Safety and Non-Inferiority Evaluation of Two Immunization Schedules with an Inactivated SARS-CoV-2 Vaccine in Adults: A Randomized Clinical Trial.

Several vaccines have been developed to control the COVID-19 pandemic. CoronaVac®, an inactivated SARS-CoV-2 vaccine, has demonstrated safety and immunogenicity, preventing severe COVID-19 cases. We investigate the safety and non-inferiority of two immunization schedules of CoronaVac® in a non-inferiority trial in healthy adults. A total of 2302 healthy adults were enrolled at 8 centers in Chile and randomly assigned to two vaccination schedules, receiving two doses with either 14 or 28 days between each. The primary safety and efficacy endpoints were solicited adverse events (AEs) within 7 days of each dose, and comparing the number of cases of SARS-CoV-2 infection 14 days after the second dose between the schedules, respectively. The most frequent local AE was pain at the injection site, which was less frequent in participants aged ≥60 years. Other local AEs were reported in less than 5% of participants. The most frequent systemic AEs were headache, fatigue, and myalgia. Most AEs were mild and transient. There were no significant differences for local and systemic AEs between schedules. A total of 58 COVID-19 cases were confirmed, and all but 2 of them were mild. No differences were observed in the proportion of COVID-19 cases between schedules. CoronaVac® is safe, especially in ≥60-year-old participants. Both schedules protected against COVID-19 hospitalization.

Safety and Immunogenicity of an Inactivated Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine in a Subgroup of Healthy Adults in Chile.

BACKGROUND: The development of effective vaccines against coronavirus disease 2019 is a global priority. CoronaVac is an inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine with promising safety and immunogenicity profiles. This article reports safety and immunogenicity results obtained for healthy Chilean adults aged ≥18 years in a phase 3 clinical trial. METHODS: Volunteers randomly received 2 doses of CoronaVac or placebo, separated by 2 weeks. A total of 434 volunteers were enrolled, 397 aged 18-59 years and 37 aged ≥60 years. Solicited and unsolicited adverse reactions were registered from all volunteers. Blood samples were obtained from a subset of volunteers and analyzed for humoral and cellular measures of immunogenicity. RESULTS: The primary adverse reaction in the 434 volunteers was pain at the injection site, with a higher incidence in the vaccine than in the placebo arm. Adverse reactions observed were mostly mild and local. No severe adverse events were reported. The humoral evaluation was performed on 81 volunteers. Seroconversion rates for specific anti-S1-receptor binding domain (RBD) immunoglobulin G (IgG) were 82.22% and 84.44% in the 18-59 year age group and 62.69% and 70.37% in the ≥60 year age group, 2 and 4 weeks after the second dose, respectively. A significant increase in circulating neutralizing antibodies was detected 2 and 4 weeks after the second dose. The cellular evaluation was performed on 47 volunteers. We detected a significant induction of T-cell responses characterized by the secretion of interferon-γ (IFN-γ) upon stimulation with Mega Pools of peptides from SARS-CoV-2. CONCLUSIONS: Immunization with CoronaVac in a 0-14 schedule in Chilean adults aged ≥18 years is safe, induces anti-S1-RBD IgG with neutralizing capacity, activates T cells, and promotes the secretion of IFN-γ upon stimulation with SARS-CoV-2 antigens.

Interim report: Safety and immunogenicity of an inactivated vaccine against SARS-CoV-2 in healthy chilean adults in a phase 3 clinical trial.

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 27 th , 2020, until January 9 th , 2021. 434 participants were enrolled, 397 were 18-59 years old, and 37 were ≥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 ≥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 ≥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 ≥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 ≥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-γ 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-γ, 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.

Respuesta virológica e inmunológica a la terapia anti-retroviral en pacientes portadores de infección por VIH atendidos en una red de salud académica de Chile / Virological and immunological outcomes to antiretroviral therapy in HIV-infected patients of an academic medical center in Chile

Introduction: Red Salud UC is an Academic health network where HIV-infected patients from the public and private health system are followed by a multidisplinary team. Aim: To determine virologic and immunologic response after 144 weeks of starting first antiretroviral therapy in these patients. Methods: A retrospective analysis of adult HIV patients attended between 1992 and 2011 was performed. Demographic and clinical characteristics, antiretroviral therapies data and immunologic and virologic outcomes were collected. CD4 count and HIV viral load changes up to 144 weeks after initiation of antiretroviral therapy were analyzed. Results: 860 patients were included in the analyses. Median age was 42 years, 93% were men. Median CD4+ count at baseline was 202 cells/mm³. The most used ART regimen was zidovudine/lamivudine plus efavirenz. First line anti-retroviral therapy was changed in 42% patients, being the most common cause, drug toxicity. At week 144, median CD4+ lymphocyte cell count was 449 cells/mm³. Ninety percent and 96% had undetectable viral load measured as < 50 copies/mL or < 400 copies/mL respectively. Discussion: First report of a university cohort, with CD4 and viral load follow up for 144 weeks, including Chilean patients from public and private system. After initiation of ART, an excellent immunologic and virologic response was observed in this cohort.

Introducción: La Red de Salud UC es una red académica de atención, donde pacientes portadores del VIH del área pública y privada de salud son atendidos por un equipo profesional multidisciplinario. Objetivo: Determinar las respuestas virológicas e inmunológicas a 144 semanas de iniciada la primera terapia antiretroviral en dichos pacientes. Métodos: Análisis retrospectivo de registros de pacientes adultos portadores de VIH atendidos entre 1992 y 2011. Se recolectaron datos demográficos, clínicos, terapia anti-retroviral, resultados inmunológicos y virológicos. Se analizaron los resultados de linfocitos T CD4+ y carga viral de VIH a las 144 semanas de iniciada la primera terapia anti-retroviral. Resultados: Fueron incluidos en el análisis 860 pacientes. El promedio de edad fue 42 años, 93% hombres. La mediana basal de LT CD4+ fue 202 céls/mm³. La terapia más utilizada fue zidovudina/lamivudina/efavirenz. En 42% de los pacientes se cambió la terapia de primera línea; la causa más común fue toxicidad a los anti-retrovirales. A la semana 144 de iniciada la terapia, la mediana de LT CD4+ fue de 449 céls/mm³. Alcanzaron cargas virales indetectables 90 y 96% con < 50 copias ARN/mL o < 400 copias ARN/mL respectivamente. Discusión: Primer reporte de pacientes tratados en un centro universitario, con seguimiento inmuno-virológico a 144 semanas, que incluye pacientes del área pública y privada de salud chilena. Después del inicio de la terapia, se observó una excelente respuesta inmuno-virológica.

Virological and immunological outcomes to antiretroviral therapy in HIV-infected patients of an academic medical center in Chile.

INTRODUCTION: Red Salud UC is an Academic health network where HIV-infected patients from the public and private health system are followed by a multidisplinary team. AIM: To determine virologic and immunologic response after 144 weeks of starting first antiretroviral therapy in these patients. METHODS: A retrospective analysis of adult HIV patients attended between 1992 and 2011 was performed. Demographic and clinical characteristics, antiretroviral therapies data and immunologic and virologic outcomes were collected. CD4 count and HIV viral load changes up to 144 weeks after initiation of antiretroviral therapy were analyzed. RESULTS: 860 patients were included in the analyses. Median age was 42 years, 93% were men. Median CD4+ count at baseline was 202 cells/mm³. The most used ART regimen was zidovudine/lamivudine plus efavirenz. First line anti-retroviral therapy was changed in 42% patients, being the most common cause, drug toxicity. At week 144, median CD4+ lymphocyte cell count was 449 cells/mm³. Ninety percent and 96% had undetectable viral load measured as < 50 copies/mL or < 400 copies/mL respectively. DISCUSSION: First report of a university cohort, with CD4 and viral load follow up for 144 weeks, including Chilean patients from public and private system. After initiation of ART, an excellent immunologic and virologic response was observed in this cohort.