STUDY OF RESPIRATORY VIRUSES IN VOLUNTEERS

志愿者呼吸道病毒的研究

• 批准号: 6098910
• 负责人: Brian Murphy
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6098910
• 关键词: Paramyxovirus; Pneumovirus vaccine; Vero cells; active immunization; attenuated microorganism; child (0-11); clinical research; gene deletion mutation; human subject; human therapy evaluation; infant human (0-1 year); live vaccine; paramyxovirus vaccine; respiratory syncytial virus

Progress has been made toward the development of a trivalent live attenuated virus vaccine consisting of (1) a respiratory syncytial virus (RSV) subgroup A component; (2) an RSV subgroup B component; and (3) a parainfluenza virus type 3 (PIV3) vaccine component. After evaluation of five live attenuated subgroup A virus vaccine candidates, the RSV A2 subgroup A candidate cpts248/404 has been found to be satisfactorily attenuated, phenotypically stable, poorly transmissible, and immunogenic in seronegative infants and children over the age of six months. As a consequence of this favorable constellation of properties, we initiated studies in the target population of one month old infants for the first time in our live attenuated RSV vaccine program. The cpts248/404 vaccine candidate retained some residual mild reactogenicity for the upper respiratory tract of infants and a more attenuated derivative will need to be generated. However, the cpts248/404 virus did not cause fever, otitis media, pneumonia or bronchiolitis so we are close to achieving the level of attenuation needed for this target age group. Young infants infected with vaccine virus developed an immune response sufficient to restrict replication of a second dose of vaccine. The candidate vaccine was, for the most part, phenotypically stable. Thus, the human neonate can develop a protective immune response induced by a live attenuated vaccine candidate that is effective against RSV, albeit an attenuated version of RSV. The RSV subgroup B candidate vaccine, RSV B1 cp23, was found to be under-attenuated for use in fully susceptible infants and children and for this reason will not be pursued further. RSV subgroup B vaccines of the future will need to be chimeric recombinant viruses bearing the RSV subgroup B F and G protective antigens on a background of an attenuated subgroup A virus that was from cDNA. A live attenuated PIV3 candidate vaccine, JS cp45, produced by NIH was satisfactorily attenuated, immunogenic, and phenotypically stable in seronegative infants and children, and studies with simian Vero cell-grown vaccine produced by our CRADA partner, Wyeth-Lederle-Praxis, have been initiated this past year. The two preparations appear to be comparable in their behavior in seronegative infants and children. Once fully acceptable monovalent vaccines are identified, studies with bivalent or trivalent vaccines will be initiated.

在发展方面取得了进展 由（1）a组成的三价活衰减病毒疫苗 呼吸综合病毒（RSV）亚组成分； （2） RSV子组B组件； （3）3型Parainfluenza病毒 （PIV3）疫苗成分。评估五个活着的衰减后 亚组A候选病毒疫苗，RSV A2亚组A 候选人CPTS248/404被发现令人满意 衰减，表型稳定，可传播不良，并且 超过年龄的血清神经婴儿和儿童免疫原性 六个月。由于这个有利的星座 属性，我们在一个目标人群中启动了研究 在我们的现场衰减RSV中，第一次是一个月大的婴儿 疫苗计划。 CPTS248/404疫苗候选者保留了一些 婴儿上呼吸道的残留轻度反应性 需要产生更衰减的衍生物。 但是，CPTS248/404病毒不会引起发烧，中耳炎， 肺炎或支气管炎，因此我们接近达到 该目标年龄组需要衰减。年轻的婴儿感染 疫苗病毒产生的免疫反应足以 限制第二剂疫苗的复制。候选人 在大多数情况下，疫苗在表型上是稳定的。因此， 人类新生儿可以产生保护性免疫反应 由有效的RSV有效的活疫苗候选候选者 尽管是RSV的衰减版本。 RSV子组B 候选疫苗RSV B1 CP23被发现不足 用于完全易感的婴儿和儿童，因此 不会进一步追求。 RSV亚组B疫苗的未来 需要是带有RSV的嵌合重组病毒 亚组B F和G保护抗原在一个背景 减弱来自cDNA的亚组病毒。活着 NIH生产的PIV3候选疫苗JS CP45 令人满意地减弱，免疫原性和表型稳定 血清神经儿童和儿童，以及对Simian Vero进行的研究 我们的Crada合作伙伴生产的细胞生长疫苗， 韦斯·利德勒（Wyeth-LeDerle-Praxis）已于过去一年发起。两个 准备工作的行为似乎是可比的 血清神经婴儿和儿童。一旦完全可以接受的单价 识别疫苗，二价或三价疫苗的研究 将开始。