Safety and immunogenicity of a recombinant multivalent group A streptococcal vaccine in healthy adults - Phase 1 trial
Safety and immunogenicity of a recombinant multivalent group A streptococcal vaccine in healthy adults - Phase 1 trial
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DOI：
10.1001/jama.292.6.709
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发表时间：
2004-08-11
影响因子：
120.7
通讯作者：
Dale, JB
中科院分区：
文献类型：
--
作者：
Kotloff, KL;Corretti, M;Dale, JB
A组链球菌感染及其后遗症是一个全球性的健康问题。目的初步评价含有1、3、5、6、19和24型N端M蛋白片段的重组A群链球菌融合肽疫苗在健康志愿者中的安全性和免疫原性。在1999年10月5日至2003年2月26日期间，使用报纸广告和张贴的传单，从马里兰州的巴尔的摩大都会地区招募了28名年龄在18至50岁之间的健康成年志愿者，每名志愿者接受3次间隔的肌内注射，将50 μ g（n=8）、100 μ g（n=10）或200 μ g（n=10）的六价A组链球菌疫苗与氢氧化铝一起配制到交替臂的三角肌中。主要结果测量临床安全性的评估，包括与宿主组织交叉反应的抗体的激发，和免疫原性测定的酶联免疫吸附试验（ELISA）和测定的调理吞噬细胞和杀真菌抗体responses.Results一年的密集随访显示，疫苗是耐受性良好。没有证据表明存在组织交叉反应抗体或免疫并发症。在最高（200 μ g）剂量下，通过ELISA检测，接种疫苗引起针对所有6种组分M抗原的几何平均抗体水平显著增加（所有P
Context Group A streptococcal infections and their sequelae represent a global health problem. Recent advances have allowed previous obstacles associated with group A streptococcal vaccine development to be overcome.Objective To preliminarily evaluate the safety and immunogenicity of ascending doses of a recombinant fusion peptide group A streptococcal vaccine containing N-terminal M protein fragments from serotypes 1, 3, 5, 6, 19, and 24 in healthy volunteers.Design, Setting, and Participants An open-label, uncontrolled, dose-ascending phase 1 vaccine trial of 28 healthy adult volunteers aged 18 to 50 years recruited from the metropolitan area of Baltimore, Md, between October 5, 1999, and February 26, 2003, using newspaper advertisements and posted fliers, and evaluated in the outpatient facility of the Center for Vaccine Development.Interventions Each volunteer received 3 spaced intramuscular injections of 50 mug (n=8), 100 mug (n=10), or 200 mug (n=10) of hexavalent group A streptococcal vaccine formulated with aluminum hydroxide into the deltoid muscle of alternating arms.Main Outcome Measures Assessments of clinical safety, including elicitation of antibodies that cross-react with host tissues, and immunogenicity as measured by enzyme-linked immunosorbent assay (ELISA) and assays of opsonophagocytic- and bactericidal-antibody responses.Results One year of intensive follow-up revealed the vaccine to be well tolerated. There was no evidence of tissue cross-reactive antibodies or immunological complications. At the highest (200 mug) dose, vaccination elicited significant increases in geometric mean antibody levels to all 6 component M antigens by ELISA (all P