Pollard A J, Galassini R, Rouppe van der Voort E M, Hibberd M, Booy R, Langford P, Nadel S, Ison C, Kroll J S, Poolman J, Levin M
Departments of Paediatrics and Infectious Diseases & Microbiology, Imperial College School of Medicine, St. Mary's Hospital, London W2 1PG, United Kingdom.
Infect Immun. 1999 May;67(5):2452-63. doi: 10.1128/IAI.67.5.2452-2463.1999.
There is an urgent need for effective vaccines against serogroup B Neisseria meningitidis. Current experimental vaccines based on the outer membrane proteins (OMPs) of this organism provide a measure of protection in older children but have been ineffective in infants. We postulated that the inability of OMP vaccines to protect infants might be due to age-dependent defects in cellular immunity. We measured proliferation and in vitro production of gamma interferon (IFN-gamma), tumor necrosis factor alpha, and interleukin-10 (IL-10) in response to meningococcal antigens by peripheral blood mononuclear cells (PBMCs) from children convalescing from meningococcal disease and from controls. After meningococcal infection, the balance of cytokine production by PBMCs from the youngest children was skewed towards a TH1 response (low IL-10/IFN-gamma ratio), while older children produced more TH2 cytokine (higher IL-10/IFN-gamma ratio). There was a trend to higher proliferative responses by PBMCs from older children. These responses were not influenced by the presence or subtype of class 1 (PorA) OMP or by the presence of class 2/3 (PorB) or class 4 OMP. Even young infants might be expected to develop adequate cellular immune responses to serogroup B N. meningitidis vaccines if a vaccine preparation can be formulated to mimic the immune stimulus of invasive disease, which may include stimulation of TH2 cytokine production.
迫切需要针对B群脑膜炎奈瑟菌的有效疫苗。目前基于该生物体外膜蛋白（OMP）的实验性疫苗在大龄儿童中提供了一定程度的保护，但对婴儿无效。我们推测OMP疫苗无法保护婴儿可能是由于细胞免疫中与年龄相关的缺陷。我们检测了正在从脑膜炎球菌病康复的儿童和对照组儿童外周血单核细胞（PBMC）对脑膜炎球菌抗原的增殖反应以及γ干扰素（IFN-γ）、肿瘤坏死因子α和白细胞介素-10（IL-10）的体外产生情况。脑膜炎球菌感染后，最小儿童的PBMC产生的细胞因子平衡偏向TH1反应（低IL-10/IFN-γ比值），而大龄儿童产生更多的TH2细胞因子（更高的IL-10/IFN-γ比值）。大龄儿童的PBMC有更高增殖反应的趋势。这些反应不受1类（PorA）OMP的存在或亚型、2/3类（PorB）或4类OMP的存在影响。如果能够配制一种疫苗制剂来模拟侵袭性疾病的免疫刺激，包括刺激TH2细胞因子的产生，那么即使是幼儿也有望对B群脑膜炎奈瑟菌疫苗产生足够的细胞免疫反应。
