Huebner Robin E, Nicol Mark, Mothupi Rosalia, Käyhty Helena, Mbelle Nontombi, Khomo Esther, Klugman Keith P
Respiratory and Meningeal Pathogens Research Unit of the Medical Research Council, National Health Laboratory Service and the University of the Witwatersrand, Johannesburg, South Africa.
Vaccine. 2004 Dec 21;23(6):802-6. doi: 10.1016/j.vaccine.2004.06.052.
High vaccine cost has limited use of conjugate vaccines in the developing world where the disease burden is greatest. Fixed fractional doses of Haemophilus influenzae type b (Hib) vaccines have been shown to be immunogenic, but dose responses of these vaccines in humans are needed to determine the lowest immunogenic dose as an option for lowering vaccine cost. We randomized children to receive one of five doses (0.625, 1.25, 2.5, 5.0 and 10 microg) of either a diphtheria CRM197 or tetanus toxoid-conjugated Hib vaccine. The children received a primary three-dose series at 6, 10, and 14 weeks of age and a booster dose at 9 months. Anti-PRP IgG antibodies were measured at each vaccination, at 18 weeks, and at one week following the booster dose. Concentrations of > or =1.25 microg of HibCRM197 vaccine produced mean anti-PRP responses at 18 weeks of > or =5.72 microg/ml and > or =0.15 microg/ml was achieved in >98% of the children with at least 79% reaching anti-PRP concentrations of > or =1.0 microg/ml. Concentrations of > or =1.25 microg of Hib-tetanus vaccine produced mean anti-PRP responses at 18 weeks of > or =8.63 microg/ml and > or =0.15 microg/ml was achieved in 100% of the children with at least 88.9% reaching anti-PRP concentrations of > or =1.0 microg/ml. While mean antibody concentrations after either vaccine decreased over time, the proportion of children with antibody levels of > or =0.15 microg/ml had not changed significantly at the 9 month measurement. Immunologic memory was demonstrated by significant increases in mean antibody concentrations one week after the booster dose for doses > or =1.25 microg of HibCRM197 and Hib-tetanus to mean concentrations > or =37.71 and 16.07 microg/ml, respectively. There were no differences in antibody responses for vaccine doses > or =1.25 microg of the same vaccine or between the same concentrations of the two different vaccines. Our data suggest that doses of these vaccines of > or =1.25 microg may be sufficient to stimulate an immune response that offers both short and longer term protection from invasive Hib disease.
高昂的疫苗成本限制了结合疫苗在疾病负担最重的发展中世界的使用。已证明b型流感嗜血杆菌（Hib）疫苗的固定分剂量具有免疫原性，但需要了解这些疫苗在人体中的剂量反应，以确定最低免疫原性剂量，作为降低疫苗成本的一种选择。我们将儿童随机分组，使其接受五种剂量（0.625、1.25、2.5、5.0和10微克）之一的白喉CRM197或破伤风类毒素结合Hib疫苗。儿童在6、10和14周龄时接受三剂基础免疫，在9个月时接受一剂加强免疫。在每次接种疫苗时、18周时以及加强免疫后一周测量抗PRP IgG抗体。HibCRM197疫苗剂量≥1.25微克时，在18周时产生的平均抗PRP反应≥5.72微克/毫升，98%以上的儿童抗PRP浓度≥0.15微克/毫升，至少79%的儿童抗PRP浓度≥1.0微克/毫升。Hib-破伤风疫苗剂量≥1.25微克时，在18周时产生的平均抗PRP反应≥8.63微克/毫升，100%的儿童抗PRP浓度≥0.15微克/毫升，至少88.9%的儿童抗PRP浓度≥1.0微克/毫升。虽然两种疫苗接种后的平均抗体浓度均随时间下降，但在9个月测量时，抗体水平≥0.15微克/毫升的儿童比例没有显著变化。对于HibCRM197和Hib-破伤风疫苗，剂量≥1.25微克时，加强免疫后一周平均抗体浓度显著增加，分别达到≥37.71和16.07微克/毫升，证明了免疫记忆。相同疫苗剂量≥1.25微克时或两种不同疫苗相同浓度之间的抗体反应没有差异。我们的数据表明，这些疫苗剂量≥1.25微克可能足以刺激免疫反应，提供短期和长期预防侵袭性Hib疾病的保护。
