Malfertheiner Peter, Schultze Viola, Rosenkranz Bernd, Kaufmann Stefan H E, Ulrichs Timo, Novicki Deborah, Norelli Francesco, Contorni Mario, Peppoloni Samuele, Berti Duccio, Tornese Daniela, Ganju Jitendra, Palla Emanuela, Rappuoli Rino, Scharschmidt Bruce F, Del Giudice Giuseppe
Otto-von-Guericke Universitaet, Department of Gastroenterology, Hepatology and Infectious Diseases, Magdeburg, Germany.
Gastroenterology. 2008 Sep;135(3):787-95. doi: 10.1053/j.gastro.2008.05.054. Epub 2008 May 28.
Helicobacter pylori infection is among the most common human infections and the major risk factor for peptic disease and gastric cancer. Immunization with vaccines containing the H pylori vacuolating cytotoxin A (VacA), cytotoxin-associated antigen (CagA), and neutrophil-activating protein (NAP), alone or in combination, have been shown to prevent experimental infection in animals.
We sought to study the safety and immunogenicity of a vaccine consisting of recombinant VacA, CagA, and NAP given intramuscularly with aluminium hydroxide as an adjuvant to noninfected healthy subjects.
This controlled, single-blind Phase I study randomized 57 H pylori-negative volunteers into 7 study arms exploring 2 dosages (10 and 25 microg) of each antigen and 3 schedules (0, 1, 2 weeks; 0, 1, 2 months; and 0, 1, 4 months) versus alum controls. All participants were followed for 5 months. Thirty-six subjects received a booster vaccination 18-24 months after the completion of the primary vaccination.
Local and systemic adverse reactions were mild and similar in placebo and vaccine recipients on the monthly schedules. All subjects responded to 1 or 2 of the antigens and 86% of all vaccines mounted immunoglobulin G antibody responses to all 3 antigens. Vaccinees exhibited an antigen-specific cellular response. Vaccination 18-24 months later elicited anamnestic antibody and cellular responses.
This intramuscular H pylori vaccine demonstrated satisfactory safety and immunogenicity, produced antigen-specific T-cell memory, and, therefore, warrants further clinical study.
幽门螺杆菌感染是最常见的人类感染之一，也是消化性疾病和胃癌的主要危险因素。单独或联合使用含幽门螺杆菌空泡毒素A（VacA）、细胞毒素相关抗原（CagA）和中性粒细胞激活蛋白（NAP）的疫苗进行免疫接种，已被证明可预防动物实验性感染。
我们试图研究一种由重组VacA、CagA和NAP组成的疫苗，以氢氧化铝作为佐剂，对未感染的健康受试者进行肌肉注射的安全性和免疫原性。
这项对照、单盲的I期研究将57名幽门螺杆菌阴性志愿者随机分为7个研究组，探索每种抗原的2种剂量（10和25微克）和3种接种方案（0、1、2周；0、1、2个月；以及0、1、4个月），并与明矾对照组进行比较。所有参与者随访5个月。36名受试者在初次接种完成后18 - 24个月接受加强接种。
按月接种方案，安慰剂组和疫苗接种组的局部和全身不良反应均较轻且相似。所有受试者对1种或2种抗原产生反应，所有疫苗中有86%对所有3种抗原产生免疫球蛋白G抗体反应。接种疫苗者表现出抗原特异性细胞反应。18 - 24个月后接种疫苗引发了回忆性抗体和细胞反应。
这种肌肉注射的幽门螺杆菌疫苗显示出令人满意的安全性和免疫原性，产生了抗原特异性T细胞记忆，因此值得进一步进行临床研究。
