Cape Stephen, Chaudhari Amol, Vaidya Vivek, Mulay Ravindra, Agarkhedkar Shalaka, Shermer Charles, Collins Marcus, Anderson Raydel, Agarkhedkar Sharad, Kulkarni Prasad S, Winston Scott, Sievers Robert, Dhere Rajeev M, Gunale Bhagwat, Powell Ken, Rota Paul A, Papania Mark
Padmashri D Y Patil Medical College, Pune, India.
Serum Institute of India Ltd, Pune, India.
Vaccine. 2014 Nov 28;32(50):6791-7. doi: 10.1016/j.vaccine.2014.09.071. Epub 2014 Oct 22.
Measles is a highly infectious respiratory disease which causes 122,000 deaths annually. Although measles vaccine is extremely safe and effective, vaccine coverage could be improved by a vaccine that is more easily administered and transported. We developed an inhalable dry powder measles vaccine (MVDP) and two delivery devices, and demonstrated safety, immunogenicity, and efficacy of the vaccine in preclinical studies. Here we report the first clinical trial of MVDP delivered by inhalation.
Sixty adult males aged 18 to 45 years, seropositive for measles antibody, were enrolled in this controlled Phase I clinical study. Subjects were randomly assigned in 1:1:1 ratio to receive either MVDP by Puffhaler(®) or by Solovent™ devices or the licensed subcutaneous measles vaccine. Adverse events (AEs) were recorded with diary cards until day 28 post-vaccination and subjects were followed for 180 days post-vaccination to assess potential serious long term adverse events. Measles antibody was measured 7 days before vaccination and at days 21 and 77 after vaccination by ELISA and a plaque reduction neutralization test.
All subjects completed the study according to protocol. Most subjects had high levels of baseline measles antibody. No adverse events were reported. MVDP produced serologic responses similar to subcutaneous vaccination.
MVDP was well tolerated in all subjects. Most subjects had high baseline measles antibody titer which limited ability to measure the serologic responses, and may have limited the adverse events following vaccination. Additional studies in subjects without pre-existing measles antibody are needed to further elucidate the safety and immunogenicity of MVDP.
麻疹是一种具有高度传染性的呼吸道疾病，每年导致12.2万人死亡。尽管麻疹疫苗极其安全有效，但一种更易于给药和运输的疫苗可提高疫苗接种率。我们开发了一种可吸入干粉麻疹疫苗（MVDP）和两种给药装置，并在临床前研究中证明了该疫苗的安全性、免疫原性和有效性。在此，我们报告了通过吸入方式递送MVDP的首次临床试验。
60名年龄在18至45岁之间、麻疹抗体血清学阳性的成年男性参与了这项对照I期临床研究。受试者按1:1:1的比例随机分配，分别通过Puffhaler（®）或Solovent™装置接受MVDP，或接受许可的皮下麻疹疫苗。使用日记卡记录接种疫苗后28天内的不良事件（AE），并在接种疫苗后对受试者进行180天的随访，以评估潜在的严重长期不良事件。在接种疫苗前7天以及接种疫苗后第21天和第77天，通过酶联免疫吸附测定（ELISA）和蚀斑减少中和试验测量麻疹抗体。
所有受试者均按照方案完成了研究。大多数受试者的麻疹抗体基线水平较高。未报告不良事件。MVDP产生的血清学反应与皮下接种相似。
所有受试者对MVDP耐受性良好。大多数受试者的麻疹抗体基线滴度较高，这限制了测量血清学反应的能力，也可能限制了接种疫苗后的不良事件。需要在没有预先存在麻疹抗体的受试者中进行更多研究，以进一步阐明MVDP的安全性和免疫原性。
