Laboratory of Malaria Immunology & Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Université de Paris, MERIT, IRD, F-75006 Paris, France.
Expert Rev Vaccines. 2021 Feb;20(2):215-226. doi: 10.1080/14760584.2021.1878029. Epub 2021 Feb 4.
Several malaria vaccines are under various phases of development with some promising results. In placental malaria (PM) a deliberately anti-disease approach is considered as many studies have underlined the key role of VAR2CSA protein, which therefore represents the leading vaccine candidate. However, evidence indicates that VAR2CSA antigenic polymorphism remains an obstacle to overcome. This review analyzes the progress made thus far in developing a VAR2CSA-based vaccine, and addresses the current issues and challenges that must be overcome to develop an effective PM vaccine. Phase I trials of PAMVAC and PRIMVAC VAR2CSA vaccines have shown more or less satisfactory results with regards to safety and immunogenicity. The second generation of VAR2CSA-based vaccines could benefit from optimization approaches to broaden the activity spectrum against various placenta-binding isolates through continued advances in the structural understanding of the interaction with CSA.
几种疟疾疫苗正在不同的开发阶段，有些疫苗的结果很有前景。在胎盘疟疾（PM）中，人们认为采用有针对性的抗病方法是合适的，因为许多研究强调了 VAR2CSA 蛋白的关键作用，因此该蛋白成为了主要的疫苗候选物。然而，有证据表明，VAR2CSA 抗原的多态性仍然是一个需要克服的障碍。这篇综述分析了目前在开发基于 VAR2CSA 的疫苗方面所取得的进展，并讨论了为开发有效的 PM 疫苗而必须克服的当前问题和挑战。PAMVAC 和 PRIMVAC VAR2CSA 疫苗的 I 期临床试验在安全性和免疫原性方面或多或少都取得了令人满意的结果。第二代基于 VAR2CSA 的疫苗可以通过继续深入了解与 CSA 的相互作用的结构，优化方法来拓宽针对各种胎盘结合分离株的活性谱，从而从中受益。
