van Dissel Jaap T, Joosten Simone A, Hoff Søren T, Soonawala Darius, Prins Corine, Hokey David A, O'Dee Dawn M, Graves Andrew, Thierry-Carstensen Birgit, Andreasen Lars V, Ruhwald Morten, de Visser Adriëtte W, Agger Else Marie, Ottenhoff Tom H M, Kromann Ingrid, Andersen Peter
Leiden University Medical Center (LUMC), Department of Infectious Diseases, Leiden, The Netherlands.
Leiden University Medical Center (LUMC), Department of Infectious Diseases, Leiden, The Netherlands.
Vaccine. 2014 Dec 12;32(52):7098-107. doi: 10.1016/j.vaccine.2014.10.036. Epub 2014 Oct 30.
Here, we report on a first-in-man trial where the tuberculosis (TB) vaccine Ag85B-ESAT-6 (H1) was adjuvanted with escalating doses of a novel liposome adjuvant CAF01. On their own, protein antigens cannot sufficiently induce immune responses in humans, and require the addition of an adjuvant system to ensure appropriate delivery and concomitant immune activation. To date no approved adjuvants are available for induction of cellular immunity, which seems essential for a number of vaccines, including vaccines against TB. We vaccinated four groups of human volunteers: a non-adjuvanted H1 group, followed by three groups with escalating doses of CAF01-adjuvanted H1 vaccine. All subjects were vaccinated at 0 and 8 weeks and followed up for 150 weeks. Vaccination did not cause local or systemic adverse effects besides transient soreness at the injection site. Two vaccinations elicited strong antigen-specific T-cell responses which persisted after 150 weeks follow-up, indicating the induction of a long-lasting memory response in the vaccine recipients. These results show that CAF01 is a safe and tolerable, Th1-inducing adjuvant for human TB vaccination trials and for vaccination studies in general where cellular immunity is required.
在此，我们报告了一项首例人体试验，其中结核病（TB）疫苗Ag85B - ESAT - 6（H1）与新型脂质体佐剂CAF01的递增剂量联合使用。蛋白质抗原自身无法在人体中充分诱导免疫反应，需要添加佐剂系统以确保适当的递送和伴随的免疫激活。迄今为止，尚无获批用于诱导细胞免疫的佐剂，而细胞免疫对于包括结核病疫苗在内的多种疫苗似乎至关重要。我们对四组人类志愿者进行了接种：一组为未添加佐剂的H1组，随后是三组接种递增剂量CAF01佐剂H1疫苗的组。所有受试者均在第0周和第8周进行接种，并随访150周。除注射部位出现短暂疼痛外，接种未引起局部或全身不良反应。两次接种引发了强烈的抗原特异性T细胞反应，这些反应在随访150周后依然持续，表明在疫苗接种者中诱导出了持久的记忆反应。这些结果表明，CAF01是一种安全且可耐受的、诱导Th1的佐剂，可用于人体结核病疫苗试验以及一般需要细胞免疫的疫苗研究。
