Rathay Veronika, Fürle Kristin, Kiehl Viktoria, Ulmer Anne, Lanzer Michael, Thomson-Luque Richard
Parasitology, Centre for Infectious Diseases, University Hospital Heidelberg, Medical Faculty, Heidelberg University, 69120 Heidelberg, Germany.
Sumaya-Biotech GmbH & Co. KG, 69115 Heidelberg, Germany.
Vaccines (Basel). 2024 Feb 17;12(2):208. doi: 10.3390/vaccines12020208.
Vaccines are highly effective tools against infectious diseases and are also considered necessary in the fight against malaria. Vaccine-induced immunity is frequently mediated by antibodies. We have recently conducted a first-in-human clinical trial featuring SumayaVac-1, a malaria vaccine based on the recombinant, full-length merozoite surface protein 1 (MSP1) formulated with GLA-SE as an adjuvant. Vaccination with MSP1 was safe and elicited sustainable IgG antibody titers that exceeded those observed in semi-immune populations from Africa. Moreover, IgG antibodies stimulated various Fc-mediated effector mechanisms associated with protection against malaria. However, these functionalities gradually waned. Here, we show that the initial two doses of SumayaVac-1 primarily induced the cytophilic subclasses IgG1 and IgG3. Unexpectedly, a shift in the IgG subclass composition occurred following the third and fourth vaccinations. Specifically, there was a progressive transition to IgG4 antibodies, which displayed a reduced capacity to engage in Fc-mediated effector functions and also exhibited increased avidity. In summary, our analysis of antibody responses to MSP1 vaccination unveils a temporal shift towards noninflammatory IgG4 antibodies. These findings underscore the importance of considering the impact of IgG subclass composition on vaccine-induced immunity, particularly concerning Fc-mediated effector functions. This knowledge is pivotal in guiding the design of optimal vaccination strategies against malaria, informing decision making for future endeavors in this critical field.
疫苗是预防传染病的高效工具，在抗击疟疾的斗争中也被视为必不可少。疫苗诱导的免疫通常由抗体介导。我们最近开展了一项针对SumayaVac-1的首次人体临床试验，SumayaVac-1是一种基于重组全长裂殖子表面蛋白1（MSP1）并以GLA-SE作为佐剂配制的疟疾疫苗。接种MSP1是安全的，并且能引发可持续的IgG抗体滴度，该滴度超过了在非洲半免疫人群中观察到的水平。此外，IgG抗体刺激了各种与疟疾防护相关的Fc介导的效应机制。然而，这些功能逐渐减弱。在这里，我们表明SumayaVac-1的最初两剂主要诱导了嗜细胞亚类IgG1和IgG3。出乎意料的是，在第三次和第四次接种后，IgG亚类组成发生了变化。具体而言，逐渐向IgG4抗体转变，IgG4抗体参与Fc介导的效应功能的能力降低，并且亲和力增加。总之，我们对MSP1疫苗接种抗体反应的分析揭示了向非炎性IgG4抗体的时间性转变。这些发现强调了考虑IgG亚类组成对疫苗诱导免疫的影响的重要性，特别是关于Fc介导的效应功能。这些知识对于指导针对疟疾的最佳疫苗接种策略设计、为这一关键领域的未来努力提供决策依据至关重要。
