Harbison-Price Nichaela, Sebina Ismail, Bolton Rhiannon A, Finn Meredith, Cork Amanda J, Courtney Isabel G, Hancock Steven, Pelingon Ruby, Richter Johanna, Ericsson Olivia, Green Shannon, Cuellar Celeste, Davis Laura, Pullinger Brody, Na Jack, Elangovan Gayathiri, De Oliveira David M P, Curren Bodie F, Bickham Nia, Aguirre Miguel, Dold Christina, Brouwer Stephan, Plante Obadiah, Belz Gabrielle T, Walker Mark J
Centre for Superbug Solutions, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia.
Frazer Institute, The University of Queensland, Brisbane, QLD, Australia.
Nat Commun. 2025 Jul 1;16(1):5439. doi: 10.1038/s41467-025-60580-0.
A commercial vaccine to address the high global burden of Group A Streptococcus (GAS) disease is an urgent and unmet medical need. Messenger RNA (mRNA) lipid-nanoparticle (LNP) vaccines represent a largely untapped platform for targeting bacterial pathogens. Here, we evaluate the immunogenicity and preclinical efficacy of a multicomponent mRNA-LNP vaccine formulation based on the GAS vaccine, Combo#5. Combo#5 mRNA-LNP antigens confer protection from infection in mouse intraperitoneal and subcutaneous challenge models. Combo#5 mRNA-LNP vaccination generates significantly increased frequencies and numbers of effector type CD4+ and CD8 + T cells in the spleen, enhances T follicular helper cells, germinal center B cells and memory B cells in the spleen and draining lymph nodes, and boosts the production of antigen-specific antibodies. These findings demonstrate the potential of the mRNA-LNP platform for the development of vaccines against bacterial pathogens.
一种应对全球A群链球菌（GAS）疾病高负担的商用疫苗是一项紧迫且未得到满足的医学需求。信使核糖核酸（mRNA）脂质纳米颗粒（LNP）疫苗是一种在很大程度上尚未开发的针对细菌病原体的平台。在此，我们评估了基于GAS疫苗Combo#5的多组分mRNA-LNP疫苗制剂的免疫原性和临床前疗效。Combo#5 mRNA-LNP抗原在小鼠腹腔和皮下攻击模型中可提供感染保护。Combo#5 mRNA-LNP疫苗接种显著增加了脾脏中效应型CD4+和CD8+ T细胞的频率和数量，增强了脾脏和引流淋巴结中的T滤泡辅助细胞、生发中心B细胞和记忆B细胞，并促进了抗原特异性抗体的产生。这些发现证明了mRNA-LNP平台在开发针对细菌病原体疫苗方面的潜力。
