Hospital Universitari Joan XXIII, C. Dr. Mallafrè Guasch 4, 43007, Tarragona, Spain.
CIBERES, Hospital Universitari Vall d'Hebron, Passeig Vall d'Hebron, 119, 08035, Barcelona, Spain.
Crit Care. 2017 Feb 4;21(1):22. doi: 10.1186/s13054-017-1601-9.
Currently, no vaccine against Pseudomonas is available. IC43 is a new, recombinant, protein (OprF/I)-based vaccine against the opportunistic pathogen, Pseudomonas aeruginosa, a major cause of serious hospital-acquired infections. IC43 has proven immunogenicity and tolerability in healthy volunteers, patients with burns, and patients with chronic lung diseases. In order to assess the immunogenicity and safety of IC43 in patients who are most at risk of acquiring Pseudomonas infections, it was evaluated in mechanically ventilated ICU patients.
We conducted a randomized, placebo-controlled, partially blinded study in mechanically ventilated ICU patients. The immunogenicity of IC43 at day 14 was determined as the primary endpoint, and safety, efficacy against P. aeruginosa infections, and all-cause mortality were evaluated as secondary endpoints. Vaccinations (100 μg or 200 μg IC43 with adjuvant, or 100 μg IC43 without adjuvant, or placebo) were given twice in a 7-day interval and patients were followed up for 90 days.
Higher OprF/I IgG antibody titers were seen at day 14 for all IC43 groups versus placebo (P < 0.0001). Seroconversion (≥4-fold increase in OprF/I IgG titer from days 0 to 14) was highest with 100 μg IC43 without adjuvant (80.6%). There were no significant differences in P. aeruginosa infection rates, with a low rate of invasive infections (pneumonia or bacteremia) in the IC43 groups (11.2-14.0%). Serious adverse events (SAEs) considered possibly related to therapy were reported by 2 patients (1.9%) in the group of 100 µg IC43 with adjuvant. Both SAEs resolved and no deaths were related to study treatment. Local tolerability symptoms were mild and rare (<5% of patients), a low rate of treatment-related treatment-emergent adverse events (3.1-10.6%) was observed in the IC43 groups.
This phase II study has shown that IC43 vaccination of ventilated ICU patients produced a significant immunogenic effect. P. aeruginosa infection rates did not differ significantly between groups. In the absence of any difference in immune response following administration of 100 μg IC43 without adjuvant compared with 200 μg IC43 with adjuvant, the 100 μg dose without adjuvant was considered for further testing of its possible benefit of improved outcomes. There were no safety or mortality concerns.
ClinicalTrials.gov, NCT00876252 . Registered on 3 April 2009.
目前尚无针对铜绿假单胞菌的疫苗。IC43 是一种新型重组蛋白（OprF/I）疫苗，用于治疗机会致病菌铜绿假单胞菌，该菌是严重医院获得性感染的主要病因。IC43 在健康志愿者、烧伤患者和慢性肺部疾病患者中已被证实具有免疫原性和耐受性。为了评估 IC43 在最易感染铜绿假单胞菌的患者中的免疫原性和安全性，我们在机械通气 ICU 患者中进行了评估。
我们对机械通气的 ICU 患者进行了一项随机、安慰剂对照、部分盲法研究。以第 14 天的 IC43 免疫原性作为主要终点，评估安全性、针对铜绿假单胞菌感染的疗效以及全因死亡率作为次要终点。接种（100μg 或 200μg IC43 加佐剂、100μg IC43 不加佐剂或安慰剂），在 7 天间隔内进行两次，患者随访 90 天。
与安慰剂相比，所有 IC43 组在第 14 天的 OprF/I IgG 抗体滴度均升高（P<0.0001）。100μg 无佐剂 IC43 组的血清转化率（OprF/I IgG 滴度从第 0 天到第 14 天增加≥4 倍）最高（80.6%）。铜绿假单胞菌感染率无显著差异，IC43 组侵袭性感染（肺炎或菌血症）发生率较低（11.2%-14.0%）。2 例（1.9%）接受 100μg 加佐剂 IC43 治疗的患者报告了认为可能与治疗相关的严重不良事件（SAE）。这 2 例 SAE 均已解决，且无死亡与研究治疗相关。局部耐受性症状轻微且罕见（<5%的患者），IC43 组治疗中出现的与治疗相关的治疗突发不良事件率为 3.1%-10.6%。
这项 II 期研究表明，对机械通气的 ICU 患者进行 IC43 疫苗接种可产生显著的免疫效果。各组之间的铜绿假单胞菌感染率无显著差异。与 200μg 加佐剂 IC43 相比，100μg 无佐剂 IC43 的免疫反应无差异，因此考虑使用 100μg 无佐剂 IC43 进行进一步研究，以评估其改善结局的可能益处。没有安全性或死亡率方面的担忧。
ClinicalTrials.gov，NCT00876252。2009 年 4 月 3 日注册。
