Laboratories of the International Health Division of The Rockefeller Foundation, New York.
J Exp Med. 1944 Dec 1;80(6):477-91. doi: 10.1084/jem.80.6.477.
Subcutaneous inoculation, of PR8 allantoic fluid, or watery suspensions of the virus obtained from allantoic fluid by high-speed centrifugation or by elution after adsorption on red cells induced serum antibodies in experimental animals, which reached the highest levels within 2 weeks after inoculation and were gradually lost thereafter. The addition of killed acid-fast bacteria (Myco. tuberculosis or butyricum), paraffin oil, and a proprietary adsorption base (Falba) to form a stable water-in-oil emulsion of influenza virus suspensions greatly enhanced and maintained immunity and antibody response to the virus. These adjuvants provided a much more effective method of increasing antibody production to the virus than the use of concentrated preparations of virus alone. Paraffin oil and Falba without the acid-fast bacilli were less effective as adjuvants, although the antibody levels induced were higher than those produced by watery suspensions of the virus and were maintained at a constant level for at least 6 months. Myco. butyricum appeared to be more effective in producing antibodies against the virus than the tubercle bacilli in the emulsions of paraffin oil and Falba. Immunization with these adjuvants and suspensions of influenza virus obtained from allantoic fluid induced antibodies not only against the virus but against antigenic material contained in normal allantoic fluid, although the latter titers were considerably lower. A suspension of influenza virus (sedimented by high-speed centrifugation) and Myco. butyricum in sesame oil induced about four times as much antibody as when the virus was suspended in saline, in sesame oil alone, or in combination with typhoid bacilli.
皮下接种 PR8 尿囊液,或通过高速离心或通过吸附在红细胞上洗脱后从尿囊液中获得的病毒的水样悬浮液,可在实验动物中诱导血清抗体,这些抗体在接种后 2 周内达到最高水平,此后逐渐下降。将灭活的抗酸细菌(结核分枝杆菌或丁酸)、石蜡油和专有的吸附剂(Falba)添加到流感病毒悬浮液中形成稳定的水包油乳液,极大地增强和维持了对病毒的免疫力和抗体反应。这些佐剂比单独使用浓缩病毒制剂更有效地增加了对病毒的抗体产生。没有抗酸细菌的石蜡油和 Falba 作为佐剂的效果较差,尽管诱导的抗体水平高于病毒的水样悬浮液,但至少可维持 6 个月的稳定水平。在石蜡油和 Falba 乳剂中,丁酸分枝杆菌似乎比结核分枝杆菌更有效地产生针对病毒的抗体。用这些佐剂和从尿囊液中获得的流感病毒悬浮液进行免疫接种不仅可诱导针对病毒的抗体,还可诱导针对正常尿囊液中所含抗原物质的抗体,尽管后者的效价要低得多。在芝麻油中悬浮流感病毒(通过高速离心沉淀)和丁酸分枝杆菌可诱导的抗体量约为病毒悬浮在盐水中、单独悬浮在芝麻油中或与伤寒杆菌混合时的四倍。