Salat Jiri, Mikulasek Kamil, Larralde Osmany, Pokorna Formanova Petra, Chrdle Ales, Haviernik Jan, Elsterova Jana, Teislerova Dana, Palus Martin, Eyer Ludek, Zdrahal Zbynek, Petrik Juraj, Ruzek Daniel
Veterinary Research Institute, Hudcova 70, CZ-62100 Brno, Czech Republic.
Central European Institute of Technology, Masaryk University, Kamenice 753/5, CZ-62500 Brno, Czech Republic.
Vaccines (Basel). 2020 Feb 12;8(1):81. doi: 10.3390/vaccines8010081.
Vaccination against tick-borne encephalitis (TBE) is based on the use of formalin-inactivated, culture-derived whole-virus vaccines. Immune response following vaccination is primarily directed to the viral envelope (E) protein, the major viral surface antigen. In Europe, two TBE vaccines are available in adult and pediatric formulations, namely FSME-IMMUN (Pfizer) and Encepur (GlaxoSmithKline). Herein, we analyzed the content of these vaccines using mass spectrometry (MS). The MS analysis revealed that the Encepur vaccine contains not only proteins of the whole virus particle, but also viral non-structural protein 1 (NS1). MS analysis of the FSME-IMMUN vaccine failed due to the high content of human serum albumin used as a stabilizer in the vaccine. However, the presence of NS1 in FSME-IMMUN was confirmed by immunization of mice with six doses of this vaccine, which led to a robust anti-NS1 antibody response. NS1-specific Western blot analysis also detected anti-NS1 antibodies in sera of humans who received multiple doses of either of these two vaccines; however, most vaccinees who received ≤3 doses were negative for NS1-specific antibodies. The contribution of NS1-specific antibodies to protection against TBE was demonstrated by immunization of mice with purified NS1 antigen, which led to a significant ( < 0.01) prolongation of the mean survival time after lethal virus challenge. This indicates that stimulation of anti-NS1 immunity by the TBE vaccines may increase their protective effect.
蜱传脑炎（TBE）疫苗接种基于使用福尔马林灭活的、培养衍生的全病毒疫苗。接种疫苗后的免疫反应主要针对病毒包膜（E）蛋白，即主要的病毒表面抗原。在欧洲，有两种成人和儿童剂型的TBE疫苗可供使用，即FSME - IMMUN（辉瑞公司）和Encepur（葛兰素史克公司）。在此，我们使用质谱法（MS）分析了这些疫苗的成分。质谱分析显示，Encepur疫苗不仅含有全病毒颗粒的蛋白质，还含有病毒非结构蛋白1（NS1）。对FSME - IMMUN疫苗的质谱分析失败，原因是该疫苗中用作稳定剂的人血清白蛋白含量过高。然而，用六剂这种疫苗免疫小鼠证实了FSME - IMMUN中存在NS1，这引发了强烈的抗NS1抗体反应。NS1特异性蛋白质印迹分析还在接受这两种疫苗多剂接种的人的血清中检测到了抗NS1抗体；然而，大多数接受≤3剂疫苗的接种者的NS1特异性抗体呈阴性。用纯化的NS1抗原免疫小鼠证明了NS1特异性抗体对预防TBE的作用，这导致在致命病毒攻击后平均存活时间显著延长（<0.01）。这表明TBE疫苗刺激抗NS1免疫可能会增强其保护作用。
