Abou-Zeid C, Gares M P, Inwald J, Janssen R, Zhang Y, Young D B, Hetzel C, Lamb J R, Baldwin S L, Orme I M, Yeremeev V, Nikonenko B V, Apt A S
Department of Medical Microbiology, Imperial College School of Medicine at St. Mary's, London, United Kingdom.
Infect Immun. 1997 May;65(5):1856-62. doi: 10.1128/iai.65.5.1856-1862.1997.
A 19-kDa lipoprotein from Mycobacterium tuberculosis was expressed as a recombinant antigen in the nonpathogenic mycobacterial host strain M. vaccae. Immunization of mice with the recombinant M. vaccae resulted in induction of a strong type 1 immune response to the 19-kDa antigen, characterized by immunoglobulin G2a (IgG2a) antibodies and gamma interferon (IFN-gamma) production by splenocytes. Immunization with the same antigen in incomplete Freund's adjuvant induced a strong IgG1 response with only low levels of IFN-gamma. Subsequent intravenous and aerosol challenges of immunized mice with virulent M. tuberculosis demonstrated no evidence of protection associated with the response to the 19-kDa antigen; in fact, the presence of the recombinant 19-kDa antigen abrogated the limited protection conferred by M. vaccae (vector control). The recombinant M. vaccae system is a convenient approach to induction of type 1 responses to M. tuberculosis antigens. However, the unexpected reduction in protective efficacy of M. vaccae expressing the 19-kDa antigen highlights the complexity of testing recombinant subunit vaccines and the need for a better understanding of the immune mechanisms required for effective vaccination against tuberculosis.
结核分枝杆菌的一种19 kDa脂蛋白在非致病性分枝杆菌宿主菌株母牛分枝杆菌中作为重组抗原表达。用重组母牛分枝杆菌免疫小鼠可诱导对19 kDa抗原产生强烈的1型免疫反应，其特征为免疫球蛋白G2a（IgG2a）抗体以及脾细胞产生γ干扰素（IFN-γ）。在不完全弗氏佐剂中用相同抗原免疫诱导出强烈的IgG1反应，仅产生低水平的IFN-γ。随后用强毒力结核分枝杆菌对免疫小鼠进行静脉内和气溶胶攻击，未显示出与对19 kDa抗原的反应相关的保护证据；事实上，重组19 kDa抗原的存在消除了母牛分枝杆菌（载体对照）所提供的有限保护。重组母牛分枝杆菌系统是诱导对结核分枝杆菌抗原产生1型反应的便捷方法。然而，表达19 kDa抗原的母牛分枝杆菌保护效力意外降低，凸显了测试重组亚单位疫苗的复杂性以及更好地理解有效抗结核疫苗接种所需免疫机制的必要性。
