Endsley Janice J, Roth James A, Ridpath Julia, Neill John
Department of Veterinary Pathobiology, University of Missouri-Columbia, MO 65201, USA.
Biologicals. 2003 Jun;31(2):123-5. doi: 10.1016/s1045-1056(03)00027-7.
Bovine viral diarrhoea virus (BVDV) contributes significantly to health-related economic losses in the beef and dairy industry. Antibodies of maternal origin can be protective against BVDV infection, however, calves with low titres of maternal antibody or that do not receive colostrum may be at risk for acute BVDV infection. Interference by high titres of maternal antibodies prevents the development of an antibody response following vaccination with either a killed or attenuated BVDV vaccine. However, the T cell mediated immune response to BVDV may be generated in the absence of a detectable serum neutralizing antibody response. Two trials were conducted to evaluate the potential to elicit T cell mediated immune responses to BVDV in calves with circulating maternal antibody to BVDV. In the first trial, calves with high levels of circulating maternal antibody to BVDV 1 and BVDV 2 were experimentally infected with BVDV 2 (strain 1373) at two to five weeks of age. The T-cell mediated immune responses of the experimentally infected calves and non-infected calves were monitored monthly until circulating maternal antibody was no longer detectable in either treatment group. Calves experimentally infected with BVDV developed BVDV specific CD4(+), CD8(+), and delta T cell responses while high levels of maternal antibody were circulating. A second challenge with BVDV 2 (strain 1373) was performed in the experimentally infected and control calves once maternal antibody could no longer be detected. Previous exposure to BVDV in the presence of maternal antibody protected calves from clinical signs of acute BVDV infection compared to the control calves. In the second trial, three groups of calves with circulating maternal antibody to BVDV were given either a modified live vaccine (MLV) containing BVDV 1 and BVDV 2, a killed vaccine containing BVDV 1 and BVDV 2, or no vaccine, at seven weeks of age. Serum neutralizing antibody levels and antigen specific T cell responses were monitored for 14 weeks following vaccination. Calves vaccinated with MLV BVDV developed BVDV 1 and BVDV 2 specific CD4(+)T cell responses, and BVDV 2 specific gammadelta T cell responses, in the presence of maternal antibody. Vaccination with killed BVDV did not result in the generation of measurable antigen specific T cell immune responses. In this trial, a second vaccination was performed at 14 weeks to determine whether an anamnestic antibody response could be generated when calves were vaccinated in the presence of maternal antibody. Calves vaccinated with either a MLV or killed BVDV vaccine while they had maternal antibody developed an anamnestic antibody response to BVDV 2 upon subsequent vaccination. The results of these trials indicate that vaccinating young calves against BVD while maternal antibody is present may generate BVDV specific memory T and B cells. The data also demonstrated that seronegative calves with memory T and B cells specific for BVDV may be immune to challenge with virulent BVDV.
牛病毒性腹泻病毒（BVDV）给牛肉和乳制品行业造成了巨大的与健康相关的经济损失。母源抗体可预防BVDV感染，然而，母源抗体滴度低或未摄入初乳的犊牛可能有急性BVDV感染风险。高滴度母源抗体的干扰会阻止用灭活或减毒BVDV疫苗接种后抗体反应的产生。然而，在没有可检测到的血清中和抗体反应的情况下，也可能产生针对BVDV的T细胞介导的免疫反应。进行了两项试验，以评估在具有循环母源BVDV抗体的犊牛中引发针对BVDV的T细胞介导免疫反应的潜力。在第一项试验中，对具有高水平循环母源抗BVDV 1和BVDV 2抗体的犊牛，在2至5周龄时用BVDV 2（1373株）进行实验性感染。每月监测实验性感染犊牛和未感染犊牛的T细胞介导免疫反应，直到两个治疗组中均无法再检测到循环母源抗体。在母源抗体循环时，实验性感染BVDV的犊牛产生了BVDV特异性CD4(+)、CD8(+)和δT细胞反应。一旦无法再检测到母源抗体，就在实验性感染和对照犊牛中再次用BVDV 2（1373株）进行攻击。与对照犊牛相比，在母源抗体存在的情况下先前接触过BVDV可使犊牛免受急性BVDV感染的临床症状。在第二项试验中，三组具有循环母源BVDV抗体的犊牛在7周龄时分别接种含有BVDV 1和BVDV 2的改良活疫苗（MLV）、含有BVDV 1和BVDV 2的灭活疫苗或不接种疫苗。接种后14周监测血清中和抗体水平和抗原特异性T细胞反应。在母源抗体存在的情况下，接种MLV BVDV的犊牛产生了BVDV 1和BVDV 2特异性CD4(+)T细胞反应以及BVDV 2特异性γδT细胞反应。接种灭活BVDV未产生可测量的抗原特异性T细胞免疫反应。在该试验中，在14周时进行了第二次接种，以确定在犊牛存在母源抗体时接种疫苗是否可产生回忆性抗体反应。在具有母源抗体时接种MLV或灭活BVDV疫苗的犊牛在随后接种时对BVDV 2产生了回忆性抗体反应。这些试验的结果表明，在存在母源抗体时给幼龄犊牛接种BVD疫苗可能会产生BVDV特异性记忆T细胞和B细胞。数据还表明，具有BVDV特异性记忆T细胞和B细胞的血清阴性犊牛可能对强毒BVDV的攻击具有免疫力。
