ABSTRACT

Background: We assessed the safety and immunogenicity of 2 + 1 infant regimens initiated with the 13-valent pneumococcal conjugate vaccine (PCV13) and completed with the pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV).

Methods: This partially blinded study randomized 6–12-week-old infants to receive two-dose priming and a booster (at ages 2, 4, 12–15 months) with: PCV13 at priming and PHiD-CV at boosting (PPS); PCV13 then PHiD-CV at priming and PHiD-CV at boosting (PSS); or PHiD-CV at priming and boosting (SSS control). All analyses were descriptive, i.e., no statistical significance tests were done.

Results: The total vaccinated cohort at priming comprised 294 infants. Grade 3 adverse events were reported after 8.7% (PPS), 11.4% (PSS), and 16.9% (SSS) of primary doses (primary objective). No serious adverse events were considered vaccination-related. For most PHiD-CV serotypes, observed percentages of children reaching antibody concentrations ≥0.2 µg/mL and opsonophagocytic activity (OPA) titers above cutoffs were similar across groups 1 month post-priming and post-booster. Observed geometric mean antibody concentrations and OPA titers were lower for some PHiD-CV serotypes with the mixed regimens than with PHiD-CV only, especially for PSS. However, no tests of statistical significance were performed.

Conclusions: Immunogenicity of the two mixed PCV13/PHiD-CV regimens seemed mostly similar to that of a PHiD-CV-only series, although observed antibody GMCs and OPA GMTs for some PHiD-CV serotypes were lower. No safety concerns were raised. The clinical relevance of the observed differences is unknown.

Clinical trial registration: ClinicalTrials.gov: NCT01641133

摘要

背景：我们评估了由13价肺炎球菌结合疫苗（PCV13）起始并由肺炎球菌不可分型流感嗜血杆菌D结合蛋白疫苗（PHiD-CV）实施的2 + 1婴儿治疗的安全性和免疫原性。

方法：该部分盲研究随机分配了6-12周龄的婴儿接受两次剂量的初次免疫和加强免疫（在2、4、4、12-15个月大），其中：初次免疫PCV13和初次免疫的PHiD-CV（PPS） ; 然后PCV13在启动时为PHiD-CV，在增压时为PHiD-CV（PSS）；在启动和增压（SSS控制）时为PHiD-CV。所有分析均为描述性，即未进行统计显着性检验。

结果：初次接种的总队列包括294名婴儿。在主要剂量（主要目标）的8.7％（PPS），11.4％（PSS）和16.9％（SSS）之后报告了3级不良事件。没有严重不良事件被认为与疫苗接种有关。对于大多数PHiD-CV血清型，在初免后和加强后1个月的各组中观察到的达到抗体浓度≥0.2µg / mL的儿童的百分比，以及超过临界值的调理吞噬活性（OPA）滴度。对于某些混合方案的PHiD-CV血清型，观察到的几何平均抗体浓度和OPA滴度低于仅PHiD-CV的血清型，尤其是PSS。但是，没有进行统计显着性检验。

结论：两种混合PCV13 / PHiD-CV方案的免疫原性似乎与仅纯PHiD-CV系列的相似，尽管对于某些PHiD-CV血清型观察到的抗体GMC和OPA GMT较低。没有提出安全问题。所观察到的差异的临床相关性未知。

临床试验注册： ClinicalTrials.gov：NCT01641133