Marsay L, Dold C, Green C A, Rollier C S, Norheim G, Sadarangani M, Shanyinde M, Brehony C, Thompson A J, Sanders H, Chan H, Haworth K, Derrick J P, Feavers I M, Maiden M C, Pollard A J
Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Centre, CCVTM, Churchill Lane, Oxford OX37LE, United Kingdom.
Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Centre, CCVTM, Churchill Lane, Oxford OX37LE, United Kingdom.
J Infect. 2015 Sep;71(3):326-37. doi: 10.1016/j.jinf.2015.05.006. Epub 2015 May 15.
Outer membrane vesicle (OMV) vaccines are used against outbreaks of capsular group B Neisseria meningitidis (MenB) caused by strains expressing particular PorA outer membrane proteins (OMPs). Ferric enterobactin receptor (FetA) is another variable OMP that induces type-specific bactericidal antibodies, and the combination of judiciously chosen PorA and FetA variants in vaccine formulations is a potential approach to broaden protection of such vaccines.
The OMV vaccine MenPF-1 was generated by genetically modifying N. meningitidis strain 44/76 to constitutively express FetA. Three doses of 25 μg or 50 μg of MenPF-1 were delivered intra-muscularly to 52 healthy adults.
MenPF-1 was safe and well tolerated. Immunogenicity was measured by serum bactericidal assay (SBA) against wild-type and isogenic mutant strains. After 3 doses, the proportion of volunteers with SBA titres ≥1:4 (the putative protective titre) was 98% for the wild-type strain, and 77% for the strain 44/76 FetA(on)PorA(off) compared to 51% in the strain 44/76 FetA(off)PorA(off), demonstrating that vaccination with MenPF-1 simultaneously induced FetA and PorA bactericidal antibodies.
This study provides a proof-of-concept for generating bactericidal antibodies against FetA after OMV vaccination in humans. Prevalence-based choice of PorA and FetA types can be used to formulate a vaccine for broad protection against MenB disease.
外膜囊泡（OMV）疫苗用于预防由表达特定PorA外膜蛋白（OMP）的菌株引起的B群脑膜炎奈瑟菌（MenB）暴发。铁肠杆菌素受体（FetA）是另一种可变的OMP，可诱导型特异性杀菌抗体，在疫苗配方中明智地选择PorA和FetA变体的组合是扩大此类疫苗保护范围的一种潜在方法。
通过对脑膜炎奈瑟菌菌株44/76进行基因改造以组成性表达FetA，制备了OMV疫苗MenPF-1。将三剂25μg或50μg的MenPF-1肌肉注射给52名健康成年人。
MenPF-1安全且耐受性良好。通过针对野生型和同基因突变菌株的血清杀菌试验（SBA）测量免疫原性。三剂接种后，野生型菌株的SBA滴度≥1:4（假定的保护滴度）的志愿者比例为98%，44/76 FetA（开启）PorA（关闭）菌株为77%，而44/76 FetA（关闭）PorA（关闭）菌株为51%，这表明接种MenPF-1同时诱导了FetA和PorA杀菌抗体。
本研究为人类接种OMV疫苗后产生针对FetA的杀菌抗体提供了概念验证。基于流行率选择PorA和FetA类型可用于配制一种疫苗，以广泛预防MenB疾病。
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