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Vaccine. 2017 Feb 22;35(8):1175-1183. doi: 10.1016/j.vaccine.2016.12.031. Epub 2017 Jan 22.

An accelerated rabies vaccine schedule based on toll-like receptor 3 (TLR3) agonist PIKA adjuvant augments rabies virus specific antibody and T cell response in healthy adult volunteers.

Author information

1
Department of Infectious Diseases, Singapore General Hospital, 20 College Road, Singapore 169856, Singapore. Electronic address: limin.wijaya@singhealth.com.sg.
2
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. Electronic address: ylin@duke-nus.edu.sg.
3
Department of Infectious Diseases, Singapore General Hospital, 20 College Road, Singapore 169856, Singapore. Electronic address: yvonne.chan2@mohh.com.sg.
4
Department of Infectious Diseases, Singapore General Hospital, 20 College Road, Singapore 169856, Singapore. Electronic address: abigail.wong.w.l@sgh.com.sg.
5
Yisheng Biopharma (Singapore) Pte. Ltd., 20 Maxwell Road, Maxwell House 07-15A, Singapore 069113, Singapore. Electronic address: lietao.li@gmail.com.
6
Program in Emerging Infectious Diseases, DUKE-NUS Medical School, 8 College Road, Singapore 169857, Singapore. Electronic address: linfa.wang@duke-nus.edu.sg.
7
Program in Emerging Infectious Diseases, DUKE-NUS Medical School, 8 College Road, Singapore 169857, Singapore; Singapore Institute for Clinical Sciences, Agency for Science Technology and Research (A*STAR), 30 Medical Drive, Singapore 117609, Singapore. Electronic address: antonio@duke-nus.edu.sg.
8
Department of Infectious Diseases, Singapore General Hospital, 20 College Road, Singapore 169856, Singapore. Electronic address: jenny.low@singhealth.com.sg.

Abstract

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSION:

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.

KEYWORDS:

Immunogenicity; PIKA rabies vaccine; Rabies-specific T cell immune response; Safety

PMID:
28118938
DOI:
10.1016/j.vaccine.2016.12.031
[Indexed for MEDLINE]

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