Amin Mohammed N, Sinclair James E, Curtis Brittany, Sycheva Lada, Fox Heather, Choi Myeong-Jin, Shridhar Surekha, Kolasny Jacqueline, Nkeze Joseph, Apolinario Ethel, Hyun Sang, Hegerle Nicolas, Sen Shaichi, Permala Booth Jasnehta, Leney Mark, Molrine Deborah, Saia Greg, Pasetti Marcela, Broering Teresa, Michon Francis, Malley Richard, Siber George R, Tennant Sharon M, Ambrosino Donna, Simon Raphael, Cross Alan
Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Affinivax Inc. (a GSK company), Cambridge, Massachusetts, USA.
mBio. 2025 Jun 26:e0080725. doi: 10.1128/mbio.00807-25.
(KP) and (PA) are leading causes of healthcare-associated and community-acquired infections. Despite decades of efforts, there are no licensed vaccines for either pathogen. The surface O polysaccharides (OPS) of and are essential virulence factors for these bacteria and are targets of protective antibacterial antibodies. The multiple antigen presenting system (MAPS) vaccine platform was used to create a multivalent / vaccine in which the surface OPS of four and eight strains were linked to a high MW biotinylated (KO) K19 capsular polysaccharide backbone and subsequently linked to pathogen-specific fusion proteins, consisting of MrkA, the flagellin B D2 subunit, and PcrV. We show here that these MAPS complexes incorporating KP and PA OPS, as well as pathogen-specific proteins, were highly immunogenic in rabbits and mice and induced functionally active antibodies and in murine animal models.IMPORTANCEInfections caused by (KP) and (PA) are widely recognized to be of "urgent" and "serious" concern, in part because of their widespread antimicrobial resistance. To date, there is no licensed vaccine for either pathogen. We developed a novel multiple antigen presenting system (MAPS) vaccine platform that contains eight O polysaccharides (OPS) of PA and four OPS of KP, which will cover over 80% of clinical infections with these pathogens. In addition, this vaccine includes three pathogen-relevant proteins acting both as carrier proteins to provide T cell help for these polysaccharides as well as to elicit functionally active antibodies that may also protect against KP and PA infection. The use of pathogen-relevant proteins that may contribute to vaccine efficacy in place of the more traditional carrier proteins is a novel concept. The MAPS vaccine platform also generates Th17 and Th1 responses. This KP/PA MAPS vaccine may prevent infection with these pathogens and reduce their transmissibility.
肺炎克雷伯菌（KP）和铜绿假单胞菌（PA）是医疗保健相关感染和社区获得性感染的主要原因。尽管经过数十年的努力，但针对这两种病原体均无获批疫苗。KP和PA的表面O多糖（OPS）是这些细菌的重要毒力因子，也是保护性抗菌抗体的靶点。多抗原呈递系统（MAPS）疫苗平台被用于制备一种多价KP/PA疫苗，其中四种KP菌株和八种PA菌株的表面OPS与高分子量生物素化的大肠杆菌（KO）K19荚膜多糖主链相连，随后与病原体特异性融合蛋白相连，这些融合蛋白由MrkA、PA鞭毛蛋白B D2亚基和PcrV组成。我们在此表明，这些包含KP和PA OPS以及病原体特异性蛋白的MAPS复合物在兔和小鼠中具有高度免疫原性，并在鼠类动物模型中诱导产生了功能活性抗体。重要性肺炎克雷伯菌（KP）和铜绿假单胞菌（PA）引起的感染被广泛认为是“紧急”和“严重”问题，部分原因是它们广泛的抗菌耐药性。迄今为止，针对这两种病原体均无获批疫苗。我们开发了一种新型多抗原呈递系统（MAPS）疫苗平台，其包含PA的八种O多糖（OPS）和KP的四种OPS，可覆盖这些病原体超过80%的临床感染。此外，这种疫苗包括三种与病原体相关的蛋白，它们既作为载体蛋白为这些多糖提供T细胞辅助，又能引发可能也对KP和PA感染具有保护作用的功能活性抗体。使用可能有助于疫苗效力的与病原体相关蛋白来替代更传统的载体蛋白是一个新概念。MAPS疫苗平台还能产生Th17和Th1反应。这种KP/PA MAPS疫苗可能预防这些病原体的感染并降低其传播性。
