Wijaya Limin, Tham Christine Y L, Chan Yvonne F Z, Wong Abigail W L, Li L T, Wang Lin-Fa, Bertoletti Antonio, Low Jenny G
Department of Infectious Diseases, Singapore General Hospital, 20 College Road, Singapore 169856, Singapore.
Singapore Institute for Clinical Sciences, Agency for Science Technology and Research (A*STAR), 30 Medical Drive, Singapore 117609, Singapore; NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, 28 Medical Drive, Singapore 117456, Singapore.
Vaccine. 2017 Feb 22;35(8):1175-1183. doi: 10.1016/j.vaccine.2016.12.031. Epub 2017 Jan 22.
Rabies is a fatal disease where post-exposure prophylaxis (PEP) is crucial in preventing infection. However, deaths even after appropriate PEP, have been reported. The PIKA Rabies vaccine adjuvant is a TLR3 agonist that activates B and T cells leading to a robust immune response.
We conducted a phase I, open label, randomized study in healthy adults to assess the safety and immunogenicity of the PIKA Rabies vaccine and an accelerated vaccine regimen. Thirty-seven subjects were randomized into 3 groups: control vaccine classic regimen, PIKA vaccine classic regimen and PIKA vaccine accelerated regimen. Subjects were followed up for safety, rabies virus neutralizing antibodies (RVNA) and T cell responses.
Both the control and PIKA Rabies vaccine were well tolerated. All adverse events (AEs) were mild and self-limiting. Seventy-five percent of subjects in the PIKA accelerated regimen achieved a RVNA titer ⩾0.5IU/mL on day 7, compared to 53.9% in the PIKA classic regimen (p=0.411) and 16.7% in control vaccine classic regimen (p=0.012). The PIKA rabies vaccine elicited multi-specific rabies CD4 mediated T cell response already detectable ex vivo at day 7 after vaccination and that was maintained at day 42.
The investigational PIKA rabies vaccine was well tolerated and more immunogenic than the commercially available vaccine in healthy adults. Clinical trial registry: The study was registered with clinicaltrials.gov NCT02657161.
狂犬病是一种致命疾病，暴露后预防（PEP）对于预防感染至关重要。然而，即使进行了适当的PEP后仍有死亡报告。PIKA狂犬病疫苗佐剂是一种TLR3激动剂，可激活B细胞和T细胞，引发强烈的免疫反应。
我们在健康成年人中进行了一项I期开放标签随机研究，以评估PIKA狂犬病疫苗和加速疫苗接种方案的安全性和免疫原性。37名受试者被随机分为3组：对照疫苗经典方案组、PIKA疫苗经典方案组和PIKA疫苗加速方案组。对受试者进行安全性、狂犬病病毒中和抗体（RVNA）和T细胞反应的随访。
对照疫苗和PIKA狂犬病疫苗耐受性均良好。所有不良事件（AE）均为轻度且自限性。PIKA加速方案组75%的受试者在第7天RVNA滴度达到⩾0.5IU/mL，相比之下，PIKA经典方案组为53.9%（p=0.411），对照疫苗经典方案组为16.7%（p=0.012）。PIKA狂犬病疫苗在接种后第7天可在体外检测到引发多特异性狂犬病CD4介导的T细胞反应，并在第42天维持。
在健康成年人中，研究性PIKA狂犬病疫苗耐受性良好，且比市售疫苗更具免疫原性。临床试验注册：该研究已在clinicaltrials.gov上注册，注册号为NCT02657161。
