Saliba G S, Franklin S L, Jackson G G
J Clin Invest. 1968 Jun;47(6):1303-13. doi: 10.1172/JCI105822.
Through a series of controlled experiments in volunteers, quantitative aspects of infection, illness, and immunity to ECHO-11 virus were studied. ECHO-11 is a transmissable viral infection in man and equally infectious to the upper respiratory and the intestinal tracts. The rate of infection was directly related to the dose of virus exposure, but any infectious dose of virus produced illness in only about one-third of the infected subjects. The infectious dose for man varied over a billionfold range. Larger challenge doses caused no difference in the local symptoms at the portal of entry or in the peak severity of illness, but symptoms were more diverse and prolonged after a higher dose. Persons with asymptomatic infections became just as heavily infected as ill persons. In respiratory secretions from natural infection, the titer of infectious virus was found to be about 10(2) median infective doses in tissue culture (TCID(50))/ml. At this level, up to 40% of exposed contacts could be infected per milliliter of secretion. The observed rate of spread was 24%. This low-dose inoculum caused illness in 12% of volunteers but failed to elicit a significant antibody response in 93% or immunity to reinfection and another illness upon rechallenge. Larger doses of virus produced a longer excretion of virus and a significant increase in serum-neutralizing antibody. Nasal antibody was infrequently found. The principal effect of antibody was to decrease virus excretion and to shorten illness; it reduced the rate but did not prevent infection. Attempts to produce an asymptomatic enteric infection which would induce immunity failed.The characteristics of respiratory transmission with mild disease, recurrent infection, and illness without a detectable antibody response or solid immunity to reinfection, satisfy the epidemiologic conditions to establish ECHO-11 virus as one of the causes of the common cold.
通过在志愿者身上进行的一系列对照实验,对ECHO - 11病毒感染、发病及免疫的定量方面进行了研究。ECHO - 11是一种可在人类中传播的病毒感染,对上呼吸道和肠道具有同等传染性。感染率与病毒暴露剂量直接相关,但任何感染剂量的病毒仅在约三分之一的受感染受试者中引发疾病。人类的感染剂量变化范围超过十亿倍。较大的攻击剂量在进入门户处的局部症状或疾病的峰值严重程度方面没有差异,但较高剂量后症状更多样化且持续时间更长。无症状感染者的感染程度与患病者一样严重。在自然感染的呼吸道分泌物中,发现传染性病毒滴度约为每毫升组织培养(TCID50)10(2)个中位感染剂量。在此水平下,每毫升分泌物中高达40%的接触者可能被感染。观察到的传播率为24%。这种低剂量接种物使12%的志愿者患病,但在93%的志愿者中未能引发显著的抗体反应,也未能产生对再次感染的免疫力以及再次攻击时的另一次疾病。较大剂量的病毒导致病毒排泄时间更长,血清中和抗体显著增加。很少发现鼻腔抗体。抗体的主要作用是减少病毒排泄并缩短病程;它降低了感染率,但并未预防感染。试图产生能诱导免疫的无症状肠道感染的尝试失败了。呼吸道传播具有轻症、反复感染以及无可检测到的抗体反应或对再次感染的稳固免疫力的疾病等特征,满足将ECHO - 11病毒确立为普通感冒病因之一的流行病学条件。