Tang Roderick S, Spaete Richard R, Thompson Mark W, MacPhail Mia, Guzzetta Jeanne M, Ryan Patricia C, Reisinger Keith, Chandler Patricia, Hilty Milo, Walker Robert E, Gomez Margarita M, Losonsky Genevieve A
MedImmune, 297 North Bernardo Avenue, Mountain View, CA 94043, USA.
Vaccine. 2008 Nov 25;26(50):6373-82. doi: 10.1016/j.vaccine.2008.09.018. Epub 2008 Sep 24.
MEDI-534 is a bivalent live attenuated vaccine candidate against human respiratory syncytial virus (hRSV) and human parainfluenza virus type 3 (hPIV3) that was previously shown to be immunogenic and to protect rodents and African green monkeys from wild-type (wt) hRSV challenge. We performed further preclinical evaluations to address the safety of MEDI-534 prior to human testing. MEDI-534 did not predispose rodents to enhanced RSV disease following wt-RSV challenge, and the tissue tropism of the chimeric virus was confined to the respiratory tract. Representative clinical trial material did not produce toxicity in rats. In adults, MEDI-534 was highly restricted in replication, did not boost RSV and PIV3 antibody titers, and produced no medically significant vaccine-related adverse events thereby warranting further evaluation in pediatric populations.
MEDI-534是一种针对人呼吸道合胞病毒（hRSV）和3型人副流感病毒（hPIV3）的二价减毒活疫苗候选物，此前已证明其具有免疫原性，并能保护啮齿动物和非洲绿猴免受野生型（wt）hRSV攻击。我们进行了进一步的临床前评估，以确定MEDI-534在人体试验前的安全性。在受到wt-RSV攻击后，MEDI-534不会使啮齿动物易患加重的RSV疾病，并且嵌合病毒的组织嗜性局限于呼吸道。代表性的临床试验材料在大鼠中未产生毒性。在成年人中，MEDI-534的复制受到高度限制，不会提高RSV和PIV3抗体滴度，也不会产生具有医学意义的疫苗相关不良事件，因此有必要在儿科人群中进行进一步评估。
