Institute for Glycomics, Griffith University, Queensland, 4222, Australia.
Sci Rep. 2017 Oct 23;7(1):13786. doi: 10.1038/s41598-017-14157-7.
Globally, group A streptococcal infections are responsible for over 500,000 deaths per year. A safe vaccine that does not induce autoimmune pathology and that affords coverage for most GAS serotypes is highly desired. We have previously demonstrated that a vaccine based on the conserved M-protein epitope, J8 was safe and immunogenic in a pilot Phase I study. We subsequently improved vaccine efficacy by incorporation of a B-cell epitope from the IL-8 protease, SpyCEP, which protected IL-8 and enhanced neutrophil ingress to the site of infection. We have now substituted the carrier protein, diphtheria toxoid with its superior analogue, CRM197 which provides better immunogenicity and is widely used in licenced human vaccines. The new vaccine was compared with the DT conjugate vaccine to confirm that these modifications have not altered the physicochemical properties of the vaccine. This vaccine, when tested in an animal model of GAS infection, demonstrated significant reduction in systemic and local GAS burden, with comparable efficacy to the DT conjugate vaccine. The vaccine was shown to be equally effective in the presence of human plasma and in the presence of pre-existing DT-specific antibodies, thus minimising concerns regarding its potential efficacy in humans.
在全球范围内，A 组链球菌感染每年导致超过 50 万人死亡。人们非常希望有一种安全的疫苗，它不会引起自身免疫性疾病，并能覆盖大多数 GAS 血清型。我们之前已经证明，基于保守 M 蛋白表位 J8 的疫苗在一项 I 期试验中是安全和免疫原性的。随后，我们通过加入来自白细胞介素-8 蛋白酶 SpyCEP 的 B 细胞表位来提高疫苗的疗效，SpyCEP 可以保护白细胞介素-8 并增强中性粒细胞进入感染部位。我们现在已经用其优越的类似物 CRM197 代替了载体蛋白白喉类毒素，CRM197 提供了更好的免疫原性，并广泛用于许可的人类疫苗中。新疫苗与 DT 缀合疫苗进行了比较，以确认这些修饰没有改变疫苗的理化性质。在 GAS 感染的动物模型中测试时，这种疫苗显示出对全身和局部 GAS 负担的显著减少，与 DT 缀合疫苗的疗效相当。该疫苗在存在人血浆和存在预先存在的 DT 特异性抗体的情况下同样有效，从而最大限度地减少了人们对其在人类中潜在疗效的担忧。
