Pan Sung-Ching, Hsieh Szu-Min, Lin Chih-Feng, Hsu Yu-Shen, Chang Mingi, Chang Shan-Chwen
Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Department of Otolaryngology/Head and Neck Surgery, National Taiwan University Hospital, Taipei, Taiwan.
Vaccine. 2019 Mar 28;37(14):1994-2003. doi: 10.1016/j.vaccine.2019.02.006. Epub 2019 Mar 2.
A nasal influenza vaccine has been available only in a live attenuated form, which limits the range of recipients to immune-competent individuals. The present study evaluated a newly developed intranasal inactivated influenza vaccine with a novel adjuvant, heat-labile enterotoxin (LT) derived from E. coli (LTh(αK)).
The study was a randomized, double-blind, controlled phase I trial to evaluate the safety and immunogenicity of an intranasal vaccine containing the trivalent influenza HA antigen (7.5 µg each of A/California/7/09 (H1N1)-like virus, A/Victoria/210/2009 (H3N2) virus, and B/Brisbane/60/2008-like virus) in combination with 4 different doses of adjuvant LTh(αK) (7.5, 15, 30 or 45 μg) and 22.5 μg of influenza HA antigen alone (control vaccine). The vaccine was intranasally administered on Days 0 and 7. A safety evaluation commenced for 180 days, and hemagglutination inhibition (HI) antibody titers and nasal HA-specific IgA titers on Day 0 and Day 28 were assessed to determine whether an immunogenic response was elicited.
From November 2012 to September 2013, a total of 36 subjects were enrolled. Twenty-four subjects received an adjuvanted vaccine, and 12 subjects received a control vaccine. The most common adverse event (AE) was mild nasal discomfort, and systemic AEs were mild fatigue and headache. Only two subjects discontinued the study because of an AE (one had grade 3 fever, and one had nodal arrhythmia). In the group with 45 μg of LTh(αK), the seroprotection rates were 100%, 100% and 80%, and the nasal IgA conversion factors were 7.90, 7.46 and 12.27 for the A/H3N2, A/H1N1 and split B strains, respectively. Adjuvant LTh(αK) vaccine showed a significant enhancement in mucosal immunity in split B -specific IgA.
The intranasal inactivated influenza vaccine is generally safe, and the LTh(αK)-adjuvanted vaccine is more immunogenic than non-adjuvanted control vaccine. ClinicalTrials.gov Identifier: NCT03293732.
鼻内流感疫苗仅有一种减毒活疫苗形式，这使得接种对象仅限于免疫功能正常的个体。本研究评估了一种新开发的鼻内灭活流感疫苗，其含有一种新型佐剂，即源自大肠杆菌的不耐热肠毒素（LT）（LTh(αK)）。
该研究为一项随机、双盲、对照的I期试验，旨在评估一种鼻内疫苗的安全性和免疫原性。该疫苗含有三价流感血凝素抗原（A/加利福尼亚/7/09（H1N1）样病毒、A/维多利亚/210/2009（H3N2）病毒和B/布里斯班/60/2008样病毒各7.5μg），并与4种不同剂量的佐剂LTh(αK)（7.5、15、30或45μg）以及仅含22.5μg流感血凝素抗原的对照疫苗联合使用。疫苗于第0天和第7天经鼻给药。安全性评估持续180天，并评估第0天和第28天的血凝抑制（HI）抗体滴度以及鼻内HA特异性IgA滴度，以确定是否引发免疫反应。
2012年11月至2013年9月，共招募了36名受试者。24名受试者接受了佐剂疫苗，12名受试者接受了对照疫苗。最常见的不良事件（AE）是轻度鼻不适，全身性不良事件为轻度疲劳和头痛。仅有两名受试者因不良事件退出研究（一名出现3级发热，一名出现结性心律失常）。在含有45μg LTh(αK)的组中，A/H3N2、A/H1N1和B型裂解株的血清保护率分别为100%、100%和80%，鼻内IgA转换因子分别为7.90、7.46和12.27。佐剂LTh(αK)疫苗在B型裂解株特异性IgA的黏膜免疫方面显示出显著增强。
鼻内灭活流感疫苗总体安全，且LTh(αK)佐剂疫苗比无佐剂对照疫苗更具免疫原性。ClinicalTrials.gov标识符：NCT03293732。
