A Clinical Trial of Entolimod a TLR-5 Adjuvant for Vaccines Using Diphtheria or Tetanus as Carrier Proteins.
A Clinical Trial of Entolimod a TLR-5 Adjuvant for Vaccines Using Diphtheria or Tetanus as Carrier Proteins.
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Entolimod A TLR-5佐剂的临床试验，使用白喉或破伤风作为载体蛋白进行疫苗。
DOI：
10.3390/vaccines10101592
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发表时间：
2022-09-22
期刊：
影响因子：
7.8
通讯作者：
Nielsen DA
中科院分区：
文献类型：
--
作者：
Kosten TR;Domingo CB;Haile CN;Nielsen DA
以前的抗药物疫苗未能通过临床试验，因为它们没有提供足够的抗体(AB)效价或持续时间，但新的佐剂同时提高了AB滴度和效力持续时间。这项临床试验评估了单剂商业破伤风-白喉(TD)疫苗接种后40名男性的AB滴度，其中15人随机接受TD，25人接受TD和TLR5佐剂Entolimod(Ent)的联合接种。ENT显著增加了抗白喉(DPT)的ABS(0.46比0.29IU/mL增加；n=40，p<；0.05)，但只有当基线TT AB低于3IU/mL(3.1比2.1IU/mL；n=20；p<；0.05)时，才能预防破伤风(TT)。这20名受试者服用Ent后抗-TT AB滴度也比未服用Ent时高出一倍(33%比82%)(p<；0.03)。抗Ent AB抗体水平较低，在重复应用Ent后似乎不太可能降低Ent疗效。医疗安全性很好，TLR5错义多态减少了抗DPT AB的产生，但Ent增加了抗DPT AB的滴度，使TRL5功能正常的受试者达到了诱导水平。对于抗药物疫苗，似乎有必要对像Ent这样的TLR5佐剂进行进一步的临床测试。
Anti-drug vaccines previously failed clinical trials because they did not provide a sufficient titer or duration of antibodies (AB), but new adjuvants enhance both AB titers and efficacy duration. This clinical trial assessed AB titers after a single booster of commercial tetanus-diphtheria (Td) vaccine in 40 males randomized as 15 to Td alone and 25 to Td combined with the TLR5 adjuvant, Entolimod (Ent). Ent significantly increased ABs against diphtheria (DPT) (0.46 vs. 0.29 IU/mL increase; n = 40, p < 0.05), but against tetanus (TT) only if baseline TT AB was below 3 IU/mL (3.1 vs. 2.1 IU/mL; n = 20; p < 0.05). These 20 participants also showed a two-fold increase in anti-TT AB titer more often when given Ent than non-Ent (33% vs. 82%) (p < 0.03). Anti-Ent AB was low and appeared unlikely to reduce Ent efficacy after repeated Ent administration. Medical safety was excellent, and a TLR5 missense polymorphism reduced anti-DPT AB production, but Ent increased anti-DPT AB titers to levels induced in subjects with genetically “normal” TRL5 functioning. Further clinical testing of TLR5 adjuvants like Ent seems warranted for anti-drug vaccines.
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