Sirivichayakul Chukiat, Chanthavanich Pornthep, Limkittikul Kriengsak, Siegrist Claire-Anne, Wijagkanalan Wassana, Chinwangso Pailinrut, Petre Jean, Hong Thai Pham, Chauhan Mukesh, Viviani Simonetta
a Department of Tropical Pediatrics , Faculty of Tropical Medicine, Mahidol University , Bangkok , Thailand.
b WHO Collaborating Center for Vaccine Immunology, Faculty of Medicine, University of Geneva , Geneva , Switzerland.
Hum Vaccin Immunother. 2017 Jan 2;13(1):136-143. doi: 10.1080/21645515.2016.1234555. Epub 2016 Sep 29.
An acellular Pertussis (aP) vaccine containing recombinant genetically detoxified Pertussis Toxin (PTgen), Filamentous Hemagglutinin (FHA) and Pertactin (PRN) has been developed by BioNet-Asia (BioNet). We present here the results of the first clinical study of this recombinant aP vaccine formulated alone or in combination with tetanus and diphtheria toxoids (TdaP).
A phase I/II, observer-blind, randomized controlled trial was conducted at Mahidol University in Bangkok, Thailand in healthy adult volunteers aged 18-35 y. The eligible volunteers were randomized to receive one dose of either BioNet's aP or Tetanus toxoid-reduced Diphtheria toxoid-acellular Pertussis (TdaP) vaccine, or the Tdap Adacel® vaccine in a 1:1:1 ratio. Safety follow-up was performed for one month. Immunogenicity was assessed at baseline, at 7 and 28 d after vaccination. Anti-PT, anti-FHA, anti-PRN, anti-tetanus and anti-diphtheria IgG antibodies were assessed by ELISA. Anti-PT neutralizing antibodies were assessed also by CHO cell assay.
A total of 60 subjects (20 per each vaccine group) were enrolled and included in the safety analysis. Safety laboratory parameters, incidence of local and systemic post-immunization reactions during 7 d after vaccination and incidence of adverse events during one month after vaccination were similar in the 3 vaccine groups. One month after vaccination, seroresponse rates of anti-PT, anti-FHA and anti-PRN IgG antibodies exceeded 78% in all vaccine groups. The anti-PT IgG, anti-FHA IgG, and anti-PT neutralizing antibody geometric mean titers (GMTs) were significantly higher following immunization with BioNet's aP and BioNet's TdaP than Adacel® (P< 0.05). The anti-PRN IgG, anti-tetanus and anti-diphtheria GMTs at one month after immunization were comparable in all vaccine groups. All subjects had seroprotective titers of anti-tetanus and anti-diphtheria antibodies at baseline.
In this first clinical study, PTgen-based BioNet's aP and TdaP vaccines showed a similar tolerability and safety profile to Adacel® and elicited significantly higher immune responses to PT and FHA.
BioNet-Asia（BioNet）研发了一种含有重组基因解毒百日咳毒素（PTgen）、丝状血凝素（FHA）和百日咳黏附素（PRN）的无细胞百日咳（aP）疫苗。我们在此展示了这种单独配制或与破伤风和白喉类毒素联合（TdaP）的重组aP疫苗的首次临床研究结果。
在泰国曼谷的玛希隆大学对18至35岁的健康成年志愿者进行了一项I/II期、观察者盲法、随机对照试验。符合条件的志愿者被随机以1:1:1的比例接受一剂BioNet的aP疫苗、破伤风类毒素减量白喉类毒素无细胞百日咳（TdaP）疫苗或Tdap Adacel®疫苗。进行了为期一个月的安全性随访。在接种疫苗后的基线、第7天和第28天评估免疫原性。通过酶联免疫吸附测定（ELISA）评估抗PT、抗FHA、抗PRN、抗破伤风和抗白喉IgG抗体。抗PT中和抗体也通过中国仓鼠卵巢（CHO）细胞测定进行评估。
总共60名受试者（每个疫苗组20名）入组并纳入安全性分析。3个疫苗组在安全性实验室参数、接种疫苗后7天内局部和全身免疫后反应的发生率以及接种疫苗后一个月内不良事件的发生率方面相似。接种疫苗一个月后，所有疫苗组中抗PT、抗FHA和抗PRN IgG抗体的血清反应率均超过78%。用BioNet的aP和BioNet的TdaP免疫后，抗PT IgG、抗FHA IgG和抗PT中和抗体几何平均滴度（GMT）显著高于Adacel®（P<0.05）。免疫后一个月时，所有疫苗组中抗PRN IgG、抗破伤风和抗白喉的GMT相当。所有受试者在基线时抗破伤风和抗白喉抗体均具有血清保护滴度。
在这项首次临床研究中，基于PTgen的BioNet的aP和TdaP疫苗显示出与Adacel®相似的耐受性和安全性概况，并引发了对PT和FHA显著更高的免疫反应。
