ABSTRACT
BackgroundThe development of vaccines to control the COVID-19 pandemic progression is a worldwide priority. CoronaVac(R) is an inactivated SARS-CoV-2 vaccine approved for emergency use with robust efficacy and immunogenicity data reported in trials in China, Brazil, Indonesia, Turkey, and Chile. MethodsThis study is a randomized, multicenter, and controlled phase 3 trial in healthy Chilean adults aged [≥]18 years. Volunteers received two doses of CoronaVac(R) separated by two (0-14 schedule) or four weeks (0-28 schedule). 2,302 volunteers were enrolled, 440 were part of the immunogenicity arm, and blood samples were obtained at different times. Samples from a single center are reported. Humoral immune responses were evaluated by measuring the neutralizing capacities of circulating antibodies. Cellular immune responses were assessed by ELISPOT and flow cytometry. Correlation matrixes were performed to evaluate correlations in the data measured. ResultsBoth schedules exhibited robust neutralizing capacities with the response induced by the 0-28 schedule being better. No differences were found in the concentration of antibodies against the virus and different variants of concern between schedules. Stimulation of PBMCs with MPs induced the secretion of IFN-{gamma} and the expression of activation induced markers for both schedules. Correlation matrixes showed strong correlations between neutralizing antibodies and IFN-{gamma} secretion. ConclusionsImmunization with CoronaVac(R) in Chilean adults promotes robust cellular and humoral immune responses. The 0-28 schedule induced a stronger humoral immune response than the 0-14 schedule. FundingMinistry of Health, Government of Chile, Confederation of Production and Commerce & Millennium Institute on Immunology and Immunotherapy, Chile. Clinical trial numberNCT04651790. summaryTwo immunization schedules were evaluated for the inactivated SARS-CoV-2 vaccine, Coronavac(R), with two doses of the vaccine separated by two or four weeks. We compared humoral and cellular immune responses, showing they are mostly similar, with differences in neutralization capacities.
Subject(s)
COVID-19ABSTRACT
Background: Several vaccines have been developed to control the COVID-19 pandemic. CoronaVac (Sinovac Life Sciences), an inactivated SARS-CoV-2 vaccine, has demonstrated safety and immunogenicity in previous studies, preventing severe COVID-19 cases. We further investigated the safety and efficacy of two immunization schedules of CoronaVac in a non-inferiority trial in healthy adults. Methods: This is a multi-center and randomized clinical trial. Healthy adults were enrolled at eight centers in Chile. Participants were randomly assigned to two vaccination schedules, receiving two doses with either 14 (0-14) or 28 (0-28) days between each. 2302 participants were vaccinated. The primary safety and efficacy endpoints were solicited adverse events (AE) within 7 days after each dose and compared the number of cases of SARS-CoV-2 infection 14 days after the second dose between schedules, respectively. Findings: The most frequent local AE was pain at the injection site, which was less frequent in participants aged over 60 years. Other local AEs were reported in less than 5% of participants. The most frequent systemic AEs were headache, fatigue, and myalgia. The remaining AEs were minor allergic reactions and fever. Most AEs were mild and transient. There were no significant differences for local and systemic AE between schedules. No anaphylactic reactions or vaccine-related severe AEs were observed. 58 COVID-19 cases were confirmed, and all but two of them were mild. No differences were observed in protection between schedules. Interpretation: CoronaVac is safe, especially in over 60 years-old participants. Both schedules protected against COVID-19 hospitalizations. Funding: MINSAL, Chile, CPC & IMII, Chile.
Subject(s)
Pain , Headache , Mastocytosis, Systemic , Fever , Drug Hypersensitivity , Myalgia , COVID-19 , Epilepsies, Partial , FatigueABSTRACT
Background: The ongoing COVID-19 pandemic has had a significant impact worldwide, with an incommensurable social and economic burden. The rapid development of safe and protective vaccines against this disease is a global priority. CoronaVac is a vaccine prototype based on inactivated SARS-CoV-2, which has shown promising safety and immunogenicity profiles in pre-clinical studies and phase 1/2 trials in China. To this day, four phase 3 clinical trials are ongoing with CoronaVac in Brazil, Indonesia, Turkey, and Chile. This article reports the safety and immunogenicity results obtained in a subgroup of participants aged 18 years and older enrolled in the phase 3 Clinical Trial held in Chile. Methods: This is a multicenter phase 3 clinical trial. Healthcare workers aged 18 years and older were randomly assigned to receive two doses of CoronaVac or placebo separated by two weeks (0-14). We report preliminary safety results obtained for a subset of 434 participants, and antibody and cell-mediated immunity results obtained in a subset of participants assigned to the immunogenicity arm. The primary and secondary aims of the study include the evaluation of safety parameters and immunogenicity against SARS-CoV-2 after immunization, respectively. This trial is registered at clinicaltrials.gov (NCT04651790). Findings: The recruitment of participants occurred between November 27th, 2020, until January 9th, 2021. 434 participants were enrolled, 397 were 18-59 years old, and 37 were over 60 years old. Of these, 270 were immunized with CoronaVac, and the remaining 164 participants were inoculated with the corresponding placebo. The primary adverse reaction was pain at the injection site, with a higher incidence in the vaccine arm (55.6%) than in the placebo arm (40.0%). Moreover, the incidence of pain at the injection site in the 18-59 years old group was 58.4% as compared to 32.0% in the over 60 years old group. The seroconversion rate for specific anti-S1-RBD IgG was 47.8% for the 18-59 years old group 14 days post immunization (p.i.) and 95.6% 28 and 42 days p.i. For the over 60 years old group, the seroconversion rate was 18.1%, 100%, and 87.5% at 14, 28, and 42 days p.i., respectively. Importantly, we observed a 95.7% seroconversion rate in neutralizing antibodies for the 18-59 years old group 28 and 42 days p.i. The over 60 years old group exhibited seroconversion rates of 90.0% and 100% at 28 and 42 days p.i. Interestingly, we did not observe a significant seroconversion rate of anti-N-SARS-CoV-2 IgG for the 18-59 years old group. For the participants over 60 years old, a modest rate of seroconversion at 42 days p.i. was observed (37.5%). We observed a significant induction of a T cell response characterized by the secretion of IFN-gamma; upon stimulation with Mega Pools of peptides derived from SARS-CoV-2 proteins. No significant differences between the two age groups were observed for cell-mediated immunity. Interpretation: Immunization with CoronaVac in a 0-14 schedule in adults of 18 years and older in the Chilean population is safe and induces specific IgG production against the S1-RBD with neutralizing capacity, as well as the activation of T cells secreting IFN-gamma upon recognition of SARS-CoV-2 antigens. Funding: Ministry of Health of the Chilean Government; Confederation of Production and Commerce, Chile; Consortium of Universities for Vaccines and Therapies against COVID-19, Chile; Millennium Institute on Immunology and Immunotherapy.