的有效疫苗。大多数研究工作都集中在确定一个关键的靶抗原，然后使用强大的佐剂来产生特异性抗体，以阻止寄生虫进入宿主细胞（肝细胞、红细胞）。然而，由于无法产生足够有效的抗体反应，目前的疫苗项目令人非常失望。亚单位疫苗的另一个挑战是关键疫苗抗原高度多态性。这些挑战促使人们对疟疾疫苗的开发采取了截然不同的方法。其中许多方法涉及使用“完整寄生虫”-要么从蚊子中提取，要么培养。在这些方法中，特定菌株的每一个寄生虫分子都包含在疫苗中。这一策略在经过几项辐照子孢子的临床试验后显示出巨大的希望。然而，全寄生虫血阶段疫苗的方法并没有那么快得到推进。本文概述了历史、正在采取的不同方法以及与全寄生虫血阶段疫苗相关的挑战，并讨论了这些疫苗现在进入临床阶段的最新令人兴奋的进展。
