Mangarule S, Palkar S, Mitra M, Ravi M D, Dubey A P, Moureau A, Jayanth M V, Patel D M, Ravinuthala S, Jagga S R, Patnaik B N, Jordanov E, Noriega F
Sanofi Healthcare India Private Ltd (SHIPL), Hyderabad, India.
Bharati Vidyapeeth Deemed University Medical College, Pune, India.
Vaccine X. 2022 Jan 10;10:100137. doi: 10.1016/j.jvacx.2021.100137. eCollection 2022 Apr.
Multivalent vaccines containing whole-cell pertussis (wP) antigens combined with established diphtheria (D), tetanus (T), hepatitis B (HB), type b (Hib), and inactivated poliomyelitis (IPV) antigens allow the provision of a high-quality, affordable DTwP-IPV-HB-PRP∼T vaccine.
Phase I/II, randomized, active-controlled, open-label study in healthy toddlers (Cohort I) and infants (Cohort II). Toddlers in Cohort I who had completed primary series D, T, P, HB, Hib, and polio vaccination received a booster dose of DTwP-IPV-HB-PRP∼T (N = 30) or DTwP-HB-PRP∼T + IPV (N = 15) vaccines at 15-18 months of age. After satisfactory review of safety data in Cohort I, infants in Cohort II received DTwP-IPV-HB-PRP∼T (N = 100) or DTwP-HB-PRP∼T + IPV (N = 50) at 6-8, 10-12, and 14-16 weeks of age. All infants in Cohort II had received previous oral polio and HB vaccines per country recommendations.
Booster and primary series vaccinations were well tolerated with no clinically significant differences between vaccine groups. Most adverse events were mild and resolved spontaneously; there were no vaccine-related serious adverse events and no deaths. In both vaccine groups, anti-D, anti-T, anti-HB, anti-Hib, and anti-polio 1, 2, and 3 seroprotection was 100% post-booster and post-primary series. For the pertussis antigens, booster response rate was > 86% in both groups. For the primary series, vaccine response rate was slightly higher for DTwP-IPV-HB-PRP∼T than DTwP-HB-PRP∼T + IPV for anti-PT (80.2% and 70.8%) and anti-FHA (81.3% and 68.8%), slightly lower for anti-PRN (72.5% and 81.3%), and similar in each group for anti-FIM (95.6% and 97.9%).
This study demonstrated a good safety and immunogenicity profile of the hexavalent DTwP-IPV-HB-PRP∼T vaccine for infant primary series vaccination at 6-8, 10-12, and 14-16 weeks of age and booster vaccination at 15-18 months of age and supported progression to the next development phase.
含有全细胞百日咳（wP）抗原并与已有的白喉（D）、破伤风（T）、乙型肝炎（HB）、b型流感嗜血杆菌（Hib）和灭活脊髓灰质炎（IPV）抗原相结合的多价疫苗，能够提供高质量、价格可承受的DTwP-IPV-HB-PRP∼T疫苗。
在健康幼儿（队列I）和婴儿（队列II）中进行的I/II期随机、活性对照、开放标签研究。队列I中已完成D、T、P、HB、Hib和脊髓灰质炎基础免疫接种的幼儿在15至18月龄时接受一剂DTwP-IPV-HB-PRP∼T（N = 30）或DTwP-HB-PRP∼T + IPV（N = 15）疫苗的加强免疫。在对队列I的安全性数据进行满意审查后，队列II中的婴儿在6至8周、10至12周和14至16周龄时接受DTwP-IPV-HB-PRP∼T（N = 100）或DTwP-HB-PRP∼T + IPV（N = 50）。队列II中的所有婴儿均已按照各国建议接种过口服脊髓灰质炎疫苗和HB疫苗。
加强免疫和基础免疫接种耐受性良好，疫苗组之间无临床显著差异。大多数不良事件为轻度且可自发缓解；无疫苗相关严重不良事件及死亡。在两个疫苗组中，加强免疫和基础免疫接种后抗-D、抗-T、抗-HB、抗-Hib以及抗脊髓灰质炎1、2和3的血清保护率均为100%。对于百日咳抗原，两组的加强免疫应答率均>86%。对于基础免疫，DTwP-IPV-HB-PRP∼T组的抗百日咳毒素（PT）（80.2%和70.8%）和抗丝状血凝素（FHA）（81.3%和68.8%）疫苗应答率略高于DTwP-HB-PRP∼T + IPV组，抗百日咳核糖核酸酶（PRN）应答率略低（72.5%和81.3%），抗菌毛蛋白（FIM）应答率在每组中相似（95.6%和97.9%）。
本研究证明了六价DTwP-IPV-HB-PRP∼T疫苗在6至8周、10至12周和14至16周龄婴儿基础免疫接种以及15至18月龄加强免疫接种时具有良好的安全性和免疫原性，支持进入下一研发阶段。
