古巴七价肺炎球菌结合疫苗在健康婴儿中的安全性和免疫原性。I 期双盲随机对照试验结果。

Safety and immunogenicity of the Cuban heptavalent pneumococcal conjugate vaccine in healthy infants. Results from a double-blind randomized control trial Phase I.

机构信息

Children University Hospital "Juan Manuel Márquez", Marianao, Havana 11400, Cuba.

Finlay Vaccine Institute, 200 and 21 Street, Playa, Havana 11600, Cuba.

出版信息

Vaccine. 2018 Aug 6;36(32 Pt B):4944-4951. doi: 10.1016/j.vaccine.2018.05.027. Epub 2018 Jul 10.

DOI:10.1016/j.vaccine.2018.05.027

PMID:30005948

Abstract

BACKGROUND

Cuba has a new pneumococcal conjugate vaccine candidate (PCV7-TT). This study evaluates the safety and immunogenicity in healthy infants using 2p+1 vaccination schedule.

METHODS

A phase I, controlled, randomized and double blind clinical trial was designed. 30 unvaccinated healthy infants were included. 20 subjects were assigned to study group (PCV7-TT) and 10 to control group (Synflorix®) to receive the vaccines at 7, 8 months of age (primary series) and 11 months (booster dose). Blood samples were collected 30 days after second dose and post booster for antibodies measure analysis by ELISA and OPA. The statistics analysis included the frequency of occurrence for adverse events and the immune response. Non-parametric tests were used to compare the immune response. The clinical trial was published in the Cuban Public Register of Clinical Trials with code RPCEC00000173 available at http://registroclinico.sld.cu.

RESULTS

Overall, the safety profile of PCV7-TT was similar to Synflorix®. Local reactions were predominant and systemic events were mild in severity. Swelling and redness were frequently associated with PCV7-TT mainly after the first dose (50% and 40% respectively). 15% and 10% of subject reported severe swelling after first dose with PCV7-TT and after second dose with Synflorix®. Mild fever (≥38-≤39), vomiting and sleep disturb were the systemic events reported. 100% of infants achieved pneumococcal IgG antibody concentrations ≥0.35 µg/ml after booster dose for serotypes 1, 14, 18C and 19F in each vaccine group. For serotypes 5, 6B and 23F, more than 80% infants vaccinated with Synflorix® or PCV7-TT achieved protective IgG GMC ≥ 0.35 µg/ml after booster dose. OPA proportion's responders to the seven common serotypes were 89.5% or more after the primary dose and 100% after booster dose in vaccinated with PCV7-TT.

CONCLUSIONS

The Cuban PCV7-TT is safe, well tolerated and immunogenic in healthy infants.

摘要

背景

古巴有一种新的肺炎球菌结合疫苗候选物（PCV7-TT）。本研究采用 2p+1 免疫程序评估了健康婴儿的安全性和免疫原性。

方法

设计了一项 I 期、对照、随机、双盲临床试验。纳入 30 名未接种过疫苗的健康婴儿。20 名受试者被分配到研究组（PCV7-TT），10 名受试者被分配到对照组（Synflorix®），分别于 7 个月和 8 个月（基础免疫系列）和 11 个月（加强免疫）龄时接种疫苗。在第二次接种后 30 天和加强免疫后采集血样，通过 ELISA 和 OPA 分析抗体测量值。统计分析包括不良事件发生频率和免疫应答。使用非参数检验比较免疫应答。临床试验已在古巴临床试验公共登记处（http://registroclinico.sld.cu）以 RPCEC00000173 号公布。

结果

总体而言，PCV7-TT 的安全性与 Synflorix®相似。局部反应为主，全身事件均为轻度。肿胀和发红主要与 PCV7-TT 相关，主要发生在第一次接种后（分别为 50%和 40%）。PCV7-TT 组第一次和第二次接种后分别有 15%和 10%的受试者报告严重肿胀。报告的全身事件有轻度发热（≥38-≤39℃）、呕吐和睡眠障碍。加强免疫后，每组疫苗的血清型 1、14、18C 和 19F 的血清型 1 型 IgG 抗体浓度均达到≥0.35µg/ml（100%）。接种 Synflorix®或 PCV7-TT 的婴儿中，血清型 5、6B 和 23F 超过 80%的婴儿在加强免疫后获得保护性 IgG GMC≥0.35µg/ml。PCV7-TT 接种组七价常见血清型的 OPA 比例应答者在基础免疫后达到 89.5%或更高，在加强免疫后达到 100%。