Moderna, Inc., 325 Binney St., Cambridge, MA 02142, USA.
Department of Medicine, University of Tennessee Health Science Center, 956 Court Ave., Memphis, TN 38163, USA.
Vaccine. 2024 Sep 17;42(22):126205. doi: 10.1016/j.vaccine.2024.126205. Epub 2024 Aug 13.
Group A Streptococcus (Strep A) causes both uncomplicated and severe invasive infections, as well as the post-infection complications acute rheumatic fever and rheumatic heart disease. Despite the high global burden of disease resulting from Strep A infections, there is not a licensed vaccine. A 30-valent M protein-based vaccine has previously been shown to be immunogenic in animal models and in a Phase I clinical trial (NCT02564237). Here, we assessed the immunogenicity of a 30-valent messenger (m)RNA vaccine designed to express the same M peptide targets as the 30-valent protein vaccine and compared it with the protein vaccine.
Female New Zealand white rabbits were immunized with one of four vaccine formulations (3 doses of each formulation at days 1, 28, and 56): soluble mRNA (100 μg/animal), C-terminal transmembrane mRNA (100 μg/animal), protein vaccine (400 μg/animal), or a non-translatable RNA control (100 μg/animal). Serum was collected one day prior to the first dose and on days 42 and 70. Rabbit serum samples were assayed for antibody levels against synthetic M peptides by ELISA. HL-60 opsonophagocytic killing (OPK) assays were performed to assess functional antibody levels.
Serum IgG levels were similar for the mRNA and protein vaccines. The CtTM version of the mRNA vaccine elicited slightly higher antibody levels than the mRNA designed to express soluble proteins. OPK activity was similar for the mRNA and protein vaccines, regardless of M type.
The total antibody responses and functional antibody levels elicited by the 30-valent mRNA Strep A vaccines were similar to those observed following immunization with the analogous protein vaccine. The mRNA vaccine platform provides potential advantages to protein-based vaccines including inherent adjuvant activity, increased production efficiency, lower cost, and the potential to rapidly change epitopes/peptides, all of which are important considerations related to multivalent Strep A vaccine development.
A 组链球菌（Strep A）可引起非复杂性和严重侵袭性感染，以及感染后并发症急性风湿热和风湿性心脏病。尽管 A 组链球菌感染导致的全球疾病负担很高，但目前还没有获得许可的疫苗。先前的动物模型和 I 期临床试验（NCT02564237）表明，一种 30 价 M 蛋白为基础的疫苗具有免疫原性。在这里，我们评估了一种 30 价信使（m）RNA 疫苗的免疫原性，该疫苗旨在表达与 30 价蛋白疫苗相同的 M 肽靶标，并将其与蛋白疫苗进行了比较。
雌性新西兰白兔用四种疫苗制剂之一（每种制剂 3 剂，在第 1、28 和 56 天）进行免疫：可溶性 mRNA（100μg/动物）、C 端跨膜 mRNA（100μg/动物）、蛋白疫苗（400μg/动物）或非翻译 RNA 对照（100μg/动物）。在第一剂前一天和第 42 天和第 70 天采集血清。通过 ELISA 检测兔血清样品针对合成 M 肽的抗体水平。进行 HL-60 调理吞噬杀伤（OPK）试验以评估功能性抗体水平。
mRNA 和蛋白疫苗的血清 IgG 水平相似。CtTM 版本的 mRNA 疫苗比设计表达可溶性蛋白的 mRNA 疫苗稍微引起更高的抗体水平。无论 M 型如何，mRNA 和蛋白疫苗的 OPK 活性均相似。
30 价 mRNA Strep A 疫苗引起的总抗体反应和功能性抗体水平与免疫接种类似蛋白疫苗后观察到的反应相似。mRNA 疫苗平台为基于蛋白的疫苗提供了潜在优势，包括固有佐剂活性、提高生产效率、降低成本和快速改变表位/肽的潜力，所有这些都是与多价 Strep A 疫苗开发相关的重要考虑因素。
