RESUMEN

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are pivotal in combating coronavirus disease 2019 (COVID-19); however, the declining antibody titers postvaccination pose challenges for sustained protection and herd immunity. Although gut microbiome is reported to affect the early antibody response after vaccination, its impact on the longevity of vaccine-induced antibodies remains unexplored. METHODS: A prospective cohort study was conducted involving 44 healthy adults who received two doses of either the BNT162b2 or ChAdOx1 vaccine, followed by a BNT162b2 booster at six months. The gut microbiome was serially analyzed using 16S rRNA and shotgun sequencing, while humoral immune response was assessed using a SARS-CoV-2 spike protein immunoassay. RESULTS: Faecalibacterium prausnitzii was associated with robust and persistent antibody responses post-BNT162b2 vaccination. In comparison, Escherichia coli was associated with a slower antibody decay following ChAdOx1 vaccination. The booster immune response was correlated with metabolic pathways involving cellular functions and aromatic amino acid synthesis. CONCLUSIONS: The findings of this study underscored the potential interaction between the gut microbiome and the longevity/boosting effect of antibodies following vaccination against SARS-CoV-2. The identification of specific microbial associations suggests the prospect of microbiome-based strategies for enhancing vaccine efficacy.

Asunto(s)

Anticuerpos Antivirales , Vacuna BNT162 , COVID-19 , Microbioma Gastrointestinal , Inmunización Secundaria , SARS-CoV-2 , Vacunación , Humanos , Microbioma Gastrointestinal/inmunología , Masculino , Femenino , Adulto , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , SARS-CoV-2/inmunología , COVID-19/inmunología , COVID-19/prevención & control , Vacuna BNT162/inmunología , Vacunas contra la COVID-19/inmunología , Persona de Mediana Edad , ChAdOx1 nCoV-19/inmunología , Estudios Prospectivos , Formación de Anticuerpos/inmunología , Glicoproteína de la Espiga del Coronavirus/inmunología , Inmunidad Humoral/inmunología , Adulto Joven

RESUMEN

The severe acute respiratory syndrome coronavirus 2 pandemic started in December 2019, spread like wildfire and took an immense toll on human life. ChAdOx1 nCoV-19 vaccine was used worldwide for the prevention of Covid-19. Covid-19 has been implicated in the causation of severe haemophagocytic lymphohistiocytosis (HLH) syndrome. However, the same has not been reported with ChAdOx1 nCoV-19 vaccine in the literature. We report a young man who developed secondary HLH post-ChAdOx1 nCoV-19 vaccination.

Asunto(s)

Vacunas contra la COVID-19 , COVID-19 , ChAdOx1 nCoV-19 , Linfohistiocitosis Hemofagocítica , Humanos , Linfohistiocitosis Hemofagocítica/etiología , Linfohistiocitosis Hemofagocítica/diagnóstico , Masculino , ChAdOx1 nCoV-19/efectos adversos , COVID-19/prevención & control , COVID-19/complicaciones , Vacunas contra la COVID-19/efectos adversos , Adulto , SARS-CoV-2/inmunología

RESUMEN

Herpes zoster is a viral infection caused due to the reactivation of varicella-zoster virus that is localized to a single dermatome unilaterally. The factors responsible for its reactivation are increasing age, immunosuppressive drugs, malignancies, chronic liver and renal diseases. Herpes zoster was found to be one of the cutaneous manifestations of coronavirus disease 2019 (Covid-19). Various skin manifestations post-vaccination are being reported, which include injection site urticarial, maculopapular rash and positive dermographism. We report a patient of herpes zoster triggered by the viral vector (ChAdOx1 nCoV-19) coronavirus vaccine (recombinant).

Asunto(s)

Vacunas contra la COVID-19 , COVID-19 , ChAdOx1 nCoV-19 , Herpes Zóster , Humanos , Herpes Zóster/prevención & control , Herpes Zóster/inmunología , Vacunas contra la COVID-19/efectos adversos , Vacunas contra la COVID-19/administración & dosificación , COVID-19/prevención & control , COVID-19/inmunología , Masculino , SARS-CoV-2/inmunología , Persona de Mediana Edad , Femenino

RESUMEN

Due to the persisting development of SARS-CoV-2 variants, studies on the kinetics, duration, and function of antibodies are essential for vaccine development and long-term immunity prediction. This longitudinal study examined post-vaccination antibody responses in people after receiving CoronaVac or ChAdOx1 vaccines with or without a history of SARS-CoV-2 infection. Conducted in Indonesia between August 2021 and May 2023, this study involved 121 participants divided into two groups based on the received vaccine types and monitored for 18 months post-second dose vaccination by assessing the binding antibody (BAb) level and neutralizing antibody (NAb) inhibition rate at six time points. The study also documented the participants' age, gender, and body mass index (BMI). Before the first dose vaccination, 85 (70.2%) participants were reactive BAb (defined by BAb level ≥50 AU/mL) indicating a history of infection. In the CoronaVac group, only 53.1% were reactive BAb. However, 100% of participants were positive NAb (defined by NAb inhibition rate ≥30%), which indicates a past history of infection with low initial or rapidly decreasing BAb levels. In the ChAdOx1 group, 81.9% of participants were reactive, while only 54.2% were positive NAb, suggesting a recent infection with a high BAb level but a relatively low NAb inhibition rate. During the 18 months post-second dose vaccination, the BAb levels fluctuated. However, 100% of participants were positive NAb. No significant difference in antibody response was documented among participants with or without infection history. Also, no significant impact was presented by the factors of sex, age, and BMI. The findings highlight the crucial of the vaccine in public health and how vaccination strategies could be optimized effectively during and after the post-pandemic.

Asunto(s)

Anticuerpos Neutralizantes , Anticuerpos Antivirales , Vacunas contra la COVID-19 , COVID-19 , SARS-CoV-2 , Humanos , Indonesia/epidemiología , Masculino , Estudios Longitudinales , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/inmunología , Femenino , COVID-19/prevención & control , COVID-19/inmunología , COVID-19/epidemiología , Adulto , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Persona de Mediana Edad , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/sangre , SARS-CoV-2/inmunología , ChAdOx1 nCoV-19 , Adulto Joven , Vacunación

RESUMEN

To achieve global herd immunity, widespread vaccination is the most effective strategy. Vaccines stimulate the immune system, generating cytokines and chemokines, isotype antibodies, and neutralizing antibodies; all these molecules collectively provide a more comprehensive characterization of the immune response post-vaccination. We conducted a longitudinal study in northwestern Mexico, involving 120 individuals before vaccination and after the first dose of the SARS-CoV-2 vaccine, and 46 individuals after their second dose. Our findings reveal that antibody levels stabilize over time; cytokine levels generally increase following the first dose but decrease after the second dose and higher than normal levels in IgG1 and IgG3 concentrations are present. Most of the innate cytokines determined in this study were higher after the first dose of the vaccine. Regardless of previous infection history, this finding suggests that the first dose of the vaccine is crucial and may stimulate immunity by enhancing the innate immune response. Conversely, increased levels of IL-4, indicative of a Th2 response, were found in individuals without prior exposure to the virus and in those vaccinated with CoronaVac. These results suggest that the immune response to COVID-19 vaccines is multi-faceted, with preexisting immunity potentiating a more robust innate response. Vaccine type plays a critical role, with genetic vaccines favoring a Th1 response and inactivated vaccines like CoronaVac skewing toward a Th2 profile.

Asunto(s)

Anticuerpos Neutralizantes , Anticuerpos Antivirales , Vacuna BNT162 , Vacunas contra la COVID-19 , COVID-19 , ChAdOx1 nCoV-19 , Citocinas , SARS-CoV-2 , Humanos , COVID-19/inmunología , COVID-19/prevención & control , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Masculino , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Citocinas/inmunología , Femenino , Adulto , Persona de Mediana Edad , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/inmunología , Vacuna BNT162/inmunología , Vacuna BNT162/administración & dosificación , México , Estudios Longitudinales , ChAdOx1 nCoV-19/inmunología , ChAdOx1 nCoV-19/administración & dosificación , SARS-CoV-2/inmunología , Células Th2/inmunología , Células TH1/inmunología , Inmunoglobulina G/sangre , Vacunación , Vacunas de Productos Inactivados/inmunología , Vacunas de Productos Inactivados/administración & dosificación , Adulto Joven , Anciano

Asunto(s)

Infecciones por Virus Sincitial Respiratorio , Vacunas contra Virus Sincitial Respiratorio , Humanos , ChAdOx1 nCoV-19 , Infecciones por Virus Sincitial Respiratorio/prevención & control , Vacunas contra Virus Sincitial Respiratorio/efectos adversos , Vacunas contra Virus Sincitial Respiratorio/inmunología , Vacunas Virales

RESUMEN

BACKGROUND: Patients with immune-mediated rheumatic diseases (IMRDs) have been prioritized for COVID-19 vaccination to mitigate the infection severity risks. Patients with rheumatoid arthritis (RA) are at a high risk of severe COVID-19 outcomes, especially those under immunosuppression or with associated comorbidities. However, few studies have assessed the safety of the COVID-19 vaccine in patients with RA. OBJECTIVE: To evaluate the safety of vaccines against SARS-CoV-2 in patients with RA. METHODS: This data are from the study "Safety and Efficacy on COVID-19 Vaccine in Rheumatic Diseases," a Brazilian multicentric prospective phase IV study to evaluate COVID-19 vaccine in IMRDs in Brazil. Adverse events (AEs) in patients with RA of all centers were assessed after two doses of ChAdOx1 (Oxford/AstraZeneca) or CoronaVac (Sinovac/Butantan). Stratification of postvaccination AEs was performed using a diary, filled out daily and returned at the end of 28 days for each dose. RESULTS: A total of 188 patients with RA were include, 90% female. CoronaVac was used in 109 patients and ChAdOx1 in 79. Only mild AEs were observed, mainly after the first dose. The most common AEs after the first dose were pain at the injection (46,7%), headache (39,4%), arthralgia (39,4%), myalgia (30,5%) and fatigue (26,6%), and ChAdOx1 had a higher frequency of pain at the injection (66% vs 32 %, p < 0.001) arthralgia (62% vs 22%, p < 0.001) and myalgia (45% vs 20%, p < 0.001) compared to CoronaVac. The more common AEs after the second dose were pain at the injection (37%), arthralgia (31%), myalgia (23%), headache (21%) and fatigue (18%). Arthralgia (41,4% vs 25%, p = 0.02) and pain at injection (51,4% vs 27%, p = 0.001) were more common with ChAdOx1. No serious AEs were related. With Regard to RA activity level, no significant difference was observed between the three time periods for both COVID-19 vaccines. CONCLUSION: In the comparison between the two immunizers in patients with RA, local reactions and musculoskeletal symptoms were more frequent with ChAdOx1 than with CoronaVac, especially after the first dose. In summary, the AE occurred mainly after the first dose, and were mild, like previous data from others immunizing agents in patients with rheumatoid arthritis. Vaccination did not worsen the degree of disease activity.

Asunto(s)

Artritis Reumatoide , Vacunas contra la COVID-19 , COVID-19 , ChAdOx1 nCoV-19 , Humanos , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/complicaciones , Femenino , Masculino , Brasil/epidemiología , Persona de Mediana Edad , COVID-19/prevención & control , COVID-19/complicaciones , Vacunas contra la COVID-19/efectos adversos , Vacunas contra la COVID-19/administración & dosificación , ChAdOx1 nCoV-19/efectos adversos , Estudios Prospectivos , Adulto , SARS-CoV-2/inmunología , Anciano , Cefalea/inducido químicamente , Cefalea/etiología , Mialgia/inducido químicamente , Mialgia/etiología , Artralgia/etiología , Vacunas de Productos Inactivados

RESUMEN

In April 2024, in a class action suit for compensation to families of persons suffering injury or death after vaccination with AstraZeneca's (AZ) Covid-19 vaccine [1], the manufacturer admitted in a UK court that the Oxford-AZ Covid-19 vaccine could cause a rare and potentially fatal blood clotting disorder ("thrombosis with thrombocytopenia syndrome" or TTS, which when triggered by a vaccine is called "vaccine induced thrombocytopenia and thrombosis, or VITT) [2]. The AZ Covid-19 vaccine is a chimpanzee adenovirus vectored vaccine encoding the SARS-CoV2 spike protein (ChAdOx1-S) marketed under the names Covishield and Vaxzevria.

Asunto(s)

Vacunas contra la COVID-19 , COVID-19 , ChAdOx1 nCoV-19 , Compensación y Reparación , SARS-CoV-2 , Vacunación , Humanos , COVID-19/prevención & control , Compensación y Reparación/ética , Compensación y Reparación/legislación & jurisprudencia , Vacunas contra la COVID-19/efectos adversos , Vacunación/ética , Vacunación/legislación & jurisprudencia , Vacunación/efectos adversos , Reino Unido , India , Trombocitopenia/inducido químicamente

RESUMEN

Maintenance hemodialysis (MHD) patients exhibit compromised immune responses, leading to lower immunogenicity to the COVID-19 vaccine than the general population. The metabolomic factors influencing COVID-19 vaccine response in MHD patients remain elusive. A cross-sectional study was conducted with 30 MHD patients, divided into three vaccine regimen groups (N= 10 per group): homologous CoronaVac® (SV-SV), homologous ChAdOx1 nCoV-19 (AZ-AZ), and heterologous prime-boost (SV-AZ). Plasma samples were collected at baseline and at 28 days after the final dose to analyze 92 metabolomic levels using targeted metabolomics. The study included 30 MHD patients (mean age 56.67 ± 10.79 years) with similar neutralizing antibody (nAb) levels across vaccine regimens. The most significant differences in metabolomics were found between AZ-AZ and SV-SV, followed by SV-AZ versus SV-SV, and AZ-AZ versus SV-AZ. Overall, the metabolomic changes involved amino acids like glutamate and phenylalanine, and phospholipids. Prevaccination metabolomic profiles, including PG (38:1), lysoPE (20:2), lysoPC (18:2), lysoPI (18:1), and PC (34:2), exhibited negative correlations with postvaccination nAb levels. Different COVID-19 vaccine regimens had unique interactions with the immune response in MHD patients. Amino acid and phospholipid metabolisms play crucial roles in nAb formation, with the phospholipid metabolism being a potentially predictive marker of vaccine immunogenicity among MHD patients.

Asunto(s)

Vacunas contra la COVID-19 , COVID-19 , Metaboloma , Diálisis Renal , Humanos , Persona de Mediana Edad , Masculino , Femenino , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , COVID-19/inmunología , COVID-19/sangre , COVID-19/prevención & control , Anciano , Estudios Transversales , Adulto , Inmunogenicidad Vacunal , SARS-CoV-2/inmunología , ChAdOx1 nCoV-19/inmunología , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/sangre

RESUMEN

The vaccination against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is an important public health strategy to prevent people from the pandemic. Vaccines are a game-changing tool, it is essential to understand the adverse events after COVID-19 vaccination. This study explored the adverse events of COVID-19 Vaccination Oxford-AstraZeneca, Pfizer-BioNTech, Moderna, Johnson and Johnson on Guillain-Barré Syndrome (GBS). In this study, initially 128 documents were identified from the databases, including Pub-Med, Web of Science-Clarivate Analytics, Scopus, and Google Scholar. The articles on COVID-19 vaccination and GBs were searched using the keywords "SARS-CoV-2, COVID-19, Vaccination, and Guillain Barré Syndrome, GBS", finally, 16 documents were included in the analysis and synthesis. After administering 1,680,042,214 doses of COVID-19 vaccines, 6177 cases were identified with 10.5 cases per million vaccine doses. A significant positive risk was found between COVID-19 vaccine administration and GBS with a risk rate of RR 1.97 (95% CI 1.26-3.08, p = 0.01). The mRNA vaccines were associated with 2076 cases, and 1,237,638,401 vaccine doses were linked with 4.47 GBS events per million vaccine doses. The first dose of the m-RNA vaccine was associated with 8.83 events per million doses compared to the second dose with 02 events per million doses. The viral-vector vaccine doses 193,535,249 were linked to 1630 GBS cases with 11.01 cases per million doses. The incidence of GBS after the first dose was 17.43 compared to 1.47 cases per million in the second dose of the viral-vector vaccine. The adverse events of the Oxford-AstraZeneca vaccine were linked to 1339 cases of GBS following 167,786,902 vaccine doses, with 14.2 cases per million doses. The Oxford-AstraZeneca vaccine significantly increased the risk of GBS RR: 2.96 (95% CI 2.51-3.48, p = 0.01). For the Pfizer-BioNTech vaccine, there were 7.20 cases per million doses of the vaccine, and no significant association was identified between the Pfizer-BioNTech vaccine and GBS incidence RR: 0.99 (95% CI 0.75-1.32, p = 0.96). Moderna vaccine was related with 419 cases of GBS after administering 420,420,909 doses, with 2.26 cases per million doses. However, Johnson and Johnson's vaccination was linked to 235 GBS after 60,256,913 doses of the vaccine with 8.80 cases per million doses. A significant association was seen between the risk of GBS and Ad.26.COV2. S vaccine, RR: 2.47 (95% CI 1.30-4.69, p < 0.01). Overall, a significant association was seen between the COVID-19 vaccines and the risk of GBS. The incidence of GBS was higher after the first dose compared to GBS cases per million in the second dose.

Asunto(s)

Vacunas contra la COVID-19 , COVID-19 , Síndrome de Guillain-Barré , Humanos , Vacuna BNT162/efectos adversos , ChAdOx1 nCoV-19/efectos adversos , COVID-19/prevención & control , COVID-19/epidemiología , Vacunas contra la COVID-19/efectos adversos , Síndrome de Guillain-Barré/inducido químicamente , Síndrome de Guillain-Barré/epidemiología , Vacunación/efectos adversos

RESUMEN

BACKGROUND: For pathogens which cause infections that present asymptomatically, evaluating vaccine efficacy (VE) against asymptomatic infection is important for understanding a vaccine's potential epidemiological impact. Regular testing for subclinical infections is a potentially valuable strategy but its success hinges on participant adherence and minimising false positives. This paper describes the implementation and adherence to weekly testing in a COVID-19 vaccine trial. METHODS: COV002 was a phase 2/3 trial assessing the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2. Asymptomatic infections were detected using weekly self-administered swabs for RT-PCR testing. We analysed adherence using mixed-effects regression models and estimated the probability of true and false positive asymptomatic infections using estimates of adherence and testing characteristics. FINDINGS: 356,551 tests were self-administered by 10,811 participants during the 13-month follow-up. Median adherence was 75.0% (IQR 42·6-90·9), which translated to a 74·5% (IQR 50·9-78·8) probability of detecting a positive asymptomatic infection during the swabbing period, and between 21 and 96 false positives during VE evaluation. The odds of returning a swab declined by 8% per week and further after testing positive and unblinding. Adherence was higher in older age groups, females and non-healthcare workers. INTERPRETATION: The COV002 trial demonstrated the feasibility of running a long-term regular asymptomatic testing strategy. This information could be valuable for designing future phase III vaccine trials in which infection is an outcome. FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, AstraZeneca.

Asunto(s)

Infecciones Asintomáticas , Vacunas contra la COVID-19 , COVID-19 , SARS-CoV-2 , Humanos , COVID-19/prevención & control , COVID-19/epidemiología , COVID-19/diagnóstico , Femenino , Masculino , Vacunas contra la COVID-19/administración & dosificación , Adulto , Persona de Mediana Edad , SARS-CoV-2/inmunología , ChAdOx1 nCoV-19 , Eficacia de las Vacunas/estadística & datos numéricos , Adulto Joven , Anciano , Cooperación del Paciente/estadística & datos numéricos

RESUMEN

OBJECTIVES: Impact of frailty towards immunogenicity and reactogenicity of BNT162b2 boosters administered via intramuscular or intradermal routes in a Thai geriatric population DESIGN: Prospective, randomized, open-labeled. SETTING: Siriraj Hospital, Thailand. PARTICIPANTS: Geriatric adults aged ≥65 years. INTERVENTION: 10 µg intradermal or 30 µg intramuscular BNT162b2 (Pfizer-BioNTech). MEASUREMENTS: Anti-SARS-CoV-2 receptor binding domain IgG, neutralizing antibodies (NAb), and interferon-gamma producing cells against Wuhan and Omicron BA.4/5. Analyses were stratified based on participants' Clinical Frailty Scale. RESULTS: A total of 139 participants were included in the analysis. Two-four weeks post-booster administration, NAb titers against Wuhan but not Omicron BA.4/5 were significantly lower among frail participants than non-frail participants who received intramuscular administration. Spike-specific T cell responses were similar for frail and non-frail participants, regardless of administration route. Frail participants who received intradermal BNT162b2 had fewer local adverse events (AEs), but higher systemic AEs than non-frail participants. CONCLUSION: Similar immune responses across vaccine routes warrants further evaluation of intradermal BNT162b2 in frail geriatric populations. Frail participants may be more sensitive to reporting systemic AEs. REGISTRATION OF CLINICAL TRIALS: The parent study was registered under the Thai Clinical Trials Registry (TCTR20220112002).

Asunto(s)

Vacuna BNT162 , Vacunas contra la COVID-19 , COVID-19 , Inmunogenicidad Vacunal , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , Vacuna BNT162/administración & dosificación , Vacuna BNT162/inmunología , ChAdOx1 nCoV-19 , COVID-19/prevención & control , COVID-19/inmunología , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Anciano Frágil , Inmunización Secundaria , Inyecciones Intramusculares , Estudios Prospectivos , Pueblos del Sudeste Asiático , Tailandia

RESUMEN

Vaccine-induced immune thrombocytopenia and thrombosis (VITT) is a newly recognized syndrome mediated by anti-platelet factor 4 antibodies induced by Covid-19 adenovirus-vectored vaccines including ChAdOx1 nCoV-19 and Ad26.COV2.S. This study validated a proposed Brighton Collaboration case definition for VITT. A data collection form was developed and used to capture the variations in VITT criteria and assess their level of diagnostic certainty from adjudicated positive VITT case datasheets in Germany (n = 71), UK (n = 220), Australia (n = 203), and Taiwan (n = 56). We observed high prevalence of each component of the proposed VITT definition in positive cases (84%-100%), except for the occurrence of thrombosis or thromboembolism criterion in only 34% of VITT cases in Taiwan. The sensitivity of this proposed definition was 100% for Germany and UK, 92% for Australia, and 89% for Taiwan cases. These findings support the validity of this case definition for VITT.

Asunto(s)

Vacunas contra la COVID-19 , ChAdOx1 nCoV-19 , Púrpura Trombocitopénica Idiopática , Trombosis , Humanos , Vacunas contra la COVID-19/efectos adversos , Vacunas contra la COVID-19/inmunología , Trombosis/inmunología , Trombosis/etiología , ChAdOx1 nCoV-19/inmunología , ChAdOx1 nCoV-19/efectos adversos , Alemania/epidemiología , Australia/epidemiología , Púrpura Trombocitopénica Idiopática/diagnóstico , Púrpura Trombocitopénica Idiopática/etiología , Púrpura Trombocitopénica Idiopática/inmunología , Púrpura Trombocitopénica Idiopática/inducido químicamente , Púrpura Trombocitopénica Idiopática/epidemiología , Taiwán/epidemiología , Masculino , Persona de Mediana Edad , Femenino , Reino Unido/epidemiología , COVID-19/prevención & control , COVID-19/diagnóstico , COVID-19/inmunología , Adulto , Anciano , Ad26COVS1/efectos adversos , SARS-CoV-2/inmunología , Factor Plaquetario 4/inmunología

RESUMEN

BACKGROUND: To overcome supply issues of COVID-19 vaccines, this partially single blind, multi-centric, vaccine trial aimed to evaluate humoral immunogenicity using lower vaccine doses, intradermal vaccination, and heterologous vaccine schedules. Also, the immunity after a booster vaccination was assessed. METHODOLOGY: 566 COVID-19-naïve healthy adults were randomized to 1 of 8 treatment arms consisting of combinations of BNT162b2, mRNA-1273, and ChAdOx1-S. Anti-Receptor-Binding Domain immunoglobulin G (RBD IgG) titers, neutralizing antibody titres, and avidity of the anti-RBD IgGs was assessed up to 1 year after study start. RESULTS: Prolonging the interval between vaccinations from 28 to 84 days and the use of a heterologous BNT162b2 + mRNA-1273 vaccination schedule led to a non-inferior immune response, compared to the reference schedule. A low dose of mRNA-1273 was sufficient to induce non-inferior immunity. Non-inferiority could not be demonstrated for intradermal vaccination. For all adapted vaccination schedules, anti-RBD IgG titres measured after a first booster vaccination were non-inferior to their reference schedule. CONCLUSION: This study suggests that reference vaccine schedules can be adapted without jeopardizing the development of an adequate immune response. Immunity after a booster vaccination did not depend on the dose or brand of the booster vaccine, which is relevant for future booster campaigns. The trial is registered in the European Union Clinical Trials Register (number 2021-001993-52) and on clinicaltrials.gov (NCT06189040).

Asunto(s)

Anticuerpos Neutralizantes , Anticuerpos Antivirales , Vacuna BNT162 , Vacunas contra la COVID-19 , COVID-19 , Inmunidad Humoral , Esquemas de Inmunización , Inmunización Secundaria , Inmunoglobulina G , SARS-CoV-2 , Humanos , Adulto , Masculino , Femenino , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , SARS-CoV-2/inmunología , COVID-19/prevención & control , COVID-19/inmunología , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Vacuna BNT162/inmunología , Vacuna BNT162/administración & dosificación , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/inmunología , Inmunoglobulina G/sangre , Persona de Mediana Edad , Vacuna nCoV-2019 mRNA-1273/inmunología , Adulto Joven , ChAdOx1 nCoV-19/inmunología , Método Simple Ciego , Inmunogenicidad Vacunal , Voluntarios Sanos , Vacunación/métodos

RESUMEN

Among new vaccine technologies contributed to the control of the COVID-19 pandemic, ChAdOx1 nCoV-19, a chimpanzee adenovirus (ChAd)-vector vaccine expressing the SARS-CoV-2 spike protein, could be administered globally owing to its low production cost and lack of a requirement for frozen storage. Despite its benefits, most recipients have reported immediate inflammatory reactions after the initial dose vaccination. We comprehensively examined the immune landscape following ChAdOx1 nCoV-19 vaccination based on the single-cell transcriptomes of immune cells and epigenomic profiles of monocytes. Monocyte and innate-like activated T cell populations expressing interferon-stimulated genes (ISGs) increased 1 day post-vaccination with appearance of distinct subtype of ISG-activated cells, returning to baseline by day 14. Pre-treatment with oral corticosteroids effectively curtailed these ISG-associated inflammatory responses by decreasing chromatin accessibility of major ISGs, without hampering vaccine immunogenicity. Our findings provide insights into the human immune response following ChAd-based vaccination and propose a method to reduce inflammatory side effects.

Asunto(s)

Vacunas contra la COVID-19 , ChAdOx1 nCoV-19 , Inmunidad Innata , SARS-CoV-2 , Humanos , Vacunas contra la COVID-19/inmunología , ChAdOx1 nCoV-19/inmunología , SARS-CoV-2/inmunología , SARS-CoV-2/genética , COVID-19/prevención & control , COVID-19/inmunología , Corticoesteroides , Glicoproteína de la Espiga del Coronavirus/inmunología , Glicoproteína de la Espiga del Coronavirus/genética , Animales , Vacunación/métodos , Monocitos/inmunología , Inmunogenicidad Vacunal , Vectores Genéticos/genética , Linfocitos T/inmunología , Masculino , Femenino , Adulto

Asunto(s)

ChAdOx1 nCoV-19 , Humanos , Alemania , COVID-19/prevención & control , Vacunación/legislación & jurisprudencia

RESUMEN

Background: In February 2021, a few cases of unusual, severe thrombotic events associated with thrombocytopenia reported after vaccination with ChAdOx1 nCoV-19 (Vaxzevria) or with Johnson & Johnson's Janssen vaccine raise concern about safety. The vaccine-induced thrombotic thrombocytopenia (VITT) has been related to the presence of platelet-activating antibodies directed against platelet Factor 4. Objectives: We investigated VITT subject genetic background by a high-throughput whole exome sequencing (WES) approach in order to investigate VITT genetic predisposition. Methods: Six consecutive patients (females of Caucasian origin with a mean age of 64 years) were referred to the Atherothrombotic Diseases Center (Department of Experimental and Clinical Medicine, Azienda Ospedaliero-Universitaria Careggi, Florence) with a diagnosis of definite VITT underwent WES analysis. WES analysis was performed on the Illumina NextSeq500 platform. Results:WES analysis revealed a total of 140,563 genetic variants. Due to VITT's rare occurrence, we focused attention on rare variants. The global analysis of all high-quality rare variants did not reveal a significant enrichment of mutated genes in biological/functional pathways common to patients analyzed. Afterwards, we focused on rare variants in genes associated with blood coagulation and fibrinolysis, platelet activation and aggregation, integrin-mediated signaling pathway, and inflammation with particular attention to those involved in vascular damage, as well as autoimmune thrombocytopenia. According to ACMG criteria, 47/194 (24.2%) rare variants were classified as uncertain significance variants (VUS), whereas the remaining were likely benign/benign. Conclusion: WES analysis identifies rare variants possibly favoring the prothrombotic state triggered by the exposure to the vaccine. Functional studies and/or extensions to a larger number of patients might allow a more comprehensive definition of these molecular pathways.

Asunto(s)

Secuenciación del Exoma , Humanos , Persona de Mediana Edad , Femenino , Anciano , Trombocitopenia/genética , Trombocitopenia/inducido químicamente , ChAdOx1 nCoV-19/efectos adversos , Trombosis/genética , Predisposición Genética a la Enfermedad , Factor Plaquetario 4/genética , Masculino , Vacunación/efectos adversos

RESUMEN

ChAdOx1-S is a viral vector vaccine developed by AstraZeneca. We aimed to assess the effectiveness of 1 and 2 doses of the ChAdOx1-S vaccine in reducing COVID-19-related in-hospital mortality in individuals with schizophrenia. This is a retrospective cohort study using a nationwide hospital database in Brazil. Individuals diagnosed with COVID-19 and schizophrenia were included in the study. The exposures were 0, 1, and 2 doses of ChAdOx1-S. The outcome of mortality was measured in hazard ratios (HR), calculated using multivariable Cox regression models. The study included 1,929 positive cases of COVID-19 in schizophrenia patients. After adjusting for age, socioeconomic factors, and comorbidities, we observed a significant 55% decrease in the hazard of mortality in the 2-dose vaccination group (HR 0.45, 95% CI: 0.310-0.652) compared to the unvaccinated. Surprisingly, our results did not show any significant reduction in the hazard of mortality in the 1 dose vaccination group (HR 1.278, 95% CI: 0.910-1.795). The effectiveness of two doses of ChAdOx1-S in individuals with schizophrenia aligns with findings from studies on the general population. That one dose was insignificant. Overall, these findings are important for informing public health decisions - prioritizing individuals with schizophrenia for vaccinations and managing acceptance of vaccines.

Asunto(s)

COVID-19 , Mortalidad Hospitalaria , Esquizofrenia , Humanos , Estudios Retrospectivos , Esquizofrenia/mortalidad , COVID-19/prevención & control , COVID-19/mortalidad , Masculino , Femenino , Persona de Mediana Edad , Adulto , Brasil/epidemiología , SARS-CoV-2/inmunología , ChAdOx1 nCoV-19 , Anciano , Vacunación , Eficacia de las Vacunas , Vacunas contra la COVID-19/administración & dosificación , Vacunas contra la COVID-19/inmunología

RESUMEN

Understanding SARS-CoV-2 vaccine-induced antibody responses in varied antigenic and serological prior exposures can guide optimal vaccination strategies for enhanced immunogenicity. We evaluated spike (S)-directed IgG, IgM, and IgA antibody optical densities (ODs) and concentrations to the two-dose ChAdOx1-S Oxford-AstraZeneca (ChAdOx1-S, Covishield) SARS-CoV-2 vaccine in 67 Ugandans, categorised by prior infection and baseline S-IgG histories: uninfected and S-IgG-negative (n = 12); previously infected yet S-IgG-negative (n = 17); and previously infected with S-IgG-positive status (n = 38). Antibody dynamics were compared across eight timepoints from baseline till nine months. S-IgG antibodies remained consistently potent across all groups. Individuals with prior infections maintained robust S-IgG levels, underscoring the endurance of hybrid immunity. In contrast, those without prior exposure experienced an initial surge in S-IgG after the primary dose but no subsequent significant increase post-boost. However, they reached levels parallel to the previously exposed groups. S-IgM levels remained moderate, while S-IgA persisted in individuals with prior antigen exposure. ChAdOx1-S, Covishield vaccine elicited robust and sustained antibody responses in recipients, irrespective of their initial immune profiles. Hybrid immunity showed higher responses, aligning with global observations. Early post-vaccination antibody levels could predict long-term immunity, particularly in individuals without virus exposure. These findings can inform vaccine strategies and pandemic management.

Asunto(s)

Anticuerpos Antivirales , Vacunas contra la COVID-19 , COVID-19 , ChAdOx1 nCoV-19 , Inmunoglobulina G , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Humanos , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , COVID-19/inmunología , COVID-19/prevención & control , SARS-CoV-2/inmunología , Masculino , Femenino , Adulto , ChAdOx1 nCoV-19/inmunología , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Glicoproteína de la Espiga del Coronavirus/inmunología , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Formación de Anticuerpos/inmunología , Persona de Mediana Edad , Adulto Joven , Inmunoglobulina M/sangre , Inmunoglobulina M/inmunología , Inmunoglobulina A/sangre , Inmunoglobulina A/inmunología , Vacunación , Pueblo de África Oriental

RESUMEN

n/a.

Asunto(s)

Vacunas contra la COVID-19 , COVID-19 , ChAdOx1 nCoV-19 , SARS-CoV-2 , Humanos , COVID-19/prevención & control , SARS-CoV-2/inmunología , Vacunas contra la COVID-19/inmunología , Nepal , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Inmunidad Humoral , Vacunas de Productos Inactivados