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    Humoral immunity against SARS-CoV-2 evoked by heterologous vaccination groups using the CoronaVac (Sinovac) and BNT162b2 (Pfizer/BioNTech) vaccines in Chile
    (2023)
    Diego A. Díaz-Dinamarca
    ;
    Pablo Díaz
    ;
    Gisselle Barra
    ;
    Rodrigo Puentes
    ;
    Loredana Arata
    <jats:sec><jats:title>Introduction</jats:title><jats:p>Severe acute respiratory syndrome virus 2 (SARS-CoV-2) has caused over million deaths worldwide, with more than 61,000 deaths in Chile. The Chilean government has implemented a vaccination program against SARS-CoV-2, with over 17.7 million people receiving a complete vaccination scheme. The final target is 18 million individuals. The most common vaccines used in Chile are CoronaVac (Sinovac) and BNT162b2 (Pfizer-Biotech). Given the global need for vaccine boosters to combat the impact of emerging virus variants, studying the immune response to SARS-CoV-2 is crucial. In this study, we characterize the humoral immune response in inoculated volunteers from Chile who received vaccination schemes consisting of two doses of CoronaVac [CoronaVac (2x)], two doses of CoronaVac plus one dose of BNT162b2 [CoronaVac (2x) + BNT162b2 (1x)], and three doses of BNT162b2 [BNT162b2 (3x)].</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We recruited 469 participants from Clínica Dávila in Santiago and the Health Center Víctor Manuel Fernández in the city of Concepción, Chile. Additionally, we included participants who had recovered from COVID-19 but were not vaccinated (RCN). We analyzed antibodies, including anti-N, anti-S1-RBD, and neutralizing antibodies against SARS-CoV-2.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>We found that antibodies against the SARS-CoV-2 nucleoprotein were significantly higher in the CoronaVac (2x) and RCN groups compared to the CoronaVac (2x) + BNT162b2 (1x) or BNT162b2 (3x) groups. However, the CoronaVac (2x) + BNT162b2 (1x) and BNT162b2 (3x) groups exhibited a higher concentration of S1-RBD antibodies than the CoronaVac (2x) group and RCN group. There were no significant differences in S1-RBD antibody titers between the CoronaVac (2x) + BNT162b2 (1x) and BNT162b2 (3x) groups. Finally, the group immunized with BNT162b2 (3x) had higher levels of neutralizing antibodies compared to the RCN group, as well as the CoronaVac (2x) and CoronaVac (2x) + BNT162b2 (1x) groups.</jats:p></jats:sec><jats:sec><jats:title>Discussion</jats:title><jats:p>These findings suggest that vaccination induces the secretion of antibodies against SARS-CoV-2, and a booster dose of BNT162b2 is necessary to generate a protective immune response. In the current state of the pandemic, these data support the Ministry of Health of the Government of Chile’s decision to promote heterologous vaccination as they indicate that a significant portion of the Chilean population has neutralizing antibodies against SARS-CoV-2.</jats:p></jats:sec>
      7Scopus© Citations 7
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    Mutation in a SARS-CoV-2 Haplotype from Sub-Antarctic Chile Reveals New Insights into the Spike’s Dynamics
    (2021)
    Jorge González-Puelma
    ;
    Jacqueline Aldridge
    ;
    Marco Montes de Oca
    ;
    Mónica Pinto
    ;
    Roberto Uribe-Paredes
    <jats:p>The emergence of SARS-CoV-2 variants, as observed with the D614G spike protein mutant and, more recently, with B.1.1.7 (501Y.V1), B.1.351 (501Y.V2) and B.1.1.28.1 (P.1) lineages, represent a continuous threat and might lead to strains of higher infectivity and/or virulence. We report on the occurrence of a SARS-CoV-2 haplotype with nine mutations including D614G/T307I double-mutation of the spike. This variant expanded and completely replaced previous lineages within a short period in the subantarctic Magallanes Region, southern Chile. The rapid lineage shift was accompanied by a significant increase of cases, resulting in one of the highest incidence rates worldwide. Comparative coarse-grained molecular dynamic simulations indicated that T307I and D614G belong to a previously unrecognized dynamic domain, interfering with the mobility of the receptor binding domain of the spike. The T307I mutation showed a synergistic effect with the D614G. Continuous surveillance of new mutations and molecular analyses of such variations are important tools to understand the molecular mechanisms defining infectivity and virulence of current and future SARS-CoV-2 strains.</jats:p>
      1Scopus© Citations 9
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    Scopus© Citations 4  21
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    Safety and Immunogenicity of an Inactivated Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine in a Subgroup of Healthy Adults in Chile
    (2021)
    Susan M Bueno
    ;
    Katia Abarca
    ;
    GONZALEZ, PABLO
    ;
    Nicolás M S Gálvez
    ;
    Jorge A Soto
    <jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>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.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>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.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>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.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>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.</jats:p> </jats:sec>
    Scopus© Citations 75  1
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    Scopus© Citations 16  8
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    Inactivated Vaccine-Induced SARS-CoV-2 Variant-Specific Immunity in Children
    (2022)
    Jorge A. Soto
    ;
    Felipe Melo-González
    ;
    Cristián Gutierrez-Vera
    ;
    Bárbara M. Schultz
    ;
    Roslye V. Berríos-Rojas
    <jats:p>This work evaluated the immune response induced by two doses of CoronaVac separated by 4 weeks in healthy children and adolescents in Chile. To date, few studies have described the effects of CoronaVac in the pediatric population.</jats:p>
      1Scopus© Citations 20  16
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    Evaluation of the Immune Response Induced by CoronaVac 28-Day Schedule Vaccination in a Healthy Population Group
    (2022)
    Alejandro Escobar
    ;
    Felipe E. Reyes-López
    ;
    Mónica L. Acevedo
    ;
    Luis Alonso-Palomares
    ;
    Fernando Valiente-Echeverría
    <jats:p>CoronaVac vaccine from Sinovac Life Science is currently being used in several countries. In Chile, the effectiveness of preventing hospitalization is higher than 80% with a vaccination schedule. However, to date, there are no data about immune response induction or specific memory. For this reason, we recruited 15 volunteers without previous suspected/diagnosed COVID-19 and with negative PCR over time to evaluate the immune response to CoronaVac 28 and 90 days after the second immunization (dpi). The CoronaVac administration induces total and neutralizing anti-spike antibodies in all vaccinated volunteers at 28 and 90 dpi. Furthermore, using ELISpot analysis to assay cellular immune responses against SARS-CoV-2 spike protein, we found an increase in IFN-gamma- and Granzyme B-producing cells in vaccinated volunteers at 28 and 90 dpi. Together, our results indicate that CoronaVac induces a robust humoral immune response and cellular immune memory of at least 90 dpi.</jats:p>
      23Scopus© Citations 19
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      4Scopus© Citations 9