Gwaltney J M, DeSanctis A N, Metzgar D P, Hendley J O
Am J Epidemiol. 1977 Mar;105(3):252-60. doi: 10.1093/oxfordjournals.aje.a112381.
Standard whole virus influenza vaccine (1974-1976) containing 700 chicken cell agglutinating (CCA) units of type A (Port Chalmers/1/75) or Port Chalmers plus Scotland/840/74) and 500 units of type B (HK/8/73) antigens was found to produce excessive systemic toxicity in adult volunteers. Using experimental monovalent A and B vaccines, most of the observed toxicity was shown to be associated with the B antigen. Injection of 500 CCA units or more of B vaccine was followed within 10-16 hours by malaise and chills in approximately one-third of vaccines. Chills, malaise, and local pain were more common in volunteers lacking prevaccination serum HI antibody than in those in whom this antibody was present. Toxicity was not related to the presence of endotoxin or bacterial contamination of vaccine; it appeared to be "intrinsic" to the viral antigen. The mechanism for the toxicity in man may be the same as the direct pyrogenic effect of influenza antigen for rabbits previously observed by others. Detoxification of the B antigen by prolonged exposure to formalin reduced the side effects of a 500 CCA unit dose to acceptable levels without impairing its antigenicity.
标准全病毒流感疫苗（1974 - 1976）含有700鸡胚细胞凝集（CCA）单位的甲型（查尔姆斯港/1/75或查尔姆斯港加苏格兰/840/74）和500单位的乙型（香港/8/73）抗原，发现在成年志愿者中会产生过度的全身毒性。使用实验性单价甲型和乙型疫苗，观察到的大多数毒性与乙型抗原有关。注射500个或更多CCA单位的乙型疫苗后，约三分之一的接种者在10 - 16小时内会出现不适和寒战。缺乏接种前血清血凝抑制（HI）抗体的志愿者比有该抗体的志愿者更常出现寒战、不适和局部疼痛。毒性与疫苗中内毒素的存在或细菌污染无关；它似乎是病毒抗原“固有的”。人体中毒的机制可能与其他人之前观察到的流感抗原对兔子的直接致热作用相同。通过长时间暴露于福尔马林对乙型抗原进行解毒，可将500个CCA单位剂量的副作用降低到可接受水平，而不损害其抗原性。
