Meta-analysis of immunogenicity and safety of human rabies vaccination under Zagreb and Essen regimens
Publication: Journal of Comparative Effectiveness Research
Abstract
Aim: To assess the immunogenicity and safety of rabies vaccination under the Zagreb and Essen regimens by performing a meta-analysis. Methods: Electronic databases were searched for eligible studies. Risk ratios and weighted mean differences with 95% CIs were used to calculate estimates. Results: A total of 18 studies were included. Rabies virus neutralizing antibody concentration was comparable between the two regimens at D7 and 14. No significant differences were observed in seroconversion rates from D14 and 42. Incidence of fever was higher in Zagreb group (risk ratio: 1.55 [1.37–1.76]); but no significant differences were present for other common adverse events. Conclusion: Rabies vaccination under the Zagreb regimen was noninferior to the Essen regimen in immunogenicity and had an acceptable safety profile.
Formats available
You can view the full content in the following formats:
References
Papers of special note have been highlighted as: • of interest
1.
Hemachudha T, Wacharapluesadee S, Mitrabhakdi E, Wilde H, Morimoto K, Lewis RA. Pathophysiology of human paralytic rabies. J. Neurovirol. 11(1), 93–100 (2005).
2.
McGettigan JP. Experimental rabies vaccines for humans. Expert Rev. Vaccines 9, 1177–1186 (2010).
3.
Nandi S, Kumar M. Development in immunoprophylaxis against rabies for animals and humans. AJMB 2, 3–21 (2010).
4.
WHO. WHO Expert consultation on rabies: first report. World Health Organ. Tech. Rep. Ser. 931, 1–88 (2005).
5.
Rupprecht CE, Briggs D, Brown CM et al. 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. 59(RR-2), 1–9 (2010).
6.
Liu H, Huang G, Tang Q et al. The immunogenicity and safety of vaccination with purified Vero cell rabies vaccine (PVRV) in China under a 2-1-1 regimen. Hum. Vaccin. 7(2), 220–224 (2011).
• A relatively high-quality clinical trial used for this meta-analysis.
7.
Rahimi P, Vahabpour R, Shirzadi MR, Bahramali G, Aghasadeghi MR. Rabies prophylaxis strategy in Iran, a need for an alternative strategy: would the Essen regimen be replaced by Zagreb protocol? Clin. Lab. 65(1), 10.7754 (2019).
8.
Fang Y, Chen L, Liu MQ, Zhu ZG, Zhu ZR, Hu Q. Comparison of safety and immunogenicity of PVRV and PCECV immunized in patients with WHO category II animal exposure: a study based on different age groups. PLoS Negl. Trop. Dis. 8(12), e3412 (2014).
• A relatively high-quality clinical trial used for this meta-analysis.
9.
Li R, Li Y, Wen S et al. Immunogenicity and safety of purified chickembryo cell rabies vaccine under Zagreb 2-1-1 or 5-dose Essen regimen in Chinese children 6 to 17 years old and adults over 50 years: a randomized open-label study. Hum. Vaccin. Immunother. 11(2), 435–442 (2015).
• A relatively high-quality clinical trial used for this meta-analysis.
10.
Higgins J, Green S. Cochrane Handbook for Systematic Reviews of Interventions: Cochrane Book Series. John Wiley & Sons, Ltd, Chichester, UK, 1–649 (2008).
11.
Chen ZQ. Clinical study of rabies vaccine administered with 5-dose immunization program and 2-1-1 immunization program. Med. Aesthe. Cosm. 2, 224 (2015).
12.
Chen ZP, Lv HK, Wang SY, Li YH. Immunogenicity of human diploid cell rabies vaccine vaccinated with Zagreb regimen. Chin. J. Emerg. Resusc. Disaster Med. 13(11), 1069–1071 (2018).
13.
Hu Q, Liu MQ, Zhu ZG, Zhu ZR, 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. Vaccin. Immunother. 10(6), 1645–1649 (2014).
14.
Huang F, Xie L, Yi T. Effect and nursing intervention of “2-1-1” rabies vaccine immunization program and ‘5-dose’ immunization program. Prac. Clin. Med. 15(3), 103–104 (2014).
15.
Ma J, Wang H, Li J et al. A randomized open-labeled study to demonstrate the non-inferiority of purified chick-embryo cell rabies vaccine administered in the Zagreb regimen (2-1-1) compared with the Essen regimen in Chinese adults. Hum. Vaccin. Immunother. 10(10), 2805–2812 (2014).
• A relatively high-quality clinical trial used for this meta-analysis.
16.
Mahendra BJ, Narayana DA, Agarkhedkar S et al. Comparative study on the immunogenicity and safety of a purified chick embryo cell rabies vaccine (PCECV) administered according to two different simulated post exposure intramuscular regimens (Zagreb versus Essen). Hum. Vaccin. Immunother. 11(2), 428–434 (2015).
• A relatively high-quality clinical trial used for this meta-analysis.
17.
Mao R, Jin AB, Cao JS. Comparison of different immunization procedures for rabies exposure prophylaxis. Chin. J. Public Health 29(9), 1403–1404 (2013).
18.
Miao L, Shi L, Yang Y et al. Immunological effect of aGV rabies vaccine administered using the Essen and Zagreb regimens: a double-blind, randomized clinical trial. Viral Immunol. 31(3), 242–248 (2018).
• A relatively high-quality clinical trial used for this meta-analysis.
19.
Sari T, Tulek N, Bulut C, Oral B, Tuncer EG. Adverse events following rabies post-exposure prophylaxis: a comparative study of two different schedules and two vaccines. Travel Med. Infect. Dis. 12, 659–666 (2014).
20.
Shao W, Zheng YS, Zhang J, Jiang YZ, Jiang XY. Observation on efficacy and side effects of “2-1-1” Needle injection rabies vaccine in patients exposed. Chin. J. Gen. Prac. 11(11), 1768–1769 (2013).
21.
Shi N, Zhang Y, Zheng H et al. Immunogenicity, safety and antibody persistence of a purified vero cell cultured rabies vaccine (Speeda) administered by the Zagreb regimen or Essen regimen in post-exposure subjects. Hum. Vaccin. Immunother. 13(6), 1–8 (2017).
• A relatively high-quality clinical trial used for this meta-analysis.
22.
Wang J, Luo F, Feng Z et al. 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. Vaccin. Immunother. 13(1), 144–150 (2017).
• A relatively high-quality clinical trial used for this meta-analysis.
23.
Xie FX, Qiu T. Comparative study of safety of rabies vaccine between 4 and 5 dose immune procedures. J. Prev. Med. Inf. 31(1), 65–68 (2015).
24.
Xie ZW, Chen YN, Liao XW, Wang MC. Safety assessment of different age groups using 2-1-1 vaccination. J. Trop. Med. 16(2), 249–251 (2016).
25.
Ye WM. Comparative analysis on safety of rabies vaccine Phases IV and V immunization for exposed persons. Chin. J. Mod. Drg. Appl. 11(11), 189–191 (2017).
26.
Wang LY, Sun MP, Zhang XC et al. Safety and immunogenicity of two freeze-dried vero cell rabies vaccines for human use in post-exposure prophylaxis. Vaccine 29, 2679–2681 (2011).
27.
Ashwath Narayana DH, Madhusudana SN, Sampath G et al. Safety and immunogenicity study of a new purified chick embryo cell rabies vaccine Vaxirab-N (Pitman-Moore strain) manufactured in India. Hum. Vaccin. Immunother. 10, 120–125 (2014).
28.
WHO Expert Committee on Rabies. World Health Organ. Tech. Rep. Ser. 824, 1–84 (1992).
29.
Scott P, Chanthavanich P, Chen LH et al. Post-exposure prophylaxis (PEP) for rabies with purified chick embryo cell vaccine: a systematic literature review and meta-analysis. Expert Rev. Vaccines 17(6), 525–545 (2018).
30.
Wang CL, Zhang XW, Yu YX. Study on the compliance and economic cost of rabies vaccination. Zhongguo Yi Miao He Mian Yi 16, 254–257 (2010).
Information & Authors
Information
Published In
Pages: 459 - 468
PubMed: 32374178
Copyright
© 2020 Future Medicine Ltd.
History
Received: 23 December 2019
Accepted: 25 February 2020
Published online: 6 May 2020
Keywords:
Topics
Authors
Metrics & Citations
Metrics
Article Usage
Article usage data only available from February 2023. Historical article usage data, showing the number of article downloads, is available upon request.
Citations
How to Cite
Meta-analysis of immunogenicity and safety of human rabies vaccination under Zagreb and Essen regimens. (2020) Journal of Comparative Effectiveness Research. DOI: 10.2217/cer-2019-0202
Export citation
Select the citation format you wish to export for this article or chapter.
Citing Literature
- Hua-Kun Lv, Xu Chen, Bo Xing, Xiao-Song Hu, Xin-Pei Zhang, Yu-Gang Shen, Yan Wang, Miao-Miao Liu, Ying-Ping Chen, Zhen-Zhen Liang, Yu Mao, A phase 3 clinical trial on the immunogenicity and safety of booster vaccination after Zagreb or Essen regimens, Scientific Reports, 10.1038/s41598-025-88361-1, 15, 1, (2025).
- Zhenzhen Liang, Xu Chen, Bo Xing, Xiaosong Hu, Miaomiao Liu, Xinpei Zhang, Yugang Shen, Yan Wang, Yingping Chen, Huakun Lv, Yu Mao, Safety, immunogenicity and immune-persistence of a lyophilized human rabies vaccine (Vero cells) under Zagreb and Essen regimens: a randomized, open-label, controlled phase III clinical trial in healthy participants aged 10–60 years in China, Frontiers in Immunology, 10.3389/fimmu.2024.1444686, 15, (2024).
- Danaya Chansinghakul, Terapong Tantawichien, Kriengsak Limkittikul, Winai Ratanasuwan, Yuancheng Wang, Celine Petit, Francoise Guinet-Morlot, Carina Frago, Andrea-Clemencia Pineda-Peña, Randomized Controlled Trial of the Immunogenicity and Safety of a Serum-Free Purified Vero Rabies Vaccine (PVRV-NG2) Using a Simulated Postexposure Zagreb Regimen With Human Rabies Immunoglobulin in Adults in Thailand, Open Forum Infectious Diseases, 10.1093/ofid/ofae633, 11, 11, (2024).
- Pavle Banović, Dragana Mijatović, Verica Simin, Nenad Vranješ, Eleftherios Meletis, Polychronis Kostoulas, Dasiel Obregon, Alejandro Cabezas-Cruz, Real-world evidence of rabies post-exposure prophylaxis in Serbia: Nation-wide observational study (2017–2019), Travel Medicine and Infectious Disease, 10.1016/j.tmaid.2024.102697, 58, (102697), (2024).
- Ruiqi Lu, Jinsheng Lin, Yang Zhou, Qian Chen, Zaiying Fan, Shuning Wu, Pei Qin, Liping Li, Rabies vaccination adherence and associated factors among rabies-exposed patients in Shenzhen, China: a hospital-based cross-sectional study, Epidemiology and Infection, 10.1017/S0950268824000049, 152, (2024).
- Tianren Shen, Susan Christina Welburn, Long Sun, Guo-Jing Yang, Progress towards dog-mediated rabies elimination in PR China: a scoping review, Infectious Diseases of Poverty, 10.1186/s40249-023-01082-3, 12, 1, (2023).
- Kanika Gupta, Management of Animal Bite, Infections and Pregnancy, 10.1007/978-981-16-7865-3_31, (491-506), (2022).
- Shi-Yuan Wang, Jin-Fang Sun, Pei Liu, Li Luo, Jing-Xin Li, Feng-Cai Zhu, Xu-Xiang Shen, Fan-Yue Meng, Immunogenicity and safety of human diploid cell vaccine (HDCV) vs. purified Vero cell vaccine (PVRV) vs. purified chick embryo cell vaccine (PCECV) used in post-exposure prophylaxis: a systematic review and meta-analysis, Human Vaccines & Immunotherapeutics, 10.1080/21645515.2022.2027714, 18, 1, (2022).
- Tauseef Ahmad, undefined Haroon, Muhammad Khan, Manal Abdulaziz Murad, Mukhtiar Baig, Bibi Nazia Murtaza, Muhammad Mumtaz Khan, Harapan Harapan, Jin Hui, Research trends in rabies vaccine in the last three decades: a bibliometric analysis of global perspective, Human Vaccines & Immunotherapeutics, 10.1080/21645515.2021.1910000, 17, 9, (3169-3177), (2021).