SALK J E, LAURENT A M
J Exp Med. 1952 May 1;95(5):429-47. doi: 10.1084/jem.95.5.429.
Untoward reactions at the site of inoculation were not observed in monkeys vaccinated with influenza virus incorporated in a water-in-oil emulsion without acid-fast bacilli. Studies were then made to measure some of the dimensions of antigenicity of these emulsions to evaluate the extent of the immunologic adjuvant effect. This included measurements of height and persistence of the antibody response to inoculation and measurements of the extent to which the vaccine could be diluted and still induce antibody formation; i.e., antigenic extinction. In addition, comparisons were made of the rates of development of hemagglutination-inhibiting, virus-neutralizing, and complement-fixing antibody activities to determine the relationship among these three properties of the serum of immunized animals. It was found that levels of antibody many fold higher were induced by the virus-adjuvant mixtures as compared with virus in an aqueous menstruum, and that the level of antibody induced was related to the quantity of antigen incorporated in the emulsion. The stock vaccine when emulsified could be diluted 100,000-fold and was still active in antibody formation whereas a 100-fold dilution of the antigen without emulsification was essentially ineffective. Equivalent quantities of virus in 0.1 ml. or 1.0 ml. of emulsion induced antibody responses that were indistinguishable with respect to level or persistence. In comparing the course of antibody development it was found that hemagglutination-inhibiting, virus-neutralizing, and complement-fixing antibodies develop at different rates; careful analysis of the data derived from the present study together with other observations warrant the conclusion that these antibody activities are not present in constant proportion and are independent of one another. The implications of this observation and of the others mentioned above are discussed.
在用不含抗酸杆菌的油包水乳剂包裹的流感病毒对猴子进行接种时,未观察到接种部位出现不良反应。随后进行了一些研究,以测量这些乳剂的某些抗原性维度,从而评估免疫佐剂效应的程度。这包括对接种后抗体反应的高度和持久性的测量,以及对疫苗可稀释程度且仍能诱导抗体形成的程度的测量,即抗原消退。此外,还比较了血凝抑制、病毒中和及补体结合抗体活性的发展速率,以确定免疫动物血清的这三种特性之间的关系。结果发现,与水相介质中的病毒相比,病毒 - 佐剂混合物诱导的抗体水平高出许多倍,且诱导的抗体水平与乳剂中所含抗原的量有关。乳化后的库存疫苗可稀释100,000倍,且在抗体形成方面仍具有活性,而未乳化的抗原稀释100倍基本上无效。0.1毫升或1.0毫升乳剂中等量的病毒诱导的抗体反应在水平或持久性方面没有差异。在比较抗体发展过程中发现,血凝抑制、病毒中和及补体结合抗体以不同速率发展;对本研究及其他观察结果所得数据的仔细分析得出结论,这些抗体活性并非以恒定比例存在且相互独立。讨论了这一观察结果及上述其他观察结果的意义。