Rennels M B, Edwards K M, Keyserling H L, Reisinger K S, Hogerman D A, Madore D V, Chang I, Paradiso P R, Malinoski F J, Kimura A
Center for Vaccine Development and Department of Pediatrics, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Pediatrics. 1998 Apr;101(4 Pt 1):604-11. doi: 10.1542/peds.101.4.604.
To determine the safety and immunogenicity of heptavalent pneumococcal saccharide vaccine (serotypes 4, 6B, 9V, 14, 18C, 19F, 23F) individually conjugated to CRM197 (PNCRM7), administered at 2, 4, 6, and 12 to 15 months of age.
Two hundred twelve healthy 2-month-old infants were equally randomized to receive four consecutive doses of PNCRM7 or an investigational meningococcal group C conjugate vaccine, which served as a control. Concomitantly administered routine vaccines were oral polio vaccine and combined diphtheria toxoid, tetanus toxoid, and whole cell pertussis vaccine/Haemophilus influenzae type b vaccine consisting of capsular oligosaccharides conjugated to CRM197 (DTP/HbOC) at 2, 4, and 6 months, and either measles-mumps-rubella vaccine or HbOC at 12 to 15 months. Active safety surveillance was conducted for 3 days after each dose. Antibody concentrations to each of the 7 pneumococcal serotypes were measured by enzyme-linked immunosorbent assay prevaccination, after doses two and three, prebooster, and postbooster.
Significantly fewer children experienced local reactions at the PNCRM7 injection site than at the DTP/HbOC site. There was no increase in the incidence or severity of local reactions at the PNCRM7 site with increasing doses of vaccine. Mild to moderate postvaccination fever was common in both the PNCRM7 and control vaccine groups, however DTP/HbOC was administered concurrently. All 7 vaccine serotypes were immunogenic. The kinetics of the immune responses were serotype-specific. After three doses of PNCRM7, between 92% to 100% of children had >/=0.15 microg/mL of antibody, and 51% to 90% achieved a level of >/=1 microg/mL against specific serotypes. A booster dose of PNCRM7 resulted in a brisk anamnestic response to all 7 vaccine serotypes, demonstrating effective stimulation of T-cell memory by the primary series of vaccinations.
Primary immunization followed by a booster dose of PNCRM7 seemed to be acceptably safe and resulted in significant rises in antibody to all 7 serotypes. Implications. Studies to assess vaccine efficacy of PNCRM7 for prevention of systemic disease, nasopharyngeal colonization, and acute otitis media are in progress. If PNCRM7 proves to be protective, there is the potential to prevent up to 85% of invasive pneumococcal disease occurring in US children.
确定七价肺炎球菌多糖疫苗（4、6B、9V、14、18C、19F、23F血清型）分别与CRM197偶联（PNCRM7），在2、4、6以及12至15月龄时接种的安全性和免疫原性。
212名健康的2月龄婴儿被平均随机分为两组，分别连续接种四剂PNCRM7或一种作为对照的研究用C群脑膜炎球菌结合疫苗。同时接种的常规疫苗为口服脊髓灰质炎疫苗，以及在2、4和6月龄时接种的由与CRM197偶联的荚膜寡糖组成的白喉类毒素、破伤风类毒素和全细胞百日咳疫苗/ b型流感嗜血杆菌疫苗（DTP/HbOC），在12至15月龄时接种麻疹-腮腺炎-风疹疫苗或HbOC。每次接种后进行3天的主动安全性监测。在接种前、第二剂和第三剂后、加强免疫前以及加强免疫后，通过酶联免疫吸附测定法测量针对7种肺炎球菌血清型中每种血清型的抗体浓度。
与DTP/HbOC接种部位相比，PNCRM7接种部位出现局部反应的儿童明显更少。随着疫苗剂量增加，PNCRM7接种部位局部反应的发生率或严重程度没有增加。PNCRM7组和对照疫苗组接种疫苗后出现轻至中度发热均较为常见，不过DTP/HbOC是同时接种的。所有7种疫苗血清型均具有免疫原性。免疫反应的动力学具有血清型特异性。接种三剂PNCRM7后，92%至100%的儿童针对特定血清型的抗体水平≥0.15μg/mL，51%至90%的儿童达到≥1μg/mL的水平。一剂PNCRM7加强免疫导致对所有7种疫苗血清型出现快速的回忆反应，表明初次系列接种有效刺激了T细胞记忆。
初次免疫后接种一剂PNCRM7似乎安全性良好，且能使所有7种血清型的抗体显著升高。意义。评估PNCRM7预防全身性疾病、鼻咽部定植和急性中耳炎疫苗效力的研究正在进行中。如果PNCRM7被证明具有保护作用，则有可能预防美国儿童中高达85%的侵袭性肺炎球菌疾病。
