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Experiments on Vaccination of Human Beings against Epidemic Influenza

机译:人类预防流行性感冒疫苗的实验

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Studies have been reported on the vaccination of human beings against influenza A and B in regard to (1) the effect of single and multiple doses of vaccine; (2) comparison between allantoic-fluid vaccines and concentrates prepared therefrom; (3) the persistence of elevated antibody levels; and (4) the effects of adjuvants on the antibody response.1. (1) There was no added effect on repeated intramuscular injection of vaccine, i.e., one injection of allantoic-fluid vaccine gave as good a geometric mean antibody response as three injections at weekly intervals. Inhalation of vaccine in addition to one intramuscular injection, likewise, failed to increase the antibody response.2. (2) Concentrated vaccines prepared by precipitation with protamine gave higher geometric mean antibody levels than allantoic-fluid vaccines. Three ml of allantoic fluid, in turn, resulted in higher titers than 1 ml doses. Results, reported elsewhere, of experiments on infection of human beings with influenza virus suggested that subjects with antibody titers of greater than 1:128 were “probably immune,” those with lower levels, “potentially susceptible” to the disease. Classification of the subjects in the various groups according to this suggestion showed little difference in protection afforded by the concentrated preparation and the 3 ml dose of allantoic-fluid vaccine.3. (3) Although the geometric mean antibody levels 2 weeks after vaccination were increasingly higher with the increase in the dose of antigen injected, this difference tended to become less obvious in 3 months, and by the end of 6 months all groups were practically alike.4. (4) Protamine did not seem to exert an adjuvant effect. Emulsion of the vaccine in Falba and mineral oil, on the other hand, was highly effective in increasing and prolonging the antibody response. Practically all subjects in this series passed the “threshold antibody level” of 1:128 within 2 to 3 months, whereas in the controls injected with slightly larger amounts of vaccine in saline solution, only 70 per cent ever reached the “protective level” in 2 weeks at the time of maximal response. One year after vaccination with the adjuvants the geometric mean antibody levels both for influenza A and B were still above the maxima obtained in the control series. After 18 months, this was still true for the influenza B reactions, but no more for the influenza A titer. However, in this case the geometric mean was still 3 times higher than the pre-vaccination level. The titers in the control series receiving vaccine in saline solution had returned to the pre-vaccination level in the case of influenza A within one year, whereas the influenza B titers were still above the initial level at the end of 18 months, but 70 per cent of the subjects had titers below 1:128. These data suggest that protection may be afforded for at least 2 winters following vaccination with mineral oil as adjuvant. The technic requires further study to decrease the incidence of abscess formation which was noted in 2 out of 80 subjects or of 120 sites of injection.
机译:关于针对甲型和乙型流感的人类疫苗接种的研究已有报道,涉及以下方面:(1)单剂和多剂疫苗的作用; (2)尿囊液疫苗和由其制备的浓缩物之间的比较; (3)持续升高的抗体水平; (4)佐剂对抗体应答的影响。 (1)重复肌肉注射疫苗没有附加效果,即,一次注射尿囊液疫苗产生的几何平均抗体反应与每周一次的三次注射一样好。同样,除了肌肉注射外,还吸入疫苗未能增加抗体应答。2。 (2)用鱼精蛋白沉淀制备的浓缩疫苗比尿囊液疫苗具有更高的几何平均抗体水平。反过来,三毫升尿囊液产生的滴度高于1毫升剂量。在其他地方报道的有关人类感染流感病毒的实验结果表明,抗体效价大于1:128的受试者“可能是免疫的”,水平较低的受试者“可能对该病易感”。根据这一建议,各组受试者的分类显示,浓缩制剂和3ml剂量的尿囊液疫苗所提供的保护作用几乎没有差异。3。 (3)尽管接种疫苗后2周的几何平均抗体水平随着注射抗原剂量的增加而越来越高,但这种差异在3个月内趋于不明显,并且到6个月结束时,所有组实际上都是相似的。 4。 (4)鱼精蛋白似乎没有发挥辅助作用。另一方面,在Falba和矿物油中乳化疫苗可有效提高和延长抗体应答。实际上,该系列中的所有受试者在2到3个月内均通过了1:128的“阈值抗体水平”,而在对照中注射了稍多一点盐溶液疫苗的对照组中,只有70%的受试者达到了“保护水平”。达到最大反应时的2周。接种佐剂后一年,甲型和乙型流感病毒的几何平均抗体水平仍高于对照系列的最大值。 18个月后,对于乙型流感病毒反应仍然如此,但对于甲型流感病毒滴度则不再适用。但是,在这种情况下,几何平均值仍比疫苗接种前水平高3倍。在甲型流感的情况下,接受盐溶液疫苗接种的对照系列滴度在一年内恢复到疫苗接种前的水平,而乙型流感的滴度在18个月末仍高于初始水平,但每70滴百分之一的受试者滴度低于1:128。这些数据表明,用矿物油作为佐剂疫苗接种后,至少可以在2个冬天进行保护。该技术需要进一步研究以减少脓肿形成的发生率,在80名受试者中有2名或120个注射部位中发现了脓肿。

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