Connors M, Collins P L, Firestone C Y, Murphy B R
Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892.
J Virol. 1991 Mar;65(3):1634-7. doi: 10.1128/JVI.65.3.1634-1637.1991.
The ability of recombinant vaccinia viruses that separately encoded 9 of the 10 known respiratory syncytial virus (RSV) proteins to induce resistance to RSV challenge was studied in BALB/c mice. Resistance was examined at two intervals following vaccination to examine early (day 9) as well as late (day 28) immunity. BALB/c mice were inoculated simultaneously by the intranasal and intraperitoneal routes with a recombinant vaccinia virus encoding one of the following RSV proteins: F, G, N, P, SH, M, 1B, 1C, or M2 (22K). A parainfluenza virus type 3 HN protein recombinant (Vac-HN) served as a negative control. One half of the mice were challenged with RSV intranasally on day 9, and the remaining animals were challenged on day 28 postvaccination. Mice previously immunized by infection with RSV, Vac-F, or Vac-G were completely or almost completely resistant to RSV challenge on both days. In contrast, immunization with Vac-HN, -P, -SH, -M, -1B, or -1C did not induce detectable resistance to RSV challenge. Mice previously infected with Vac-M2 or Vac-N exhibited significant but not complete resistance on day 9. However, in both cases resistance had largely waned by day 28 and was detectable only in mice immunized with Vac-M2. These results demonstrate that F and G proteins expressed by recombinant vaccinia viruses are the most effective RSV protective antigens. This study also suggests that RSV vaccines need only contain the F and G glycoproteins, because the immunity conferred by the other proteins is less effective and appears to wane rapidly with time.
在BALB/c小鼠中研究了分别编码10种已知呼吸道合胞病毒(RSV)蛋白中9种的重组痘苗病毒诱导抗RSV攻击的能力。在接种疫苗后的两个时间点检测抵抗力,以检查早期(第9天)和晚期(第28天)免疫情况。通过鼻内和腹腔内途径同时给BALB/c小鼠接种编码以下RSV蛋白之一的重组痘苗病毒:F、G、N、P、SH、M、1B、1C或M2(22K)。副流感病毒3型HN蛋白重组体(Vac-HN)用作阴性对照。一半小鼠在第9天经鼻内接种RSV进行攻击,其余动物在接种疫苗后第28天进行攻击。先前通过感染RSV、Vac-F或Vac-G免疫的小鼠在这两天对RSV攻击均完全或几乎完全具有抵抗力。相比之下,用Vac-HN、-P、-SH、-M、-1B或-1C免疫未诱导出可检测到的抗RSV攻击的抵抗力。先前感染Vac-M2或Vac-N的小鼠在第9天表现出显著但不完全的抵抗力。然而,在这两种情况下,到第28天抵抗力已大幅减弱,仅在用Vac-M2免疫的小鼠中可检测到。这些结果表明,重组痘苗病毒表达的F和G蛋白是最有效的RSV保护性抗原。本研究还表明,RSV疫苗只需包含F和G糖蛋白,因为其他蛋白赋予的免疫力效果较差,且似乎会随时间迅速减弱。