Safety and effectiveness assessment of 2011–2012 seasonal influenza vaccine produced in China: a randomized trial

ABSTRACT

Objective: This study evaluated the effectiveness and safety of the egg-based, trivalent, inactivated split influenza vaccine produced by the Institute of Medical Biology, Chinese Academy of Medical Sciences, Peking Union Medical College, China.

Methods: From March 2012 through May 2012, we enrolled a total of 1390 healthy volunteers between the ages of 3 and 80 years in a randomized clinical trial at the Hebei Disease Control Center Vaccine Clinical Evaluation Center. For all subjects, body part adverse reactions and whole-body adverse reactions were observed 30 min, 6 h, and 1–7 days’ post-inoculation. If no severe adverse effects were observed 7 days’ post-vaccination, the local and systemic reactions of preliminary test participants were recorded until day 28. There was no placebo group in this study. Blood samples were taken for serological testing before vaccination and 28 days’ post-vaccination.

Results: Twenty-eight days after vaccination, the seroconversion rates of experimental and control groups were H1N1 75.3% and 75.7%, H3N2 75.8% and 71.8%, B 70.7% vs. 69.4%, (P > 0.05). The antibody Geometric Mean Titer（GMT）of experimental and control groups were H1N1 (179.7, 182.4), H3N2 (584.0, 445.7), B (201.4,191.6). The protection rate of experimental and control groups was not statistically significant (H1N1: 86% vs. 87%, H3N2: 99% vs. 98%, B: 98% vs. 98%). Also, 95% confidence intervals of the protection rate difference between the experimental and the control group were H1N1: −0.1% (−4.1,3.8) %, H3N2: 0.3% (−1.0,1.7) % and B: 0.2% (−1.5,1.9) %; confidence intervals exceeded the limit of −5%. The rates of adverse reactions between experimental and control groups were 6.3% and 7.7% in local response reactions, and 19.5% and 18.0% in systemic reactions. Three hundred and twenty-seven adverse events (AEs) in 1200 (27.76%) subjects were reported within 28 d after vaccination. No serious adverse events occurred during the study.

Conclusions: The experimental vaccine three-antibody protection rate was non-inferior to the control vaccine. Our results demonstrated that the experimental vaccine achieved the primary immunogenic end point of the intended clinical protocol, as well as a secondary immunogenic end-point, with an acceptable level of safety. IRB approval for this study was issued under #2012Y0005 and registered as Clinical Trial No. NCT01551810.

KEYWORDS:

• Safety
• effectiveness
• seasonal influenza vaccine
• randomized clinical trial
• geometric mean titer
• seroconversion
• Chinese new production

Acknowledgments

We gratefully acknowledge the study participants who volunteered their time and effort. We thank the vaccine clinical evaluation center of Hebei Province Center for Disease Prevention and Control and Dingxing Center for Disease Prevention and Control for their contribution to the study. Many thanks also go to Shanghai Clinical Research Center (Supervision Company, Shanghai, China) for their collected data and input on data management. We are grateful to Shanghai Sunlion medicine science and Technology Co Ltd. (Analysis Company, Shanghai, China). They held and analyzed data. We also would like to thank the National Institutes for Food and Drug Control.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This study was supported by a grant from the Project: Selection Influenza Virus Cold Adapted Strain in Vero Cell, and Study on the Gene Loci Related Low Temperature Adaptation (Grant No. 2010CD134), Cells of Influenza Virus Attenuated Vaccine (Grant No. 2011DFR30420), Research on Genes Related to Adaptation of Influenza Virus in Vero Cell (Grant No. 2013FZ141), The Key Technology and Product Development of Vero Cells Pandemic Influenza Vaccine (Grant No. 2012AA02A404-7), Vero Cells of Influenza Virus Attenuated Vaccine Development (Grant No. 2013ZX10004003-003-002) and Research on the key technology of influenza virus vaccine demonstration and Industrialization (Grant No. 2014AE008). Medical Science and Technology Innovation Project of Chinese Academy of Medical Sciences (Grant No. 2016-I2M-1-019).