Lee C Y, Thipphawong J, Huang L M, Lee P I, Chiu H H, Lin W, Debois H, Harrison D, Xie F, Barreto L
National Taiwan University, Taipei, Taiwan.
Pediatrics. 1999 Jan;103(1):25-30. doi: 10.1542/peds.103.1.25.
Immunologic interference particular to the Haemophilus influenzae type b (Hib) response has been observed with previous acellular pertussis-Hib combination vaccines. To test this hypothesis a clinical trial to assess the safety and immunogenicity of a five-component (pertussis toxoid [PT], filamentous hemagglutinin [FHA], pertactin [PRN], and fimbriae 2 and 3 [FIM]), pertussis vaccine combined with diphtheria and tetanus toxoids (DTaP) when given simultaneously with a lyophilized Hib-tetanus toxoid conjugate vaccine (PRP-T) in infants at 2, 4, 6, and 18 months of age was conducted. The study compared two methods of administration: both vaccines combined in a single syringe and administered as a single injection, or both vaccines administered concurrently but at separate sites of injection.
Healthy 2-month-old infants were enrolled at the National Taiwan University Hospital. DTaP, PRP-T, and oral poliomyelitis vaccine (OPV) were given at 2, 4, 6, and 18 months. Reaction information was collected by telephone 2 days after each vaccination. Serum was collected at 2, 6, 7, 18, and 19 months of age.
One hundred thirty-five healthy infants were enrolled in Taiwan, of which 127 (94%) completed the 18-month booster: 68 received the combined vaccine and 67 the separate vaccines. All vaccines were well tolerated. No differences in rates of local and systemic reactions were seen between the two methods of administration. No serious adverse events were reported. Serologic responses were comparable between the groups. Pertussis responses (enzyme-liked immunoabsorbant assay units [EU]/mL) at 7 months were, for combined versus separate, PT (131 vs 105), FHA (116 vs 116), PRN (100 vs 77), and FIM (922 vs 702). At 19 months, pertussis results were, for combined versus separate, PT (216 vs 182), FHA (203 vs 200), PRN (263 vs 197), and FIM (892 vs 732). Only the 7-month PT response in the combined group was significantly higher (combined 131 EU/mL vs separate 105 EU/mL). After the third dose (age 6 months), all subjects achieved serologic serum antibody levels indicative of protection against Hib, diphtheria, tetanus, and poliovirus types 1, 2, and 3. In fact, 96% of children had anti-PRP levels indicative of protection (>/=0.15 microgram/mL) against Hib after only two doses. At 7 months, anti-PRP geometric mean titer values were 11.8 micrograms/mL in the combined group compared with 13.0 micrograms/mL in the separate group. The anti-PRP geometric mean titers after the 18-month booster were 58.5 micrograms/mL in the combined group versus 55.3 micrograms/mL in the separate group.
The five-component DTaP vaccine may be combined with PRP-T vaccine without clinically significant immunologic interaction when given in a 2-, 4-, 6-, and 18-month schedule.
以往的无细胞百日咳 - b型流感嗜血杆菌（Hib）联合疫苗出现过特定于b型流感嗜血杆菌（Hib）反应的免疫干扰现象。为验证这一假设，开展了一项临床试验，以评估在2、4、6和18月龄婴儿中同时接种五组分（百日咳类毒素[PT]、丝状血凝素[FHA]、百日咳杆菌黏附素[PRN]以及2型和3型菌毛[FIM]）百日咳疫苗与白喉和破伤风类毒素联合疫苗（DTaP）和冻干Hib - 破伤风类毒素结合疫苗（PRP - T）时的安全性和免疫原性。该研究比较了两种接种方法：两种疫苗混合于一支注射器中作为单次注射接种，或者两种疫苗同时接种但在不同注射部位。
国立台湾大学医院招募了健康的2月龄婴儿。在2、4、6和18月龄时接种DTaP、PRP - T和口服脊髓灰质炎疫苗（OPV）。每次接种后2天通过电话收集反应信息。在2、6、7、18和19月龄时采集血清。
台湾共招募了135名健康婴儿，其中127名（94%）完成了18月龄加强接种：68名接种了联合疫苗，67名接种了分开的疫苗。所有疫苗耐受性良好。两种接种方法在局部和全身反应发生率上未见差异。未报告严重不良事件。两组间血清学反应相当。7月龄时百日咳反应（酶联免疫吸附测定单位[EU]/mL），联合接种组与分开接种组相比，PT（131对105）、FHA（116对116）、PRN（100对77）和FIM（922对702）。19月龄时，百日咳反应结果，联合接种组与分开接种组相比，PT（216对182）、FHA（203对200）、PRN（263对197）和FIM（892对732）。仅联合接种组7月龄时的PT反应显著更高（联合接种组131 EU/mL对分开接种组105 EU/mL）。第三次接种（6月龄）后，所有受试者血清学抗体水平均达到可预防Hib、白喉、破伤风以及1、2和3型脊髓灰质炎病毒的水平。事实上，仅两剂后96%的儿童抗PRP水平达到可预防Hib的水平（≥0.15微克/毫升）。7月龄时，联合接种组抗PRP几何平均滴度值为11.8微克/毫升，分开接种组为13.0微克/毫升。18月龄加强接种后，联合接种组抗PRP几何平均滴度为58.5微克/毫升，分开接种组为55.3微克/毫升。
按照2、4、6和18月龄的接种程序，五组分DTaP疫苗与PRP - T疫苗联合接种时可能不存在具有临床意义的免疫相互作用。
