Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine (CoronaVac) in healthy children and adolescents: a double-blind, randomised, controlled, phase 1/2 clinical trial

Abstract

Background A vaccine against SARS-CoV-2 for children and adolescents will play an important role in curbing the COVID-19 pandemic. Here we aimed to assess the safety, tolerability, and immunogenicity of a candidate COVID-19 vaccine, CoronaVac, containing inactivated SARS-CoV-2, in children and adolescents aged 3–17 years. Methods We did a double-blind, randomised, controlled, phase 1/2 clinical trial of CoronaVac in healthy children and adolescents aged 3–17 years old at Hebei Provincial Center for Disease Control and Prevention in Zanhuang (Hebei, China). Individuals with SARS-CoV-2 exposure or infection history were excluded. Vaccine (in 0·5 mL aluminum hydroxide adjuvant) or aluminum hydroxide only (alum only, control) was given by intramuscular injection in two doses (day 0 and day 28). We did a phase 1 trial in 72 participants with an age de-escalation in three groups and dose-escalation in two blocks (1·5 μg or 3·0 μg per injection). Within each block, participants were randomly assigned (3:1) by means of block randomisation to receive CoronaVac or alum only. In phase 2, participants were randomly assigned (2:2:1) by means of block randomisation to receive either CoronaVac at 1·5 μg or 3·0 μg per dose, or alum only. All participants, investigators, and laboratory staff were masked to group allocation. The primary safety endpoint was adverse reactions within 28 days after each injection in all participants who received at least one dose. The primary immunogenicity endpoint assessed in the per-protocol population was seroconversion rate of neutralising antibody to live SARS-CoV-2 at 28 days after the second injection. This study is ongoing and is registered with ClinicalTrials.gov , NCT04551547 . Findings Between Oct 31, 2020, and Dec 2, 2020, 72 participants were enrolled in phase 1, and between Dec 12, 2020, and Dec 30, 2020, 480 participants were enrolled in phase 2. 550 participants received at least one dose of vaccine or alum only (n=71 for phase 1 and n=479 for phase 2; safety population). In the combined safety profile of phase 1 and phase 2, any adverse reactions within 28 days after injection occurred in 56 (26%) of 219 participants in the 1·5 μg group, 63 (29%) of 217 in the 3·0 μg group, and 27 (24%) of 114 in the alum-only group, without significant difference (p=0·55). Most adverse reactions were mild and moderate in severity. Injection site pain was the most frequently reported event (73 [13%] of 550 participants), occurring in 36 (16%) of 219 participants in the 1·5 μg group, 35 (16%) of 217 in the 3·0 μg group, and two (2%) in the alum-only group. As of June 12, 2021, only one serious adverse event of pneumonia has been reported in the alum-only group, which was considered unrelated to vaccination. In phase 1, seroconversion of neutralising antibody after the second dose was observed in 27 of 27 participants (100·0% [95% CI 87·2–100·0]) in the 1·5 μg group and 26 ...

Cutaneous and hypersensitivity reactions associated with COVID-19 vaccination—a narrative review

“…Hypersensitivity reactions were not documented [ 12 ]. In phase I and II trials with ZF2001, injection site pain, swelling, and redness was observed in 4–8% for two doses and in up to 14% for three vaccination doses [ 13 ]. In a Sputnik V phase I/II trial, local itching and pain at the injection site and hives in a single patient were reported, but no delayed hypersensitivity reactions [ 14 ].…”

The impacts of Chinese drug volume-based procurement policy on the use of policy-related antibiotic drugs in Shenzhen, 2018–2019: an interrupted time-series analysis

“…The overuse and misuse of antibiotics stimulated the more rapid emergence of antibiotic resistant bacteria and antibiotic resistant genes, reducing their therapeutic potential against human and animal pathogens [ 1 , 2 ]. The rising of antibiotic resistant levels, in combination with a lack of new effective antibiotics, increases the morbidity and mortality of infectious diseases, as well as driving inflation related to healthcare costs [ 3 ].…”

Anti-COVID-19 Vaccination in Patients with Autoimmune-Autoinflammatory Disorders and Primary/Secondary Immunodeficiencies: The Position of the Task Force on Behalf of the Italian Immunological Societies

“…The inactivated traditional vaccine from Sinovac seems to be well tolerated and quite immunogenic [31], even in children and adolescents 3-17 years old, as observed in a phase 1/2 study [32], and an efficacy of 83.5% was just reported [33]. Another inactivated vaccine with an adjuvant, BBV152, is approved in India [18].…”

“…In general, inactivated vaccines or vaccines containing non-infectious viral sequences may be safely administered to patients with AIAIDs, PIDs, and SIDs in clinical remission [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15] (Tables 1-3). Anti-COVID-19 vaccines of the traditional type that are composed by inactivated virus [31][32][33] or recombinant Spike protein and adjuvant [19], for which wider scientific knowledge and clinical experience are available, could preferentially be indicated in patients with AIAIDs, PIDs, and SIDs; however, no traditional vaccines are approved by the European Medicines Agency (EMA) yet (Table 4).…”