McIntosh K, Arbeter A M, Stahl M K, Orr I A, Hodes D S, Ellis E F
Pediatr Res. 1974 Jul;8(7):689-96. doi: 10.1203/00006450-197407000-00001.
Extract: Two live “attenuated” respiratory syncytial virus (RSV) vaccines were administered intranasally and by aerosol in placebo-controlled trials among asthmatic children hospitalized at National Jewish Hospital and Research Center (NJH). The first vaccine, a 26° -adapted RSV vaccine, was given to 28 children, and a placebo control was given to 25. Twenty-one of 28 vaccinees (75%) had “takes,” as judged by virus shedding and/or rises in serum antibody and/or rises in nasal secretion neutralizing activity. No excess in wheezing was attributable to the vaccine administration, although there was a high background level of acute respiratory symptoms in both vaccinees and control subjects. In an outbreak of natural RSV infection which occurred some months after the vaccine was given, there was some evidence that those who received the vaccine less than 4 months before exposure to wild virus were protected against reinfection. Protection was not evident when this interval was greater than 4 months. The second vaccine, a temperature-sensitive mutant strain (ts-1), was administered to 22 children, and placebo to 21. Thirteen children (59%) had “takes.” In vaccinees under 6 years of age, 7 of 7 had “takes.” Again, no excess wheezing was seen in vaccinees as compared with control subjects, although there was some evidence that upper respiratory symptoms were more frequent in younger vaccinees. Four of 10 vaccinees shed virus with temperature-sensitive characteristics somewhat different from those of the vaccine strain. Vaccine virus was demonstrated to spread to uninoculated or placebo control children. Natural RSV challenge did not occur during the period of study. Speculation: One of two live “attenuated” RSV vaccines may have produced a brief period of protection against natural infection. This finding offers hope that such live vaccines might prevent disease in selected children over a critical time period, such as infants for the 1st year of life, or allergic or asthmatic children during periods of epidemic prevalence. Asthmatic children did not appear to develop symptoms of wheezing after attenuated RSV infection. This finding suggests that the mechanism of wheezing in asthmatic children with RSV infection may be dependent on, among other factors, the virulence of the virus strain (perhaps its capacity to replicate in and, possibly, invade the lower respiratory tract), rather than on an allergic response to antigens introduced into, and limited to, the upper airway. In view of the spread of the ts-1 vaccine and its apparent loss of temperature sensitivity in some vaccinees, the vaccine may have had the potential for reversion to virulence and hence initiation of epidemic disease. These characteristics are undesirable in live respiratory virus vaccines and should, if possible, be avoided in the development of future such vaccines.
在国家犹太医院和研究中心（NJH）住院的哮喘儿童中进行的安慰剂对照试验中，两种减毒活呼吸道合胞病毒（RSV）疫苗通过鼻内和雾化方式给药。第一种疫苗是26°适应的RSV疫苗，给予28名儿童，25名儿童给予安慰剂对照。根据病毒排出和/或血清抗体升高和/或鼻分泌物中和活性升高判断，28名接种疫苗者中有21名（75%）出现“接种反应”。尽管疫苗接种者和对照受试者的急性呼吸道症状背景水平都很高，但没有发现因接种疫苗导致喘息过度增加。在接种疫苗几个月后发生的一次自然RSV感染暴发中，有证据表明，在接触野生病毒前不到4个月接种疫苗的人受到了再感染的保护。当这个间隔时间大于4个月时，保护作用不明显。第二种疫苗是一种温度敏感突变株（ts-1），给予22名儿童，21名儿童给予安慰剂。13名儿童（59%）出现“接种反应”。在6岁以下的接种疫苗者中，7名中有7名出现“接种反应”。同样，与对照受试者相比，接种疫苗者中没有出现喘息过度增加的情况，尽管有证据表明年龄较小的接种疫苗者上呼吸道症状更频繁。10名接种疫苗者中有4名排出的病毒温度敏感特性与疫苗株略有不同。已证明疫苗病毒传播到未接种疫苗或接受安慰剂对照的儿童中。在研究期间未发生自然RSV攻击。推测：两种减毒活RSV疫苗之一可能产生了一段针对自然感染的短暂保护期。这一发现带来了希望，即这种活疫苗可能在关键时间段内预防特定儿童的疾病，例如1岁以内婴儿，或在流行高发期的过敏或哮喘儿童。哮喘儿童在感染减毒RSV后似乎没有出现喘息症状。这一发现表明，RSV感染的哮喘儿童喘息机制可能取决于多种因素，包括病毒株的毒力（可能是其在下呼吸道复制并可能侵入的能力），而不是对上呼吸道引入并局限于上呼吸道的抗原的过敏反应。鉴于ts-1疫苗的传播及其在一些接种疫苗者中明显丧失温度敏感性，该疫苗可能具有恢复毒力并因此引发流行病的可能性。这些特性在活呼吸道病毒疫苗中是不可取的，在未来此类疫苗的研发中应尽可能避免。
