Safety and immunogenicity of an alum-adjuvanted whole-virion H7N9 influenza vaccine: a randomized, blinded, clinical trial

Shilei Wang; Zhiqiang Xie; Lili Huang; Xu Zhou; Jian Luo; Yuelian Yang; Changgui Li; Peng Duan; Wenting Xu; Dandan Chen; Bing Wu; Yongli Yang; Xueying Liu; Yanxia Wang; Zhenghong Yuan; Di Qu; Ze Chen; Shengli Xia

doi:10.1016/j.cmi.2020.07.033

Safety and immunogenicity of an alum-adjuvanted whole-virion H7N9 influenza vaccine: a randomized, blinded, clinical trial

Clin Microbiol Infect. 2020 Jul 29:S1198-743X(20)30441-9. doi: 10.1016/j.cmi.2020.07.033. Online ahead of print.

Authors

Shilei Wang¹, Zhiqiang Xie², Lili Huang², Xu Zhou³, Jian Luo³, Yuelian Yang³, Changgui Li⁴, Peng Duan³, Wenting Xu³, Dandan Chen³, Bing Wu³, Yongli Yang⁵, Xueying Liu³, Yanxia Wang², Zhenghong Yuan⁶, Di Qu⁷, Ze Chen⁸, Shengli Xia⁹

Affiliations

¹ Shanghai Institute of Biological Products, Shanghai, China; Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Shanghai Medical College of Fudan University, Shanghai, China.
² Henan Province Centre for Disease Control and Prevention, Centre of Vaccine Clinical Research, China.
³ Shanghai Institute of Biological Products, Shanghai, China.
⁴ National Institutes for Food and Drug Control, WHO Collaborating Centre for Standardization and Evaluation of Biologicals, Beijing, China.
⁵ Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, 450001, China.
⁶ Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Shanghai Medical College of Fudan University, Shanghai, China.
⁷ Biosafety Level-3 Laboratory, Key Laboratory of Medical Molecular Virology MOE & MOH, School of Basic Medical Sciences, Fudan University, Shanghai, China.
⁸ Shanghai Institute of Biological Products, Shanghai, China. Electronic address: chenze2005@hotmail.com.
⁹ Henan Province Centre for Disease Control and Prevention, Centre of Vaccine Clinical Research, China. Electronic address: 1792865518@qq.com.

PMID: 32738479
DOI: 10.1016/j.cmi.2020.07.033

Abstract

Objectives: A case of H7N9 influenza virus infection was first identified in China in 2013. This virus is considered to have high pandemic potential. Here we developed an H7N9 influenza vaccine containing an aluminium adjuvant and evaluated the safety and immunogenicity of the vaccine.

Methods: From October 2017 through August 2018 we conducted a randomized, double-blinded, single-centre phase I clinical trial in China among 360 participants aged ≥12 years. All participants received two doses of the vaccine (7.5, 15 or 30 μg haemagglutinin antigen) or placebo at an interval of 21 days. Adverse event data were collected for 30 days after vaccination. Serum samples were collected on days 0, 21 and 42 for the haemagglutinin inhibition (HI) antibody assay.

Results: A total of 347 participants (347/360, 96.4%) completed the study. The proportions of vaccine-related adverse events after one injection were 56.7% (34/60) in the 7.5-μg group, 86.7% (52/60) in the 15-μg group and 86.7% (52/60) in the 30-μg group. The proportions of adverse events after two injections were less than those reported after the first dose. None of the serious adverse events were related to the vaccine. After receiving two doses of the 7.5-μg vaccine, the proportion of participants achieving an HI titre of ≥40 was 98.2% (55/56, 95%CI 72.3~100.0%), with a geometric mean titre (GMT) of 192.6 (95%CI 162.9~227.8).

Conclusions: The alum-adjuvanted H7N9 whole-virion inactivated vaccine was safe and strongly immunogenic in a population aged ≥12 years.

Keywords: Alum adjuvant; Clinical trial; H7N9; Immunogenicity; Whole-virion vaccine.