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Outcomes of hematopoietic stem cell gene therapy for Wiskott-Aldrich syndrome
(2023)
Roxane Labrosse
;
Julia I. Chu
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Myriam A. Armant
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John K. Everett
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Danilo Pellin
<jats:title>Abstract</jats:title> <jats:p>Wiskott-Aldrich syndrome (WAS) is a rare X-linked disorder characterized by combined immunodeficiency, eczema, microthrombocytopenia, autoimmunity, and lymphoid malignancies. Gene therapy (GT) to modify autologous CD34+ cells is an emerging alternative treatment with advantages over standard allogeneic hematopoietic stem cell transplantation for patients who lack well-matched donors, avoiding graft-versus-host-disease. We report the outcomes of a phase 1/2 clinical trial in which 5 patients with severe WAS underwent GT using a self-inactivating lentiviral vector expressing the human WAS complementary DNA under the control of a 1.6-kB fragment of the autologous promoter after busulfan and fludarabine conditioning. All patients were alive and well with sustained multilineage vector gene marking (median follow-up: 7.6 years). Clinical improvement of eczema, infections, and bleeding diathesis was universal. Immune function was consistently improved despite subphysiologic levels of transgenic WAS protein expression. Improvements in platelet count and cytoskeletal function in myeloid cells were most prominent in patients with high vector copy number in the transduced product. Two patients with a history of autoimmunity had flares of autoimmunity after GT, despite similar percentages of WAS protein–expressing cells and gene marking to those without autoimmunity. Patients with flares of autoimmunity demonstrated poor numerical recovery of T cells and regulatory T cells (Tregs), interleukin-10–producing regulatory B cells (Bregs), and transitional B cells. Thus, recovery of the Breg compartment, along with Tregs appears to be protective against development of autoimmunity after GT. These results indicate that clinical and laboratory manifestations of WAS are improved with GT with an acceptable safety profile. This trial is registered at clinicaltrials.gov as #NCT01410825.</jats:p>
12Scopus© Citations 30
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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
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Pablo Díaz
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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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Different Safety Pattern of an Inactivated SARS-CoV-2 Vaccine (CoronaVac®) According to Age Group in a Pediatric Population from 3 to 17 Years Old, in an Open-Label Study in Chile
(2023)
Nicole Le Corre
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Katia Abarca
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Patricio Astudillo
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Marcela Potin
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Sofía López
<jats:p>During the COVID-19 pandemic, the importance of vaccinating children against SARS-CoV-2 was rapidly established. This study describes the safety of CoronaVac® in children and adolescents between 3- and 17-years-old in a multicenter study in Chile with two vaccine doses in a 4-week interval. For all participants, immediate adverse events (AEs), serious AEs (SAEs), and AEs of special interest (AESIs) were registered throughout the study. In the safety subgroup, AEs were recorded 28 days after each dose. COVID-19 surveillance was performed throughout the study. A total of 1139 individuals received the first and 1102 the second dose of CoronaVac®; 835 were in the safety subgroup. The first dose showed the highest number of AEs: up to 22.2% of participants reported any local and 17.1% systemic AE. AEs were more frequent in adolescents after the first dose, were transient, and mainly mild. Pain at the inoculation site was the most frequent AE for all ages. Fever was the most frequent systemic AE for 3–5 years old and headache in 6–17 years old. No SAEs or AESIs related to vaccination occurred. Most of the COVID-19 cases were mild and managed as outpatients. CoronaVac® was safe and well tolerated in children and adolescents, with different safety patterns according to age.</jats:p>
Scopus© Citations 3 3
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Seroprevalence of Natural and Acquired Immunity against the SARS-CoV-2 Virus in a Population Cohort from Two Chilean Cities, 2020–2022
(2023)
Loreto Núñez-Franz
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Muriel Ramírez-Santana
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RUBILAR RAMIREZ, PAOLA
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Macarena Said
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VIAL COX, MARIA CECILIA
<jats:p>Background: Chile has achieved the highest coverage for vaccines against the SARS-CoV-2 virus worldwide. Objective: To assess the progression of immunity (natural and acquired by vaccine) in a cohort from two Chilean cities. Methods: Individuals (n = 386) who participated in three phases of population-based serial prevalence studies were included (2020–2021 and 2022). Presence of SARS-CoV-2 antibodies was measured in serum. Data including time of vaccination and type of vaccine received were analysed with descriptive statistics. Results: Seroprevalence was 3.6% in the first round and increased to 96.9% in the second and 98.7% in the third. In the third round, 75% of individuals who had received the basal full scheme were seropositive at 180 days or more since their last dose; 98% of individuals who received one booster dose were seropositive at 180 days or more, and 100% participants who received two boosters were seropositive, regardless of time since their last dose. Participants receiving mRNA vaccines had higher seroprevalence rates over time. Conclusions: The high vaccination coverage in Chile enabled the population to maintain high levels of antibodies. Vaccination boosters are essential to maintain immunity over time, which also depends on the type of vaccine administered.</jats:p>
1Scopus© Citations 12
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Neutralizing antibodies induced by homologous and heterologous boosters in CoronaVac vaccines in Chile
(2023)
ACEVEDO ROMO, JOHANNA PATRICIA
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Mónica L. Acevedo
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Aracelly Gaete-Argel
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ARAOS BRALIC, RAFAEL IGNACIO
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Cecilia Gonzalez
Scopus© Citations 4 21
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Mucosal Vaccination with Lactococcus lactis-Secreting Surface Immunological Protein Induces Humoral and Cellular Immune Protection against Group B Streptococcus in a Murine Model
(2020)
Diego A. Diaz-Dinamarca
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Carlos Hernandez
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Daniel F. Escobar
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Daniel A. Soto
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Guillermo A. Muñoz
<jats:p>Group B Streptococcus (GBS) is the primary etiological agent of sepsis and meningitis in newborns and is associated with premature birth and stillbirth. The development of a licensed vaccine is one of the pending challenges for the World Health Organization. Previously, we showed that oral immunization with surface immune protein (SIP) decreases vaginal colonization of GBS and generates functional opsonizing antibodies, which was determined by opsonophagocytic assays (OPA) in vitro. We also showed that the protein has an adjuvant vaccine profile. Therefore, an oral vaccine based on SIP may be an attractive alternative to employ in the development of new vaccines against GBS. Lactococcus lactis is a highlighted oral vaccine probiotic inducer of the mucosal immune response. This bacterium could serve as an antigen-delivering vehicle for the development of an edible vaccine and has been used in clinical trials. In this study, we showed that an oral vaccine with a recombinant L. lactis strain secreting SIP from GBS (rL. lactis-SIP) can induce protective humoral and cellular immunity in an experimental model of GBS vaginal colonization in C57BL/6 mice. Mice immunized with rL. lactis-SIP were protected against clinical symptoms and bacterial colonization after GBS vaginal colonization. Our rL. lactis-SIP vaccine also induces an increase of immunoglobulin G (IgG) and immunoglobulin A (IgA) specifically against SIP. The adoptive transfer of serum from vaccinated mice to naïve mice generated protection against GBS vaginal colonization. Moreover, the rL. lactis-SIP strain induces the activation of SIP-specific T cells, which could decrease GBS vaginal colonization and generate protective antibodies when transferred to other mice. Our experimental observations strongly support the notion that rL. lactis-SIP induces protective humoral and cellular immunity and could be considered as a novel alternative in the development of vaccines for GBS.</jats:p>
9Scopus© Citations 25
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Immunity certification for COVID-19: ethical considerations
(2020)
Teck Chuan Voo
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Andreas A Reis
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Beatriz Thomé
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Calvin WL Ho
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Clarence C Tam
6Scopus© Citations 39
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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
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Katia Abarca
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GONZALEZ, PABLO
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Nicolás M S Gálvez
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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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Deep immunophenotyping reveals biomarkers of multisystemic inflammatory syndrome in children in a Latin American cohort
(2022)
REY JURADO, EMMA
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Yazmin Espinosa
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Camila Astudillo
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CORTES SALINAS, LINA JIMENA
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HORMAZABAL CASTILLO, JUAN PATRICIO
Scopus© Citations 16 8
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Inactivated Vaccine-Induced SARS-CoV-2 Variant-Specific Immunity in Children
(2022)
Jorge A. Soto
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Felipe Melo-González
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Cristián Gutierrez-Vera
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Bárbara M. Schultz
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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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