Safety and reactogenicity of the adjuvanted recombinant zoster vaccine: experience from clinical trials and post-marketing surveillance

Abstract

An adjuvanted recombinant zoster vaccine (RZV) is licensed for the prevention of herpes zoster. This paper reviews its safety and reactogenicity. A pooled analysis of two pivotal randomized Phase-3 trials (NCT01165177, NCT01165229) in adults ⩾50 years found that more solicited adverse events (AEs) were reported with RZV than placebo. Injection site pain was the most common solicited AE (RZV: 78.0% participants; placebo: 10.9%). Grade-3 pain occurred in 6.4% of RZV and 0.3% of placebo recipients. Myalgia, fatigue, and headache were the most commonly reported general solicited AEs (RZV: 44.7%, 44.5%, and 37.7%, respectively; placebo: 11.7%, 16.5%, and 15.5%, respectively). Most symptoms were mild to moderate in intensity with a median duration of 2–3 days. The intensity of reactogenicity symptoms did not differ substantially after the first and second vaccine doses. The pooled analysis of the pivotal Phase-3 trials did not identify any clinically relevant differences in the overall incidence of serious adverse events (SAEs), fatal AEs or potential immune-mediated diseases (pIMDs) between RZV and placebo. Reactogenicity in five studies of immunocompromised patients ⩾18 years (autologous stem cell transplant, human immunodeficiency virus, solid tumors, hematological malignancies, and renal transplant; NCT01610414, NCT01165203, NCT01798056, NCT01767467, and NCT02058589) was consistent with that observed in the pivotal Phase-3 trials. There were no clinically relevant differences between RZV and placebo in the immunocompromised populations with regard to overall incidence of SAEs, fatal AEs, pIMDs, or AEs related to patients’ underlying condition. Post-marketing surveillance found that the most commonly reported AEs were consistent with the reactogenicity profile of the vaccine in clinical trials. Overall, the clinical safety data for RZV are reassuring. [Formula: see text]

Herpes zoster mRNA vaccine induces superior vaccine immunity over licensed vaccine in mice and rhesus macaques

“…Considering that aged individuals are main target population of zoster vaccine and these cohorts are more susceptible to cardiovascular diseases, the inappropriate platelet activation induced by Shingrix may pose a potential risk. Besides, the increased expression of pain-related genes also supported the clinical findings that local injection site pain is the most common solicited adverse event in Shingrix recipients [36]. In addition, it should be noted that our mRNA vaccine encodes full-length gE, which is in contrast with Shingrix that contains truncated form of gE (1-544 aa) [55].…”

“…A promising vaccine candidate should possess a high safety profile. Despite the fact that Shingrix is highly effective to prevent zoster, clinical trials and post-marketing surveillance have reported a high local and systemic reactogenicity of Shingrix [36]. In this study, we preliminarily evaluated safety properties of ZOSAL by monitoring levels of various serum biochemical parameters following vaccination, including liver and kidney enzymes.…”

Herpes zoster mRNA vaccine induces superior vaccine immunity over licensed vaccine in mice and rhesus macaques

“…Considering that aged individuals are the main target population of the zoster vaccine and these cohorts are more susceptible to cardiovascular diseases, the inappropriate platelet activation induced by Shingrix may pose a potential risk. Besides, the increased expression of pain-related genes also supported the clinical findings that local injection site pain is the most common solicited adverse event in Shingrix recipients [ 36 ]. In addition, it should be noted that our mRNA vaccine encodes full-length gE, which is in contrast with Shingrix that contains a truncated form of gE (1-544 aa) [ 55 ].…”

“…A promising vaccine candidate should possess a high safety profile. Despite the fact that Shingrix is highly effective in preventing zoster, clinical trials, and post-marketing surveillance have reported a high local and systemic reactogenicity of Shingrix [ 36 ]. In this study, we preliminarily evaluated the safety properties of ZOSAL by monitoring levels of various serum biochemical parameters following vaccination, including liver and kidney enzymes.…”

Establishment of Safety Monitoring System for Vaccines Not Included in the National Immunization Program in Korea

“…Despite the difficulty of operation and the similarity in the pattern of early adverse events between the present study and the existing literature, this monitoring approach should be maintained due to the significant time lag associated with the methods described later, especially in the event of unexpected AESI occurrences. 17 18 19 20 21 22 23 24 25 26 27 Second, retrospective screening was not efficient based on the scale of efforts, and the number of participants included in this study was too small to observe rare AESI cases. Moreover, the rate of AESI may have been underestimated.…”