Katial Rohit K, Brandt Brenda L, Moran Ellen E, Marks Stephen, Agnello Victor, Zollinger Wendell D
Walter Reed Army Medical Center, Washington, DC 20307, USA.
Infect Immun. 2002 Feb;70(2):702-7. doi: 10.1128/IAI.70.2.702-707.2002.
The presently licensed meningococcal vaccine is a tetravalent capsular polysaccharide vaccine that induces immunity to serogroups A, C, Y, and W-135 but not to group B, which causes nearly half of the meningitis cases in the United States. The purpose of this study was to evaluate the safety and immunogenicity of an intranasal native outer membrane vesicle (NOMV) vaccine prepared from a capsule negative strain of group B of Neisseria meningitidis. In this study all volunteers received the same dose of vaccine, but we evaluated two different immunization schedules and the oropharyngeal and intranasal routes of vaccine delivery, assessed nasal cytology for cellular infiltration, and measured antibody-secreting cells (enzyme-linked immunospot assay [ELISPOT]) as an early marker for systemic immune response. Additionally, both intranasal and serum vaccine-specific antibodies were measured as well as serum bactericidal activity. Four groups with a total of 42 subjects were immunized on days 0, 28, and 56. Group 3 received an additional dose on day 7. Group 2 subjects were immunized both intranasally and oropharyngeally. Group 4 received a different lot of vaccine. All groups received approximately 1,200 microg of vaccine per subject. Patients were evaluated for side effects. The vaccine was well tolerated without evidence of inflammation on nasal cytology. The group receiving the extra vaccine dose showed the maximum increase in bactericidal activity. Thirty of 42 subjects demonstrated an increase in meningococcus-specific intranasal immunoglobulin A (IgA) titers, while 23 of 42 demonstrated an increase in specific IgG titers. The group receiving vaccine intranasally and oropharyngeally showed the highest rise in intranasal titers for both IgA and IgG. Groups 1, 3, and 4 showed a significant increase in antibody-secreting cells on ELISPOT. Eighteen of 42 volunteers demonstrated a fourfold or greater rise in bactericidal titers, with 81% showing an increase over baseline. We have demonstrated the immunogenicity and safety of a group B lipopolysaccharide-containing, intranasal, NOMV vaccine.
目前已获许可的脑膜炎球菌疫苗是一种四价荚膜多糖疫苗，可诱导对A、C、Y和W - 135血清群的免疫，但对B群无免疫效果，而B群在美国导致了近一半的脑膜炎病例。本研究的目的是评估由脑膜炎奈瑟菌B群的无荚膜菌株制备的鼻内天然外膜囊泡（NOMV）疫苗的安全性和免疫原性。在本研究中，所有志愿者均接受相同剂量的疫苗，但我们评估了两种不同的免疫接种方案以及疫苗接种的口咽和鼻内途径，评估鼻细胞学检查细胞浸润情况，并测量抗体分泌细胞（酶联免疫斑点测定[ELISPOT]）作为全身免疫反应的早期标志物。此外，还测量了鼻内和血清中疫苗特异性抗体以及血清杀菌活性。四组共42名受试者在第0、28和56天进行免疫接种。第3组在第7天额外接种一剂。第2组受试者通过鼻内和口咽途径进行免疫接种。第4组接种不同批次的疫苗。所有组每名受试者均接受约1200微克疫苗。对患者进行副作用评估。疫苗耐受性良好，鼻细胞学检查未发现炎症迹象。接受额外疫苗剂量的组杀菌活性增加最多。42名受试者中有30名鼻内脑膜炎球菌特异性免疫球蛋白A（IgA）滴度升高，42名中有23名特异性IgG滴度升高。通过鼻内和口咽途径接种疫苗的组鼻内IgA和IgG滴度升高幅度最大。第1、3和4组在ELISPOT上抗体分泌细胞显著增加。42名志愿者中有18名杀菌滴度升高四倍或更高，81%的志愿者杀菌滴度高于基线水平。我们已经证明了含B群脂多糖的鼻内NOMV疫苗的免疫原性和安全性。
