PDF(Pubmed)
Abstract：
BACKGROUND: Globally, malaria continues to pose a major health challenge, with approximately 247 million cases of the illness and 627,000 deaths reported in 2021. However, the threat is particularly pronounced in sub-Saharan African countries, where pregnant women and children under the age of five face heightened vulnerability to the disease. As a result, the imperative to develop malaria vaccines especially for these vulnerable populations, remains crucial in the pursuit of malaria eradication. However, despite decades of research, effective vaccine development faces technical challenges, including the rapid spread of drug-resistant parasite strains, the complex parasite lifecycle, the development of liver hypnozoites with potential for relapse, and evasion of the host immune system. This review aims to discuss the different malaria vaccine candidates in the pipeline, highlighting different approaches used for adjuvating these candidates, their benefits, and outcomes, and summarizing the progress of these vaccine candidates under development.
METHODS: A comprehensive web-based search for peer-reviewed journal articles published in SCOPUS, MEDLINE (via PubMed), Science Direct, WHO, and Advanced Google Scholar databases was conducted from 1990 to May 2022. Context-specific keywords such as \"Malaria\", \"Malaria Vaccine\", \"Malaria Vaccine Candidates\", \"Vaccine Development\", \"Vaccine Safety\", \"Clinical Trials\", \"mRNA Vaccines\", \"Viral Vector Vaccines\", \"Protein-based Vaccines\", \"Subunit Vaccines\", \"Vaccine Adjuvants\", \"Vaccine-induced Immune Responses\", and \"Immunogenicity\" were emphatically considered. Articles not directly related to malaria vaccine candidates in preclinical and clinical stages of development were excluded.
RESULTS: Various approaches have been studied for malaria vaccine development, targeting different parasite lifecycle stages, including the pre-erythrocytic, erythrocytic, and sexual stages. The RTS, S/AS01 vaccine, the first human parasite vaccine reaching WHO-listed authority maturity level 4, has demonstrated efficacy in preventing clinical malaria in African children. However, progress was slow in introducing other safe, and feasible malaria vaccines through clinical trials . Recent studies highlight the potential effectiveness of combining pre-erythrocytic and blood-stage vaccines, along with the advantages of mRNA vaccines for prophylaxis and treatment, and nonstructural vaccines for large-scale production.
CONCLUSIONS: Malaria vaccine candidates targeting different lifecycle stages of the parasite range from chemoprophylaxis vaccination to cross-species immune protection. The use of a multi-antigen, multi-stage combinational vaccine is therefore essential in the context of global health. This demands careful understanding and critical consideration of the long-term multi-faceted interplay of immune interference, co-dominance, complementary immune response, molecular targets, and adjuvants affecting the overall vaccine-induced immune response. Despite challenges, advancements in clinical trials and vaccination technology offer promising possibilities for novel approaches in malaria vaccine development.
METHODS: A comprehensive web-based search for peer-reviewed journal articles published in SCOPUS, MEDLINE (via PubMed), Science Direct, WHO, and Advanced Google Scholar databases was conducted from 1990 to May 2022. Context-specific keywords such as \"Malaria\", \"Malaria Vaccine\", \"Malaria Vaccine Candidates\", \"Vaccine Development\", \"Vaccine Safety\", \"Clinical Trials\", \"mRNA Vaccines\", \"Viral Vector Vaccines\", \"Protein-based Vaccines\", \"Subunit Vaccines\", \"Vaccine Adjuvants\", \"Vaccine-induced Immune Responses\", and \"Immunogenicity\" were emphatically considered. Articles not directly related to malaria vaccine candidates in preclinical and clinical stages of development were excluded.
RESULTS: Various approaches have been studied for malaria vaccine development, targeting different parasite lifecycle stages, including the pre-erythrocytic, erythrocytic, and sexual stages. The RTS, S/AS01 vaccine, the first human parasite vaccine reaching WHO-listed authority maturity level 4, has demonstrated efficacy in preventing clinical malaria in African children. However, progress was slow in introducing other safe, and feasible malaria vaccines through clinical trials . Recent studies highlight the potential effectiveness of combining pre-erythrocytic and blood-stage vaccines, along with the advantages of mRNA vaccines for prophylaxis and treatment, and nonstructural vaccines for large-scale production.
CONCLUSIONS: Malaria vaccine candidates targeting different lifecycle stages of the parasite range from chemoprophylaxis vaccination to cross-species immune protection. The use of a multi-antigen, multi-stage combinational vaccine is therefore essential in the context of global health. This demands careful understanding and critical consideration of the long-term multi-faceted interplay of immune interference, co-dominance, complementary immune response, molecular targets, and adjuvants affecting the overall vaccine-induced immune response. Despite challenges, advancements in clinical trials and vaccination technology offer promising possibilities for novel approaches in malaria vaccine development.
摘要：
背景：在全球范围内，疟疾继续构成重大的健康挑战，2021年报告了大约2.47亿例这种疾病和62.7万人死亡。然而,这种威胁在撒哈拉以南非洲国家尤为明显，孕妇和五岁以下的儿童面临更高的疾病脆弱性。因此,必须开发疟疾疫苗，特别是针对这些脆弱人群，在追求根除疟疾方面仍然至关重要。然而,尽管进行了几十年的研究,有效的疫苗开发面临技术挑战，包括耐药寄生虫菌株的快速传播，复杂的寄生虫生命周期，有可能复发的肝脏催生子的发展，和宿主免疫系统的逃避。这篇综述旨在讨论正在开发的不同疟疾疫苗候选产品，强调用于佐剂化这些候选物的不同方法，他们的好处,和结果，并总结了这些正在开发的候选疫苗的进展。
方法：对发表在SCOPUS上的同行评审期刊文章进行全面的基于网络的搜索，MEDLINE（通过PubMed），科学直接，WHO,和高级谷歌学者数据库于1990年至2022年5月进行。特定于上下文的关键字，如“疟疾”，“疟疾疫苗”，“疟疾候选疫苗”，“疫苗开发”，“疫苗安全”，“临床试验”，“mRNA疫苗”，“病毒载体疫苗”，“基于蛋白质的疫苗”，“亚单位疫苗”，“疫苗佐剂”，“疫苗诱导的免疫反应”，和“免疫原性”被着重考虑。不包括与临床前和临床发展阶段的疟疾疫苗候选物直接相关的文章。
结果：已经研究了用于疟疾疫苗开发的各种方法，针对不同的寄生虫生命周期阶段，包括红细胞前病变,红细胞，性阶段。RTS,S/AS01疫苗，首个人类寄生虫疫苗达到世卫组织列出的权威机构4级成熟度，已证明在预防非洲儿童的临床疟疾方面有效。然而,引入其他保险箱的进展缓慢，和通过临床试验可行的疟疾疫苗。最近的研究强调了结合前红细胞和血液阶段疫苗的潜在有效性，连同mRNA疫苗在预防和治疗方面的优势，和大规模生产的非结构性疫苗。
结论：针对寄生虫不同生命周期阶段的疟疾候选疫苗从化学预防疫苗接种到跨物种免疫保护。使用多抗原，因此，多阶段组合疫苗在全球健康背景下至关重要。这需要认真理解和批判性考虑免疫干扰的长期多方面相互作用，共同支配,互补免疫反应，分子靶标,和影响总体疫苗诱导的免疫反应的佐剂。尽管面临挑战,临床试验和疫苗接种技术的进步为疟疾疫苗开发的新方法提供了有希望的可能性。
方法：对发表在SCOPUS上的同行评审期刊文章进行全面的基于网络的搜索，MEDLINE（通过PubMed），科学直接，WHO,和高级谷歌学者数据库于1990年至2022年5月进行。特定于上下文的关键字，如“疟疾”，“疟疾疫苗”，“疟疾候选疫苗”，“疫苗开发”，“疫苗安全”，“临床试验”，“mRNA疫苗”，“病毒载体疫苗”，“基于蛋白质的疫苗”，“亚单位疫苗”，“疫苗佐剂”，“疫苗诱导的免疫反应”，和“免疫原性”被着重考虑。不包括与临床前和临床发展阶段的疟疾疫苗候选物直接相关的文章。
结果：已经研究了用于疟疾疫苗开发的各种方法，针对不同的寄生虫生命周期阶段，包括红细胞前病变,红细胞，性阶段。RTS,S/AS01疫苗，首个人类寄生虫疫苗达到世卫组织列出的权威机构4级成熟度，已证明在预防非洲儿童的临床疟疾方面有效。然而,引入其他保险箱的进展缓慢，和通过临床试验可行的疟疾疫苗。最近的研究强调了结合前红细胞和血液阶段疫苗的潜在有效性，连同mRNA疫苗在预防和治疗方面的优势，和大规模生产的非结构性疫苗。
结论：针对寄生虫不同生命周期阶段的疟疾候选疫苗从化学预防疫苗接种到跨物种免疫保护。使用多抗原，因此，多阶段组合疫苗在全球健康背景下至关重要。这需要认真理解和批判性考虑免疫干扰的长期多方面相互作用，共同支配,互补免疫反应，分子靶标,和影响总体疫苗诱导的免疫反应的佐剂。尽管面临挑战,临床试验和疫苗接种技术的进步为疟疾疫苗开发的新方法提供了有希望的可能性。
