Abstract：
BPZE1 is a live, attenuated pertussis vaccine derived from B. pertussis strain Tohama I modified by genetic removal or inactivation of 3 B. pertussis toxins: pertussis toxin, dermonecrotic toxin, and tracheal cytotoxin. This Phase 2a study evaluated the safety and immunogenicity of liquid or lyophilized BPZE1 vaccine administered intranasally by needleless tuberculin syringe or mucosal atomization device (VaxINatorTM) at two dose levels.
Fifty healthy male and non-pregnant female participants 18-49 years of age were enrolled. Participants were randomized 3:3:3:1 to a single lyophilized dose of 107 colony forming units (CFU) BPZE1, 109 CFU BPZE1, placebo via VaxINator device, or a single liquid dose of 109 CFU BPZE1 via tuberculin syringe. Reactogenicity was assessed for 14 days. Blood was obtained pre-vaccination; on Day 8 (safety); and on Days 15, 29, and 181 (immunogenicity). Nasal wick and swab samples were obtained at baseline and on Days 29 and 181 for assessment of mucosal antibody responses and clearance of BPZE1.
Across all groups, 35/50 (70 %) experienced at least one local adverse event (AE) and 31/50 (62 %) experienced at least one systemic AE, with similar AE frequencies observed between the highest 109 CFU BPZE1 and placebo groups. There were no severe or serious AEs during the study. At Day 29, seroconversion (≥2-fold rise from baseline in serum IgG or IgA) to at least 2 pertussis antigens was observed in 73 % in the 109 CFU BPZE1 VaxINator group, 60 % in the 109 CFU BPZE1 group delivered via tuberculin syringe, 27 % of participants in the 107 CFU BPZE1 VaxINator group, and 20 % in the placebo VaxINator group. No participants were colonized with BPZE1 at Day 29 post vaccination.
Lyophilized BPZE1 vaccine was well tolerated and immunogenic at the highest dose (109 CFU) delivered intranasally by VaxINator device and was not associated with any SAEs or prolonged shedding of BPZE1. Further evaluation of BPZE1 is warranted.
Fifty healthy male and non-pregnant female participants 18-49 years of age were enrolled. Participants were randomized 3:3:3:1 to a single lyophilized dose of 107 colony forming units (CFU) BPZE1, 109 CFU BPZE1, placebo via VaxINator device, or a single liquid dose of 109 CFU BPZE1 via tuberculin syringe. Reactogenicity was assessed for 14 days. Blood was obtained pre-vaccination; on Day 8 (safety); and on Days 15, 29, and 181 (immunogenicity). Nasal wick and swab samples were obtained at baseline and on Days 29 and 181 for assessment of mucosal antibody responses and clearance of BPZE1.
Across all groups, 35/50 (70 %) experienced at least one local adverse event (AE) and 31/50 (62 %) experienced at least one systemic AE, with similar AE frequencies observed between the highest 109 CFU BPZE1 and placebo groups. There were no severe or serious AEs during the study. At Day 29, seroconversion (≥2-fold rise from baseline in serum IgG or IgA) to at least 2 pertussis antigens was observed in 73 % in the 109 CFU BPZE1 VaxINator group, 60 % in the 109 CFU BPZE1 group delivered via tuberculin syringe, 27 % of participants in the 107 CFU BPZE1 VaxINator group, and 20 % in the placebo VaxINator group. No participants were colonized with BPZE1 at Day 29 post vaccination.
Lyophilized BPZE1 vaccine was well tolerated and immunogenic at the highest dose (109 CFU) delivered intranasally by VaxINator device and was not associated with any SAEs or prolonged shedding of BPZE1. Further evaluation of BPZE1 is warranted.
摘要：
BPZE1是活的,百日咳减毒疫苗来源于百日咳杆菌菌株TohamaI，通过基因去除或失活3百日咳毒素：百日咳毒素，皮肤坏死毒素，和气管细胞毒素.该2a期研究评估了通过无针结核菌素注射器或粘膜雾化装置（VaxINatorTM）以两种剂量水平鼻内施用的液体或冻干BPZE1疫苗的安全性和免疫原性。
50名18-49岁的健康男性和非怀孕女性参与者被纳入。参与者被随机分为3：3：3：1，接受单剂量的107个菌落形成单位（CFU）BPZE1，109CFUBPZE1，通过VaxINator装置安慰剂，或通过结核菌素注射器单个液体剂量的109CFUBPZE1。评估反应性14天。在疫苗接种前;在第8天(安全性);和在第15、29和181天(免疫原性)获得血液。在基线和第29天和第181天获得鼻芯和拭子样品,用于评估粘膜抗体应答和BPZE1的清除。
在所有组中，35/50（70％）经历了至少一个局部不良事件（AE），31/50（62％）经历了至少一个全身性AE，在最高的109CFUBPZE1和安慰剂组之间观察到相似的AE频率。在研究期间没有严重或严重的AE。在第29天，在109CFUBPZE1VaxINator组中，观察到至少2种百日咳抗原的血清转化（血清IgG或IgA从基线升高≥2倍）为73％，109CFUBPZE1组通过结核菌素注射器递送60%，107CFUBPZE1VaxINator组中27％的参与者，安慰剂VaxINator组为20%。在接种后第29天,没有参与者用BPZE1定殖。
冻干的BPZE1疫苗在通过VaxINator装置鼻内递送的最高剂量(109CFU)下具有良好的耐受性和免疫原性,并且与任何SAE或BPZE1的延长脱落无关。BPZE1的进一步评估是必要的。
50名18-49岁的健康男性和非怀孕女性参与者被纳入。参与者被随机分为3：3：3：1，接受单剂量的107个菌落形成单位（CFU）BPZE1，109CFUBPZE1，通过VaxINator装置安慰剂，或通过结核菌素注射器单个液体剂量的109CFUBPZE1。评估反应性14天。在疫苗接种前;在第8天(安全性);和在第15、29和181天(免疫原性)获得血液。在基线和第29天和第181天获得鼻芯和拭子样品,用于评估粘膜抗体应答和BPZE1的清除。
在所有组中，35/50（70％）经历了至少一个局部不良事件（AE），31/50（62％）经历了至少一个全身性AE，在最高的109CFUBPZE1和安慰剂组之间观察到相似的AE频率。在研究期间没有严重或严重的AE。在第29天，在109CFUBPZE1VaxINator组中，观察到至少2种百日咳抗原的血清转化（血清IgG或IgA从基线升高≥2倍）为73％，109CFUBPZE1组通过结核菌素注射器递送60%，107CFUBPZE1VaxINator组中27％的参与者，安慰剂VaxINator组为20%。在接种后第29天,没有参与者用BPZE1定殖。
冻干的BPZE1疫苗在通过VaxINator装置鼻内递送的最高剂量(109CFU)下具有良好的耐受性和免疫原性,并且与任何SAE或BPZE1的延长脱落无关。BPZE1的进一步评估是必要的。
