Bertley F M N, Ibrahim S A, Libman M, Ward B J
Center for the Study of Host Resistance, Montreal General Hospital, McGill University, 1650 Cedar Avenue, Montreal, QC, Canada H3G 1A4.
Vaccine. 2004 Dec 9;23(4):444-9. doi: 10.1016/j.vaccine.2004.06.021.
Early or low dose antigen exposure can prime the immune system for subsequent responses; the so-called "prime-boost" effect. In the context of a Sudanese measles vaccine trial, we assessed whether or not such early exposure could influence the response to revaccination. Children received either Connaught high titer vaccine (CN: n = 53; 10(4.7)pfu) or meningococcal A + C vaccine as a placebo (MEN: n = 58) at 5 months of age. At 9 months of age, all received standard titer Schwarz vaccine (SCH: 10(3.9)pfu). Neutralizing antibodies were measured before initial vaccination and at 9 months of age (plaque reduction neutralization assay (PRN)) and again at 5 years of age (syncytium inhibition assay (SIA)). Lymphoproliferative responses to measles virus (MV) antigens were evaluated at 5 years of age. Eleven of the 53 CN-SCH children (21%) had sub-protective neutralizing antibody titers prior to revaccination (log PRN 1.5 +/- 0.03 versus 2.9 +/- 0.07 in the remaining 42 children; P < 0.004). Maternal antibody titers at the time of initial vaccination in these 11 were high (PRN 2.44 +/- 0.12 versus 1.9 +/- 0.04; P < 0.0001). At 5 years of age, neutralizing antibodies were comparable in the 11 CN-SCH poor responders (log SIA 2.1 +/- 0.09), the remaining CN-SCH children (2.2 +/- 0.06) and the MEN-SCH group vaccinated only once at 9 months of age (2.25 +/- 0.06). In contrast, 7/11 of the CN-SCH poor responders (64%) had stimulation indices (SI) > 3 in response to MV antigens at 5 years of age (SI 3.1 +/- 0.6) compared with only 14% in the remaining children of the CN-SCH group (2.0 +/- 0.3; P = 0.05) and 8% in the MEN-SCH group (1.4 +/- 0.2; P < 0.0003). These data suggest that early measles vaccination in the presence of maternal antibodies can sometimes prime for a balanced humoral and cellular immune response to subsequent revaccination.
早期或低剂量抗原暴露可使免疫系统为后续反应做好准备；即所谓的“初免-加强”效应。在一项苏丹麻疹疫苗试验中，我们评估了这种早期暴露是否会影响再次接种疫苗的反应。儿童在5月龄时分别接种了诺康高滴度疫苗（CN组：n = 53；10(4.7)pfu）或A + C型脑膜炎球菌疫苗作为安慰剂（MEN组：n = 58）。在9月龄时，所有儿童均接种了标准滴度的施瓦茨疫苗（SCH：10(3.9)pfu）。在初次接种疫苗前、9月龄时（空斑减少中和试验（PRN））以及5岁时（合胞体抑制试验（SIA））测量中和抗体。在5岁时评估对麻疹病毒（MV）抗原的淋巴细胞增殖反应。53名CN-SCH组儿童中有11名（21%）在再次接种疫苗前中和抗体滴度低于保护水平（log PRN为1.5 +/- 0.03，其余42名儿童为2.9 +/- 0.07；P < 0.004）。这11名儿童初次接种疫苗时的母源抗体滴度较高（PRN为2.44 +/- 0.12，其余儿童为1.9 +/- 0.04；P < 0.0001）。在5岁时，11名CN-SCH组低反应者（log SIA为2.1 +/- 0.09）、其余CN-SCH组儿童（2.2 +/- 0.06）以及仅在9月龄时接种过一次疫苗的MEN-SCH组儿童（2.25 +/- 0.06）的中和抗体水平相当。相比之下，5岁时，CN-SCH组11名低反应者中有7名（64%）对MV抗原的刺激指数（SI）> 3（SI为3.1 +/- 0.6），而CN-SCH组其余儿童中这一比例仅为14%（2.0 +/- 0.3；P = 0.05），MEN-SCH组为8%（1.4 +/- 0.2；P < 0.0003）。这些数据表明，在存在母源抗体的情况下早期接种麻疹疫苗有时可为后续再次接种疫苗引发平衡的体液免疫和细胞免疫反应做好准备。
