Dold Christina, Oguti Blanché, Silva-Reyes Laura, Stanzelova Anna, Raymond Meriel, Smith Catherine C, Moore Maria, Barton Anna, Choi Edward M, Plested Emma, Tanha Kiarash, Louth Jennifer, Holland Ann, Cook Robert, King Jessica, Lucidarme Jay, Borrow Ray, Hill Adrian V S, Beernink Peter T, Liu Xinxue, Pollard Andrew J, Rollier Christine S
Oxford Vaccine Group, Department of Paediatrics, University of Oxford and NIHR Oxford Biomedical Research Centre, CCVTM, Churchill Lane, Oxford OX37LE, UK.
Division of Infection and Immunity, Faculty of Medical Sciences, University College London, London WC1E 6JF, UK.
Sci Transl Med. 2025 May 7;17(797):eadn1441. doi: 10.1126/scitranslmed.adn1441.
Capsular group B meningococcus (MenB) remains an important cause of disease globally, and additional vaccines against MenB would aid in reducing the incidence of infection. Previous work has demonstrated that a MenB adenoviral-vectored vaccine, ChAdOx1 MenB.1, elicited high serum bactericidal responses in preclinical models after a single dose, supporting further clinical development of this vaccine. Here, we report the results of a trial designed to assess the safety and immunogenicity of ChAdOx1 MenB.1 in healthy adults aged 18 to 50. In this phase 1/2a, single-center trial, participants received one or two doses of ChAdOx1 MenB.1 at days 0 and 180. One dose of ChAdOx1 MenB.1 was also given at day 180 to some individuals primed with one dose of 4CMenB at day 0. Participants recorded their symptoms in an electronic diary after vaccination, and safety blood readouts were monitored. Serum bactericidal antibody (SBA) assays were performed against a panel of MenB target strains. ChAdOx1 MenB.1 was well tolerated with no safety concerns and elicited protective SBA titers against a MenB strain expressing a homologous factor H-binding protein (fHbp) variant in 100% of participants after two doses. However, cross-reactivity analysis indicated a low SBA response to strains expressing heterologous fHbp, suggesting that a multivalent vaccine may be needed. In sum, ChAdOx1 MenB.1 is immunogenic in humans, and addition of another fHbp variant or of another antigen in this platform could provide an approach to extend protection against endemic MenB disease.
B群脑膜炎球菌（MenB）仍是全球疾病的一个重要病因，研发更多针对MenB的疫苗将有助于降低感染发病率。此前的研究表明，一种MenB腺病毒载体疫苗ChAdOx1 MenB.1在临床前模型中单次给药后能引发高血清杀菌反应，支持该疫苗进一步开展临床研究。在此，我们报告一项旨在评估ChAdOx1 MenB.1在18至50岁健康成年人中的安全性和免疫原性的试验结果。在这项1/2a期单中心试验中，参与者在第0天和第180天接受一剂或两剂ChAdOx1 MenB.1。部分在第0天接种一剂4CMenB进行 priming的个体在第180天也接种一剂ChAdOx1 MenB.1。参与者在接种疫苗后通过电子日记记录症状，并监测安全性血液指标。针对一组MenB目标菌株进行血清杀菌抗体（SBA）检测。ChAdOx1 MenB.1耐受性良好，无安全性问题，两剂接种后100%的参与者针对表达同源因子H结合蛋白（fHbp）变体的MenB菌株产生了保护性SBA滴度。然而，交叉反应性分析表明，对表达异源fHbp的菌株的SBA反应较低，这表明可能需要一种多价疫苗。总之，ChAdOx1 MenB.1在人体中具有免疫原性，在该平台中添加另一种fHbp变体或另一种抗原可能为扩大针对地方性MenB疾病的保护提供一种方法。
