Intercell USA, Inc., 20 Firstfield Road, Gaithersburg, MD 20878, USA.
Vaccine. 2009 Dec 30;27 Suppl 6:G60-6. doi: 10.1016/j.vaccine.2009.10.031.
The use of adjuvants to enhance the immune response to novel pandemic influenza vaccine candidates may overcome the poor immune responses seen in immunologically naïve populations. The confluence of a highly pathogenic H5N1 influenza virus and the widespread absence of pre-existing immunity has driven the search for effective strategies for immunization in the face of a lethal pandemic. The potent adjuvant, heat labile enterotoxin from E. coli (LT), placed over the immunization site in a patch, is a novel adjuvant strategy for immune enhancement, and was evaluated using an H5N1 injectable vaccine.
In this observer-blind, placebo-controlled clinical study, 500 healthy adults 18-49 years of age were randomized to receive two intramuscular doses of A/Vietnam/1194/2004 A/H5N1 vaccine (5microg, 15microg or 45microg) or placebo (saline) 21 days apart. For each of the influenza vaccine doses, a 50microg LT adjuvant patch was applied over the injection site at either the second or both immunizations and the HI responses (titers) were compared to H5N1 vaccine alone. The study's primary endpoint was safety, and secondary immunogenicity endpoints were evaluated using European (CHMP) licensure criteria.
The vaccine was safe and well tolerated, and subjects generally lacked pre-existing H5N1 immunity. The single-dose injection 45microg HA/LT patch regimen met all CHMP licensure criteria, including a 73% seroprotection rate compared to 49% seroprotection without a patch. Significant adjuvant effects were seen at all HA doses on Day 21. By contrast, only modest adjuvant effects were observed with the boosting regimen in subjects first primed with H5N1 alone and given the adjuvant patch only on the second immunization. The two-injection/two-patch 45microg HA regimen achieved significantly higher titers and GMFR compared to injection alone (GMFR 33.1 vs. 16.9, HI 226 vs. 94, p<0.05) and a 94% seroprotection rate.
The LT adjuvant patch placed over the injection site was safe, significantly enhanced the immune response to an H5N1 candidate vaccine, and achieved a 73% seroprotection rate after a single dose. The LT adjuvant patch has more modest benefits in recently primed populations similar to other candidate vaccine adjuvants, but a two-dose patch plus injection regimen resulted in robust HI responses.
使用佐剂来增强对新型大流行性流感疫苗候选物的免疫反应，可能克服在免疫原性未成熟的人群中观察到的免疫反应不佳的问题。高致病性 H5N1 流感病毒的出现和广泛缺乏预先存在的免疫力，促使人们寻找有效的免疫策略，以应对致命的大流行。将大肠杆菌不耐热肠毒素（LT）置于免疫部位的贴剂中是一种增强免疫的新型佐剂策略，并用 H5N1 可注射疫苗进行了评估。
在这项观察者盲法、安慰剂对照的临床研究中，将 500 名 18-49 岁的健康成年人随机分为两组，分别接受两剂肌肉内注射 A/Vietnam/1194/2004 A/H5N1 疫苗（5μg、15μg 或 45μg）或安慰剂（生理盐水），间隔 21 天。对于每剂流感疫苗，在第二次免疫或两次免疫时，将 50μg LT 佐剂贴剂贴在注射部位上，并用 HI 反应（滴度）与单独使用 H5N1 疫苗进行比较。该研究的主要终点是安全性，次要免疫原性终点则根据欧洲（CHMP）许可标准进行评估。
疫苗安全且耐受良好，受试者通常缺乏预先存在的 H5N1 免疫力。单次注射 45μgHA/LT 贴剂方案符合所有 CHMP 许可标准，包括与不贴剂的 49%保护率相比，具有 73%的血清保护率。在第 21 天，所有 HA 剂量均观察到明显的佐剂作用。相比之下，仅在首次仅接受 H5N1 疫苗接种并仅在第二次免疫时给予佐剂贴剂的受试者中，增强方案观察到适度的佐剂作用。两剂/两贴 45μgHA 方案与单独注射相比，达到了更高的滴度和 GMFR（GMFR 33.1 对 16.9，HI 226 对 94，p<0.05），并达到了 94%的血清保护率。
置于注射部位的 LT 佐剂贴剂安全，可显著增强对 H5N1 候选疫苗的免疫反应，单次剂量后可达到 73%的血清保护率。在类似于其他候选疫苗佐剂的新近免疫人群中，LT 佐剂贴剂的作用更为适度，但两剂贴剂加注射方案可产生强大的 HI 反应。
