A Randomized, Double-Blind, Controlled Phase III Clinical Trial to Evaluate the Immunogenicity and Safety of a Lyophilized Human Rabies Vaccine (Vero Cells) in Healthy Participants Aged 10–60 Years Following Essen and Zagreb Vaccination Procedures
Open accessAbstract
Objective: In this paper, we aim to show that the immunogenicity of the lyophilized human rabies vaccine (Vero cells) (investigational vaccine) developed by Dalian Aleph Biomedical Co., Ltd. in healthy participants aged 10–60 years old is non-inferior to the lyophilized PVRV (positive control) manufactured by Liaoning Chengda Biotechnology Co., Ltd. (Shenyang, China), and that its safety is clinically acceptable. Method: A total of 2776 participants were enrolled in this study and divided into four groups: a five-dose test group, a five-dose control group, a four-dose test group, and a four-dose control group. The patients in the four-dose groups (Zagreb) were vaccinated on Days 0 (two doses), 7 (one dose), and 21 (one dose), and those in the five-dose groups (Essen) were vaccinated on Days 0, 3, 7, 14, and 28 (one dose each). The rabies-virus-neutralizing antibody assay with the RFFIT was used to assess the immunogenicity, and the adverse events (AEs) and serious adverse events (SAEs) were identified and collated. Results: The positive seroconversion rate was up to 100% on Days 14 and 35/42 after vaccination following any procedures in pre-immunization antibody-negative participants, and the positive seroconversion rate and geometric mean concentration (GMC) of the test groups (Zagreb and Essen vaccination procedures) was not inferior to that of the control groups. On Day 7 after vaccination, the immunogenicity of the Zagreb procedure with two doses of the vaccine on Day 0 was superior to the Essen procedure with one dose of vaccine, that is, the former had a higher seroconversion rate and RVNA titer. The non-inferiority criterion of immunogenicity was met for the whole population, the population aged 10–18 years and ≥18 years, and the pre-immunization antibody-positive population. The incidences of all AEs, solicited AEs, and unsolicited AEs in both groups were not statistically significant, and no vaccination-related SAEs were observed. Conclusion: The investigated vaccine is safe, its immunogenicity is non-inferior to that of the control vaccine, and the efficacy of the Zagreb procedure is superior to that of the Essen procedure 7 days after the first dose.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Longitudinal clinical data revealed that the CTN-1 vaccine is safe and effective, making it suitable for rabies prevention and control in China.
“longitudinal clinical data revealed that the vaccine is safe and effective, making it suitable for rabies prevention and control in China [18,21,22,23].”
From Evaluation of the Efficacy of the Vaccine Production Process in Removing Residual Host Cell DNA from the Vero Cell Rabies Vaccine (2024) · cites this paper as [23]
The Investigational Vaccine section identifies the vaccine as containing the CTN-1V strain. The Conclusions (page unavailable) report that it was safe and had good immunogenicity, calling it a valuable alternative for rabies prevention. The study measured immunogenicity and safety in healthy participants, however, not clinical effectiveness in preventing rabies; that stronger part of the claim is not established. (LLM, conf=0.84)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
No citation lists for this paper
No citation lists for this paper yet — checked again daily.
References 21 · Cited by 4
Research works printed but not linked: 21
- [4]Koprowski H. Rabies in the face of the 21st century Zoonoses Public Health 2009 56 258 261 10.1111/j.1863-2378.2009.01266.x 19486313 · DOI
- [5]Pantha S. Subedi D. Poudel U. Subedi S. Kaphle K. Dhakal S. Review of rabies in Nepal One Health 2020 10 100155 10.1016/j.onehlt.2020.100155 33117872 PMC7582201 · DOI
- [7]Rupprecht C. Kuzmin I. Meslin F. Lyssaviruses and rabies: Current conundrums, concerns, contradictions and controversies F1000 Res. 2017 6 184 10.12688/f1000research.10416.1 28299201 PMC5325067 · DOI
- [8]Liu Z. Liu M. Tao X. Zhu W. Epidemic Characteristics of Human Rabies—China, 2016–2020 China CDC Wkly. 2021 3 819 821 10.46234/ccdcw2021.203 34594999 PMC8477051 · DOI
- [9]Moulenat T. Petit C. Bosch Castells V. Houillon G. Purified Vero Cell Rabies Vaccine (PVRV, Verorab®): A Systematic Review of Intradermal Use Between 1985 and 2019 Trop. Med. Infect. Dis. 2020 5 40 10.3390/tropicalmed5010040 32156005 PMC7157209 · DOI
- [10]Costa W.A. Cunha R.S. Bolzan V.L. Silva Ade C. Caporale G.M. Chaves L.B. Oselka G.W. Junqueira D.A. Panacho M.R. Dias R.A. Immunogenicity and safety of a new Vero cell rabies vaccine produced using serum-free medium Vaccine 2007 25 8140 8145 10.1016/j.vaccine.2007.09.043 18029066 · DOI
- [11]Wang C. Zhang X. Song Q. Tang K. Promising rabies vaccine for postexposure prophylaxis in developing countries, a purified vero cell vaccine produced in China Clin. Vaccine Immunol. 2010 17 688 690 10.1128/CVI.00433-09 20147495 PMC2849343 · DOI
- [12]Kalimuddin S. Wijaya L. Chan Y.F.Z. Wong A.W.L. Oh H.M.L. Wang L.F. Kassim J.A. Zhao J. Shi Z. Low J.G. A phase II randomized study to determine the safety and immunogenicity of the novel PIKA rabies vaccine containing the PIKA adjuvant using an accelerated regimen Vaccine 2017 35 7127 7132 10.1016/j.vaccine.2017.10.097 29174316 · DOI
- [13]Rupprecht C.E. Briggs D. Brown C.M. Franka R. Katz S.L. Kerr H.D. Lett S.M. Levis R. Meltzer M.I. Schaffner W. Centers for Disease Control and Prevention (CDC). Use of a reduced (4-dose) vaccine schedule for postexposure prophylaxis to prevent human rabies: Recommendations of the advisory committee on immunization practices MMWR Recomm. Rep. 2010, 59, 1–9; Erratum in MMWR Recomm. Rep. 2010 59 493 20300058
- [14]World Health Organization Rabies vaccines: WHO position paper, April 2018—Recommendations Vaccine 2018 36 5500 5503 10.1016/j.vaccine.2018.06.061 30107991 · DOI
- [15]Zhang L. Huang S. Cai L. Zhu Z. Chen J. Lu S. Zhu Z. Zhang M. Fang Y. Hu Q. Safety, immunogenicity of lyophilized purified vero cell cultured rabies vaccine administered in Zagreb and Essen regimen in post-exposure participants: A post-marketing, parallel control clinical trial Hum. Vaccine Immunother. 2021 17 2547 2553 10.1080/21645515.2021.1880200 33631078 PMC8475608 · DOI
- [16]Ren J. Yao L. Sun J. Gong Z. Zagreb regimen, an abbreviated intramuscular schedule for rabies vaccination Clin. Vaccine Immunol. 2015 22 1 5 10.1128/CVI.00531-14 25392012 PMC4278924 · DOI
- [17]Liu H. Huang G. Tang Q. Li J. Cao S. Fu C. Cao Q. Liu B. Pan H. Wang M. The immunogenicity and safety of vaccination with purified Vero cell rabies vaccine (PVRV) in China under a 2-1-1 regimen Hum. Vaccine 2011 7 220 224 10.4161/hv.7.2.14003 21311216 · DOI
- [18]Hu Q. Liu M.Q. Zhu Z.G. Zhu Z.R. Lu S. Comparison of safety and immunogenicity of purified chick embryo cell vaccine using Zagreb and Essen regimens in patients with category II exposure in China Hum. Vaccines Immunother. 2014 10 1645 1649 10.4161/hv.28420 24632727 PMC5396232 · DOI
- [19]Scheiermann N. Baer J. Hilfenhaus J. Marcus I. Zoulek G. Reactogenicity and immunogenicity of the newly developed purified chick embryo cell (PCEC)-rabies vaccine in man Zentralblatt für Bakteriologie, Mikrobiologie und Hygiene. Ser. A: Med. Microbiol. Infect. Dis. Virol. Parasitol. 1987 265 439 450 10.1016/S0176-6724(87)80263-8 2445127 · DOI
- [20]Shen H. Wang Z. Yang B. Cai K. Jiang C. Xie R. Xiao H. Ren Q. Qi Z. Li J. Immunogenicity and safety of purified vero cell-cultured rabies vaccine under Zagreb 2-1-1 or 5-dose Essen regimen in the healthy Chinese participants: A randomized, double-blind, positive controlled phase 3 clinical trial Hum. Vaccine Immunother. 2021 17 351 357 10.1080/21645515.2020.1778408 PMC7899666 32783769 · DOI
- [21]Li R. Huang L. Li J. Mo Z. He B. Wang Y. Wu X. Minutello M. Guinet-Morlot F. Pichon S. A next-generation, serum-free, highly purified Vero cell rabies vaccine is safe and as immunogenic as the reference vaccine Verorab® when administered according to a post-exposure regimen in healthy children and adults in China Vaccine 2013 31 5940 5947 10.1016/j.vaccine.2013.10.043 24148575 · DOI
- [22]Fang Y. Liu M.Q. Chen L. Zhu Z.G. Zhu Z.R. Hu Q. Rabies post-exposure prophylaxis for a child with severe allergic reaction to rabies vaccine Hum. Vaccine Immunother. 2016 12 1802 1804 10.1080/21645515.2016.1143158 PMC4964825 26900624 · DOI
- [23]Wang J. Luo F. Feng Z. Li L. Bai Y. Ai X. Ma J. Zhang Z. Shi N. Immunogenicity and safety of purified vero cell rabies vaccine (PVRV) produced by Liaoning Cheng Da Co. under Zagreb 2-1-1 or 5-dose Essen regimen in Chinese adults aged 50 and above Hum. Vaccine Immunother. 2017 13 144 150 10.1080/21645515.2016.1230260 PMC5287299 28045585 · DOI
- [24]Pichon S. Moureau A. Petit C. Chu L. Essink B. Muse D. Saleh J. Guinet-Morlot F. Minutello A.M. Safety and immunogenicity of a serum-free purified Vero rabies vaccine in healthy adults: A randomised phase II pre-exposure prophylaxis study Vaccine 2022 40 4780 4787 10.1016/j.vaccine.2022.06.040 35778281 · DOI
- [25]Peng J. Chen L. Zhu Z.G. Zhu Z.R. Hu Q. Fang Y. Effect of Corticosteroids on RVNA production of a patient with acute disseminated encephalomyelitis following rabies vaccination as well as administration of HRIG Hum. Vaccine Immunother. 2014 10 3622 3626 10.4161/21645515.2014.979621 25668669 PMC4514047 · DOI
- Authors
- Wu, X., Li, J., Zhou, L., Chen, J., Jin, Z., Meng, Q., Chai, J., Gao, H., Wang, Y., Zhao, D., Wu, H., Yu, J., Chen, N., Wang, Y., Lin, Y., Huang, P., Li, Y., & Zhang, Y.
- Affiliations
- National Institutes for Food and Drug Control (CN)
- Dalian University of Technology (CN)
- General Manager Office, Dalian Aleph Biomedical Co., Ltd., Dalian 116620, China
- Sichuan Center for Disease Control and Prevention (CN)
- Quality Control Department, Dalian Aleph Biomedical Co., Ltd., Dalian 116620, China
- Rabies Vaccine Production Workshop, Dalian Aleph Biomedical Co., Ltd., Dalian 116620, China
- Filling and Packaging Workshop, Dalian Aleph Biomedical Co., Ltd., Dalian 116620, China
- Department of Scientific Affairs, Simoon Record Beijing Co., Ltd., Beijing 100025, China
- Department of Project Management, Simoon Record Beijing Co., Ltd., Beijing 100025, China
- Corresponding author
- Li, Yuhua
- Zhang, Yuhui
- ORCID
- Venue
- Vaccines
- Publisher
- MDPI AG
- Published
- 2023-08-01
- Volume
- 11
- Issue
- 8
- Pages
- 1311
- ISSN
- 2076-393X (ISSN-L)
- PMC
- PMC10458047
- OpenAlex
- W4385446586
- Cited by
- 4
- References
- 21
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2
- FWCI
- 0.53
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Vaccines (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Dalian Aleph Biomedical Co., Ltd.
- Topics
- Life Sciences › Immunology and Microbiology › Virology › Rabies epidemiology and control
- Health Sciences › Medicine › Epidemiology › Virology and Viral Diseases
- Life Sciences › Immunology and Microbiology › Microbiology › Bacterial Infections and Vaccines
- Keywords
- rabies vaccine, Vero cell rabies vaccine, lyophilized vaccine, immunogenicity, vaccine safety, non-inferiority, seroconversion, rabies virus neutralizing antibodies, vaccination schedule, adverse events
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
