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1.
J Exp Med ; 220(1)2023 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-36342455

RESUMO

Inborn and acquired deficits of type I interferon (IFN) immunity predispose to life-threatening COVID-19 pneumonia. We longitudinally profiled the B cell response to mRNA vaccination in SARS-CoV-2 naive patients with inherited TLR7, IRF7, or IFNAR1 deficiency, as well as young patients with autoantibodies neutralizing type I IFNs due to autoimmune polyendocrine syndrome type-1 (APS-1) and older individuals with age-associated autoantibodies to type I IFNs. The receptor-binding domain spike protein (RBD)-specific memory B cell response in all patients was quantitatively and qualitatively similar to healthy donors. Sustained germinal center responses led to accumulation of somatic hypermutations in immunoglobulin heavy chain genes. The amplitude and duration of, and viral neutralization by, RBD-specific IgG serological response were also largely unaffected by TLR7, IRF7, or IFNAR1 deficiencies up to 7 mo after vaccination in all patients. These results suggest that induction of type I IFN is not required for efficient generation of a humoral response against SARS-CoV-2 by mRNA vaccines.


Assuntos
Linfócitos B , Vacinas contra COVID-19 , COVID-19 , Interferon Tipo I , Humanos , Anticorpos Neutralizantes , Anticorpos Antivirais , Autoanticorpos , COVID-19/imunologia , COVID-19/prevenção & controle , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus/genética , Receptor 7 Toll-Like/genética , Vacinação , Vacinas de mRNA , Vacinas contra COVID-19/imunologia , Linfócitos B/imunologia , Interferon Tipo I/deficiência
2.
J Clin Invest ; 132(19)2022 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-36189797

RESUMO

The SARS-CoV-2 vaccine NVX-CoV2373 is a protein-based vaccine that might circumvent the difficulties in distributing mRNA vaccines to regions with limited access to cold-chain and refrigeration. However, the NVX-CoV2373-induced T cell and antibody responses remain poorly understood. In this issue of the JCI, Moderbacher et al. characterized SARS-CoV-2-specific CD4+ and CD8+ T cell responses elicited by one or two doses of NVX-CoV2373 in individuals enrolled in a phase I/IIa trial. Substantially increased spike-specific CD4+ and T follicular helper cells were found after the first or second vaccine dose, with some individuals developing a modest spike-specific CD8+ T cell response. Correlation analysis revealed an association between spike-specific CD4+ T cells and neutralizing antibody titers. Notably, preexisting T cell immunity showed negligible effects on NVX-CoV2373-induced T cell responses. These findings indicate that the protein-based vaccine NVX-CoV2373 induces robust T cell immunity capable of recognizing SARS-CoV-2 antigens and supporting humoral immune responses.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19/prevenção & controle , Vacinas contra COVID-19/imunologia , Ensaios Clínicos Fase I como Assunto , Ensaios Clínicos Fase II como Assunto , Humanos , Imunidade Humoral , SARS-CoV-2/imunologia
3.
Medicina (B Aires) ; 82(5): 631-640, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36220018

RESUMO

INTRODUCTION: Given the vulnerability of chronic kidney disease individuals to SARS-CoV-2, nephrology societies have issued statements calling for prioritization of these patients for vaccination. It is not yet known whether COVID-19 vaccines grant the same high level of protection in patients with kidney disease compared to the non-dialysis population. The aims of this study were to evaluate the safety - measured by the adverse events potentially attributed to vaccines (ESAVI) - and the effectiveness - evaluated by the presence of antibodies - in dialysis patients immunized with the COVID-19 Sputnik V vaccine. METHODS: multicenter, observational and analytical study of a prospective cohort of hemodialysis patients from the Ciudad Autónoma de Buenos Aires participating in an official vaccination program. Dialysis requiring individuals older than 18 years, who received both components of the COVID-19 vaccine were included. RESULTS: Data from 491 patients were included in the safety analysis. ESAVI with either the first or second component was detected in 186 (37.9%, 95% CI 33.6%-42.3%). Effectiveness analysis measuring antibodies levels against SARS-CoV-2 were performed in 102 patients; 98% presented these IgG antibodies at day 21 after the second component. In patients with COVID-19 prior to vaccination, antibodies at day 21 after the first component reached almost the highest levels compared to patients without previous COVID-19, but IgG rise among patients with previous COVID-19 was lower than in those without this previous disease. CONCLUSION: The Sputnik V vaccine has been shown to be safe and effective in this patient's population.


Introducción: Dada la vulnerabilidad al SARS-CoV-2 de las personas con enfermedad renal crónica, las sociedades de nefrología han emitido declaraciones pidiendo priorizar a estos pacientes para la vacunación. Aún no se sabe si las vacunas COVID-19 confieren el mismo nivel de protección en pacientes con enfermedad renal. Los objetivos de este estudio fueron evaluar la seguridad, medida por eventos supuestamente atribuidos a las vacunas (ESAVI) y la efectividad, evaluada por la presencia de anticuerpos en pacientes en diálisis inmunizados con la vacuna COVID-19 Sputnik V. Métodos: estudio multicéntrico, observacional y analítico de una cohorte prospectiva de pacientes en hemodiálisis, en la Ciudad Autónoma de Buenos Aires, con plan de vacunación. Se incluyeron pacientes mayores de 18 años en diálisis que recibieron ambos componentes de la vacuna COVID-19. Resultados: 491 pacientes fueron incluidos en el análisis de seguridad. Se detectó ESAVI con el primer o el segundo componente en 186 (37.9% IC 95%: 33.6%-42.3%). La efectividad medida por presencia de anticuerpos IgG contra SARS-Cov-2 se realizó en 102 pacientes, 98% presentaba IgG contra SARS-CoV-2, 21 días después del segundo componente. En pacientes con COVID-19 previo a la vacunación, los anticuerpos al día 21 del primer componente alcanzaron niveles casi mayores que en aquellos que no habían sufrido COVID-19, aunque el aumento de los niveles a los 21 días del segundo componente fue menor que en los pacientes sin COVID-19 previo. Conclusión: Los pacientes en diálisis constituyen una población vulnerable para la infección por SARS-CoV-2, por lo tanto, más allá de las recomendaciones implementadas por las unidades de diálisis, la vacunación completa es mandatoria. Se ha demostrado que la vacuna Sputnik V es segura y eficaz en esta población de pacientes.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Insuficiência Renal Crônica , Eficácia de Vacinas , Humanos , Anticorpos Antivirais , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Vacinas contra COVID-19/imunologia , Imunoglobulina G , Estudos Prospectivos , Diálise Renal , SARS-CoV-2 , Vacinas de Produtos Inativados , Insuficiência Renal Crônica/complicações , Argentina
4.
J Clin Virol ; 157: 105321, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36279695

RESUMO

BACKGROUND: The NVX-CoV2373-vaccine has recently been licensed, although knowledge on vaccine-induced humoral and cellular immunity towards the parental strain and variants of concern (VOCs) in comparison to mRNA-regimens is limited. METHODS: In this observational study, 66 individuals were recruited to compare immunogenicity and reactogenicity of NVX-CoV2373 with BNT162b2 or mRNA-1273. Vaccine-induced antibodies were analyzed using ELISA and neutralization assays, specific CD4 and CD8 T-cells were characterized based on intracellular cytokine staining using flow-cytometry after antigen-specific stimulation with parental spike or VOCs. RESULTS: Two doses of NVX-CoV2373 strongly induced anti-spike IgG, although IgG-levels were lower than after vaccination with BNT162b2 or mRNA-1273 (p = 0.006). Regardless of the vaccine and despite different IgG-levels, neutralizing activity towards VOCs was highest for Delta, followed by BA.2 and BA.1. The protein-based vaccine failed to induce any spike-specific CD8 T-cells which were detectable in 3/22 (14%) individuals only. In contrast, spike-specific CD4 T-cells were induced in 18/22 (82%) individuals, although their levels were lower (p<0.001), had lower CTLA-4 expression (p<0.0001) and comprised less multifunctional cells co-expressing IFNγ, TNFα and IL-2 (p = 0.0007). Unlike neutralizing antibodies, NVX-CoV2373-induced CD4 T-cells equally recognized all tested VOCs from Alpha to Omicron. In individuals with a history of infection, one dose of NVX-CoV2373 had similar immunogenicity as two doses in non-infected individuals. The vaccine was overall well tolerated. CONCLUSION: NVX-CoV2373 strongly induced spike-specific antibodies and CD4 T-cells, albeit at lower levels as mRNA-regimens. Cross-reactivity of CD4 T-cells towards the parental strain and all tested VOCs may hold promise to protect from severe disease.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Humanos , Vacina de mRNA-1273 contra 2019-nCoV , Anticorpos Neutralizantes , Anticorpos Antivirais , Vacina BNT162 , COVID-19/prevenção & controle , Imunidade Humoral , Imunoglobulina G , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Vacinação , Vacinas contra COVID-19/imunologia
5.
Front Immunol ; 13: 985938, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36268023

RESUMO

This proof-of-concept study tested if prior BCG revaccination can qualitatively and quantitively enhance antibody and T-cell responses induced by Oxford/AstraZeneca ChAdOx1nCoV-19 or COVISHIELD™, an efficacious and the most widely distributed vaccine in India. We compared COVISHIELD™ induced longitudinal immune responses in 21 BCG re-vaccinees (BCG-RV) and 13 BCG-non-revaccinees (BCG-NRV), all of whom were BCG vaccinated at birth; latent tuberculosis negative and SARS-CoV-2 seronegative prior to COVISHIELD™ vaccination. Compared to BCG-NRV, BCG-RV displayed significantly higher and persistent spike-specific neutralizing (n) Ab titers and polyfunctional CD4+ and CD8+ T-cells for eight months post COVISHIELD™ booster, including distinct CD4+IFN-γ+ and CD4+IFN-γ- effector memory (EM) subsets co-expressing IL-2, TNF-α and activation induced markers (AIM) CD154/CD137 as well as CD8+IFN-γ+ EM,TEMRA (T cell EM expressing RA) subset combinations co-expressing TNF-α and AIM CD137/CD69. Additionally, elevated nAb and T-cell responses to the Delta mutant in BCG-RV highlighted greater immune response breadth. Mechanistically, these BCG adjuvant effects were associated with elevated markers of trained immunity, including higher IL-1ß and TNF-α expression in CD14+HLA-DR+monocytes and changes in chromatin accessibility highlighting BCG-induced epigenetic changes. This study provides first in-depth analysis of both antibody and memory T-cell responses induced by COVISHIELD™ in SARS-CoV-2 seronegative young adults in India with strong evidence of a BCG-induced booster effect and therefore a rational basis to validate BCG, a low-cost and globally available vaccine, as an adjuvant to enhance heterologous adaptive immune responses to current and emerging COVID-19 vaccines.


Assuntos
Vacina BCG , Vacinas contra COVID-19 , COVID-19 , Humanos , Adulto Jovem , Adjuvantes Imunológicos , Cromatina , COVID-19/prevenção & controle , Vacinas contra COVID-19/imunologia , Imunidade , Interleucina-2 , SARS-CoV-2 , Fator de Necrose Tumoral alfa , Vacinação
6.
RMD Open ; 8(2)2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36216409

RESUMO

BACKGROUND: Several health authorities recommend a third (booster) vaccination to protect patients with rheumatic and musculoskeletal diseases from severe COVID-19. Methotrexate has been shown to reduce the efficacy of the first and second dose of SARS-CoV-2 mRNA vaccines. So far, it remains unknown how concomitant methotrexate affects the efficacy of a COVID-19 booster vaccination. METHODS: We compared the humoral immune response to SARS-CoV-2 vaccination in 136 patients with rheumatoid arthritis (RA) treated with methotrexate and/or biological or targeted synthetic (b/tsDMARDs). IgG targeting the receptor binding domain (RBD) of SARS-CoV-2 spike protein was measured at a median of 52.5 (range 2-147) days after a third dose of the SARS-CoV-2 mRNA vaccines BNT162b2 or mRNA-1273. RESULTS: Anti-RBD IgG was significantly reduced in elderly patients receiving concomitant treatment with methotrexate as compared with elderly patients receiving monotherapy with b/tsDMARDs or methotrexate (64.8 (20.8, 600.3) binding antibody units per mL (BAU/mL) vs 1106.0 (526.3, 4965.2) BAU/mL vs 1743.8 (734.5, 6779.6) BAU/mL, median (IQR), p<0.001, Kruskal-Wallis test). In younger patients (< 64.5 years), concomitant methotrexate had no significant impact on the humoral immune response. CONCLUSIONS: Concomitant methotrexate increases the risk of an insufficient humoral immune response to SARS-CoV-2 vaccination in elderly patients with RA. Pausing methotrexate during the third vaccination period may be considered for this group of patients.


Assuntos
Artrite Reumatoide , Vacinas contra COVID-19 , COVID-19 , Imunidade Humoral , Metotrexato , Idoso , Anticorpos Antivirais , Artrite Reumatoide/tratamento farmacológico , Vacina BNT162 , COVID-19/prevenção & controle , Vacinas contra COVID-19/imunologia , Humanos , Imunoglobulina G , Metotrexato/uso terapêutico , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus
7.
Science ; 378(6622): eabo2523, 2022 11 25.
Artigo em Inglês | MEDLINE | ID: mdl-36302057

RESUMO

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has highlighted the need for vaccines that not only prevent disease but also prevent transmission. Parenteral vaccines induce robust systemic immunity but poor immunity at the respiratory mucosa. We developed a vaccine strategy that we call "prime and spike," which leverages existing immunity generated by primary vaccination (prime) to elicit mucosal immune memory within the respiratory tract by using unadjuvanted intranasal spike boosters (spike). We show that prime and spike induces robust resident memory B and T cell responses, induces immunoglobulin A at the respiratory mucosa, boosts systemic immunity, and completely protects mice with partial immunity from lethal SARS-CoV-2 infection. Using divergent spike proteins, prime and spike enables the induction of cross-reactive immunity against sarbecoviruses.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Imunidade nas Mucosas , Memória Imunológica , Células B de Memória , Células T de Memória , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Animais , Camundongos , Administração Intranasal , Anticorpos Antivirais , COVID-19/prevenção & controle , COVID-19/transmissão , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Vacinação/métodos , Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/imunologia , Imunoglobulina A , Células B de Memória/imunologia , Células T de Memória/imunologia
8.
Cell Mol Immunol ; 19(11): 1279-1289, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36220993

RESUMO

The rapid mutation and spread of SARS-CoV-2 variants urge the development of effective mucosal vaccines to provide broad-spectrum protection against the initial infection and thereby curb the transmission potential. Here, we designed a chimeric triple-RBD immunogen, 3Ro-NC, harboring one Delta RBD and two Omicron RBDs within a novel protein scaffold. 3Ro-NC elicits potent and broad RBD-specific neutralizing immunity against SARS-CoV-2 variants of concern. Notably, intranasal immunization with 3Ro-NC plus the mucosal adjuvant KFD (3Ro-NC + KFDi.n) elicits coordinated mucosal IgA and higher neutralizing antibody specificity (closer antigenic distance) against the Omicron variant. In Omicron-challenged human ACE2 transgenic mice, 3Ro-NC + KFDi.n immunization significantly reduces the tissue pathology in the lung and lowers the viral RNA copy numbers in both the lung (85.7-fold) and the nasal turbinate (13.6-fold). Nasal virologic control is highly correlated with RBD-specific secretory IgA antibodies. Our data show that 3Ro-NC plus KFD is a promising mucosal vaccine candidate for protection against SARS-CoV-2 Omicron infection, pathology and transmission potential.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Animais , Humanos , Camundongos , Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19/prevenção & controle , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus/genética , Vacinas contra COVID-19/imunologia , Imunidade nas Mucosas , Administração Intranasal
9.
PLoS Med ; 19(10): e1003979, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36301821

RESUMO

BACKGROUND: Vaccines can be less immunogenic in people living with HIV (PLWH), but for SARS-CoV-2 vaccinations this is unknown. In this study we set out to investigate, for the vaccines currently approved in the Netherlands, the immunogenicity and reactogenicity of SARS-CoV-2 vaccinations in PLWH. METHODS AND FINDINGS: We conducted a prospective cohort study to examine the immunogenicity of BNT162b2, mRNA-1273, ChAdOx1-S, and Ad26.COV2.S vaccines in adult PLWH without prior COVID-19, and compared to HIV-negative controls. The primary endpoint was the anti-spike SARS-CoV-2 IgG response after mRNA vaccination. Secondary endpoints included the serological response after vector vaccination, anti-SARS-CoV-2 T-cell response, and reactogenicity. Between 14 February and 7 September 2021, 1,154 PLWH (median age 53 [IQR 44-60] years, 85.5% male) and 440 controls (median age 43 [IQR 33-53] years, 28.6% male) were included in the final analysis. Of the PLWH, 884 received BNT162b2, 100 received mRNA-1273, 150 received ChAdOx1-S, and 20 received Ad26.COV2.S. In the group of PLWH, 99% were on antiretroviral therapy, 97.7% were virally suppressed, and the median CD4+ T-cell count was 710 cells/µL (IQR 520-913). Of the controls, 247 received mRNA-1273, 94 received BNT162b2, 26 received ChAdOx1-S, and 73 received Ad26.COV2.S. After mRNA vaccination, geometric mean antibody concentration was 1,418 BAU/mL in PLWH (95% CI 1322-1523), and after adjustment for age, sex, and vaccine type, HIV status remained associated with a decreased response (0.607, 95% CI 0.508-0.725, p < 0.001). All controls receiving an mRNA vaccine had an adequate response, defined as >300 BAU/mL, whilst in PLWH this response rate was 93.6%. In PLWH vaccinated with mRNA-based vaccines, higher antibody responses were predicted by CD4+ T-cell count 250-500 cells/µL (2.845, 95% CI 1.876-4.314, p < 0.001) or >500 cells/µL (2.936, 95% CI 1.961-4.394, p < 0.001), whilst a viral load > 50 copies/mL was associated with a reduced response (0.454, 95% CI 0.286-0.720, p = 0.001). Increased IFN-γ, CD4+ T-cell, and CD8+ T-cell responses were observed after stimulation with SARS-CoV-2 spike peptides in ELISpot and activation-induced marker assays, comparable to controls. Reactogenicity was generally mild, without vaccine-related serious adverse events. Due to the control of vaccine provision by the Dutch National Institute for Public Health and the Environment, there were some differences between vaccine groups in the age, sex, and CD4+ T-cell counts of recipients. CONCLUSIONS: After vaccination with BNT162b2 or mRNA-1273, anti-spike SARS-CoV-2 antibody levels were reduced in PLWH compared to HIV-negative controls. To reach and maintain the same serological responses as HIV-negative controls, additional vaccinations are probably required. TRIAL REGISTRATION: The trial was registered in the Netherlands Trial Register (NL9214). https://www.trialregister.nl/trial/9214.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Infecções por HIV , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ad26COVS1 , Anticorpos Antivirais , Vacina BNT162 , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/imunologia , Infecções por HIV/imunologia , Imunogenicidade da Vacina , Imunoglobulina G , Países Baixos/epidemiologia , Estudos Prospectivos , RNA Mensageiro , SARS-CoV-2
10.
Viruses ; 14(10)2022 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-36298854

RESUMO

Solid organ transplant recipients (SOTRs) show higher rates of COVID-19 breakthrough infection than the general population, and nowadays, vaccination is the key preventative strategy. Nonetheless, SOTRs show lower vaccine efficacy for the prevention of severe COVID-19. Moreover, the emergence of new SARS-CoV-2 variants of concern has highlighted the need to improve vaccine-induced immune responses by the administration of repeated booster doses. In this study, we analyzed the humoral and cellular responses in a cohort of 25 SOTRs, including 15 never-infected SOTRs who received the fourth dose of the mRNA vaccine and 10 SOTRs who contracted SARS-CoV-2 infection after the third dose. We analyzed the serum IgG and IgA levels through CLIA or ELISA, respectively, and the Spike-specific T cells by ELISpot assay. We report a significant increase in anti-Spike IgG and no differences in IgA secretion in both groups of patients before and after the booster dose or the natural infection. Still, we show higher IgA levels in recovered SOTRs compared to the fourth dose recipients. Conversely, we show the maintenance of a positive Spike-specific T-cell response in SOTRs who received the fourth dose, which, instead, was significantly increased in SOTRs who contracted the infection. Our results suggest that the booster, either through the fourth dose or natural infection, in vulnerable poor responder SOTRs, improves both humoral and cellular-specific immune responses against SARS-CoV-2.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Transplantados , Humanos , Anticorpos Antivirais , COVID-19/epidemiologia , COVID-19/imunologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/imunologia , Imunidade , Imunoglobulina A , Imunoglobulina G , Transplante de Órgãos/efeitos adversos , SARS-CoV-2
12.
Viruses ; 14(10)2022 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-36298743

RESUMO

A preliminary vaccination trial against the emergent pathogen, SARS-CoV-2, was completed in captive black-footed ferrets (Mustela nigripes; BFF) to assess safety, immunogenicity, and anti-viral efficacy. Vaccination and boosting of 15 BFF with purified SARS-CoV-2 S1 subunit protein produced a nearly 150-fold increase in mean antibody titers compared to pre-vaccination titers. Serum antibody responses were highest in young animals, but in all vaccinees, antibody response declined rapidly. Anti-viral activity from vaccinated and unvaccinated BFF was determined in vitro, as well as in vivo with a passive serum transfer study in mice. Transgenic mice that received BFF serum transfers and were subsequently challenged with SARS-CoV-2 had lung viral loads that negatively correlated (p < 0.05) with the BFF serum titer received. Lastly, an experimental challenge study in a small group of BFF was completed to test susceptibility to SARS-CoV-2. Despite viral replication and shedding in the upper respiratory tract for up to 7 days post-challenge, no clinical disease was observed in either vaccinated or naive animals. The lack of morbidity or mortality observed indicates SARS-CoV-2 is unlikely to affect wild BFF populations, but infected captive animals pose a potential risk, albeit low, for humans and other animals.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Animais , Anticorpos Antivirais , Antivirais , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Vacinas contra COVID-19/imunologia , Furões , SARS-CoV-2
13.
Cell Rep Med ; 3(10): 100781, 2022 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-36240755

RESUMO

Patients with blood cancer continue to have a greater risk of inadequate immune responses following three COVID-19 vaccine doses and risk of severe COVID-19 disease. In the context of the CAPTURE study (NCT03226886), we report immune responses in 80 patients with blood cancer who received a fourth dose of BNT162b2. We measured neutralizing antibody titers (NAbTs) using a live virus microneutralization assay against wild-type (WT), Delta, and Omicron BA.1 and BA.2 and T cell responses against WT and Omicron BA.1 using an activation-induced marker (AIM) assay. The proportion of patients with detectable NAb titers and T cell responses after the fourth vaccine dose increased compared with that after the third vaccine dose. Patients who received B cell-depleting therapies within the 12 months before vaccination have the greatest risk of not having detectable NAbT. In addition, we report immune responses in 57 patients with breakthrough infections after vaccination.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Neoplasias , Humanos , Anticorpos Neutralizantes , Anticorpos Antivirais , Vacina BNT162 , Estudos Clínicos como Assunto , COVID-19/prevenção & controle , Vacinas contra COVID-19/imunologia , Imunidade , SARS-CoV-2
16.
N Engl J Med ; 387(14): 1279-1291, 2022 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-36112399

RESUMO

BACKGROUND: The safety and immunogenicity of the bivalent omicron-containing mRNA-1273.214 booster vaccine are not known. METHODS: In this ongoing, phase 2-3 study, we compared the 50-µg bivalent vaccine mRNA-1273.214 (25 µg each of ancestral Wuhan-Hu-1 and omicron B.1.1.529 [BA.1] spike messenger RNAs) with the previously authorized 50-µg mRNA-1273 booster. We administered mRNA-1273.214 or mRNA-1273 as a second booster in adults who had previously received a two-dose (100-µg) primary series and first booster (50-µg) dose of mRNA-1273 (≥3 months earlier). The primary objectives were to assess the safety, reactogenicity, and immunogenicity of mRNA-1273.214 at 28 days after the booster dose. RESULTS: Interim results are presented. Sequential groups of participants received 50 µg of mRNA-1273.214 (437 participants) or mRNA-1273 (377 participants) as a second booster dose. The median time between the first and second boosters was similar for mRNA-1273.214 (136 days) and mRNA-1273 (134 days). In participants with no previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the geometric mean titers of neutralizing antibodies against the omicron BA.1 variant were 2372.4 (95% confidence interval [CI], 2070.6 to 2718.2) after receipt of the mRNA-1273.214 booster and 1473.5 (95% CI, 1270.8 to 1708.4) after receipt of the mRNA-1273 booster. In addition, 50-µg mRNA-1273.214 and 50-µg mRNA-1273 elicited geometric mean titers of 727.4 (95% CI, 632.8 to 836.1) and 492.1 (95% CI, 431.1 to 561.9), respectively, against omicron BA.4 and BA.5 (BA.4/5), and the mRNA-1273.214 booster also elicited higher binding antibody responses against multiple other variants (alpha, beta, gamma, and delta) than the mRNA-1273 booster. Safety and reactogenicity were similar with the two booster vaccines. Vaccine effectiveness was not assessed in this study; in an exploratory analysis, SARS-CoV-2 infection occurred in 11 participants after the mRNA-1273.214 booster and in 9 participants after the mRNA-1273 booster. CONCLUSIONS: The bivalent omicron-containing vaccine mRNA-1273.214 elicited neutralizing antibody responses against omicron that were superior to those with mRNA-1273, without evident safety concerns. (Funded by Moderna; ClinicalTrials.gov number, NCT04927065.).


Assuntos
Vacinas contra COVID-19 , COVID-19 , Imunização Secundária , Vacinas Combinadas , Vacinas de mRNA , Vacina de mRNA-1273 contra 2019-nCoV/imunologia , Vacina de mRNA-1273 contra 2019-nCoV/uso terapêutico , Adulto , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , COVID-19/imunologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/uso terapêutico , Humanos , Imunogenicidade da Vacina/imunologia , SARS-CoV-2 , Vacinas Combinadas/imunologia , Vacinas Combinadas/uso terapêutico , Vacinas de mRNA/imunologia , Vacinas de mRNA/uso terapêutico
17.
Trials ; 23(1): 780, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36109788

RESUMO

Kidney transplant recipients are at an increased risk of severe COVID-19-associated hospitalisation and death. Vaccination has been a key public health strategy to reduce disease severity and infectivity, but the effectiveness of COVID vaccines is markedly reduced in kidney transplant recipients. Urgent strategies to enhance vaccine efficacy are needed. METHODS: RIVASTIM-rapamycin is a multicentre, randomised, controlled trial examining the effect of immunosuppression modification prior to a third dose of COVID-19 vaccine in kidney transplant recipients who have failed to develop protective immunity to a 2-dose COVID-19 vaccine schedule. Participants will be randomised 1:1 to either remain on standard of care immunosuppression with tacrolimus, mycophenolate, and prednisolone (control) or cease mycophenolate and commence sirolimus (intervention) for 4 weeks prior to and following vaccination. The primary outcome is the proportion of participants in each trial arm who develop protective serological neutralisation of live SARS-CoV-2 virus at 4-6 weeks following a third COVID-19 vaccination. Secondary outcomes include SARS-CoV-receptor binding domain IgG, vaccine-specific immune cell populations and responses, and the safety and tolerability of sirolimus switch. DISCUSSION: Immunosuppression modification strategies may improve immunological vaccine response. We hypothesise that substituting the mTOR inhibitor sirolimus for mycophenolate in a triple drug regimen will enhance humoral and cell-mediated responses to COVID vaccination for kidney transplant recipients. TRIAL REGISTRATION: Australia New Zealand Clinical Trials Registry ACTRN12621001412820. Registered on 20 October 2021; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=382891&isReview=true.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Imunossupressores , Transplante de Rim , COVID-19/prevenção & controle , Vacinas contra COVID-19/imunologia , Humanos , Imunoglobulina G , Terapia de Imunossupressão , Imunossupressores/efeitos adversos , Inulina , Transplante de Rim/efeitos adversos , Estudos Multicêntricos como Assunto , Prednisolona , Ensaios Clínicos Controlados Aleatórios como Assunto , SARS-CoV-2 , Sirolimo/efeitos adversos , Serina-Treonina Quinases TOR , Tacrolimo
18.
Nat Commun ; 13(1): 5135, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-36050304

RESUMO

Immune responses at the respiratory mucosal interface are critical to prevent respiratory infections but it is unclear to what extent antigen specific mucosal secretory IgA (SIgA) antibodies are induced by mRNA vaccination in humans. Here we analyze paired serum and saliva samples from patients with and without prior coronavirus disease 2019 (COVID-19) at multiple time points pre and post severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccination. Our results suggest mucosal SIgA responses induced by mRNA vaccination are impacted by pre-existing immunity. Indeed, vaccination induced a minimal mucosal SIgA response in individuals without pre-exposure to SARS-CoV-2 while SIgA induction after vaccination was more efficient in patients with a history of COVID-19.


Assuntos
Vacinas contra COVID-19 , COVID-19 , SARS-CoV-2 , Anticorpos Antivirais , Formação de Anticorpos , COVID-19/imunologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/imunologia , Humanos , Imunoglobulina A Secretora , RNA Mensageiro , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus , Vacinação
19.
Allergy Asthma Proc ; 43(5): 419-430, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36065108

RESUMO

Background: Secretory immunoglobulin A (sIgA) plays an important role in antiviral protective immunity. Although salivary testing has been used for many viral infections, including severe acute respiratory syndrome (SARS) and Middle East Respiratory Syndrome (MERS), its use has not yet been well established with the SARS coronavirus 2 (SARS-CoV-2). Quantification of salivary IgA and IgG antibodies can elucidate mucosal and systemic immune responses after natural infection or vaccination. Here, we report the development and validation of a rapid enzyme-linked immunosorbent assay (ELISA) for anti-SARS-CoV-2 salivary IgA and serum IgG antibodies, and present quantitative results for immunized subjects both prior to or following COVID-19 infections. Objective: Total and serum SARS-CoV-2 spike-specific IgG responses were compared with salivary spike-specific IgA and IgG responses in samples obtained from patients recently infected with SARS-CoV-2 and from subjects recently immunized with COVID-19 vaccines. Methods: A total of 52 paired saliva and serum samples were collected from 26 study participants: 7 subjects after COVID-19 infection and 19 subjects who were uninfected. The ELISA results from these samples were compared with five prepandemic control serum samples. Total IgG and SARS-CoV-2 spike-specific IgG in the serum samples from the subjects who were infected and vaccinated were also measured in a commercial laboratory with an enzyme immunoassay. Results: A wide variation in antibody responses was seen in salivary and serum samples measured by both methods. Three groups of serum total and IgG spike-specific SARS-CoV-2 antibody responses were observed: (1) low, (2) intermediate, and (3) high antibody responders. A correlational analysis of salivary IgA (sIgA) responses with serum IgG concentrations showed a statistical correlation in the low and intermediate antibody responder groups but not in the high group (which we believe was a result of saturation). Conclusion: These preliminary findings suggest measuring salivary and serum IgG and IgA merit further investigation as markers of current or recent SARS-CoV-2 infections.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Imunoglobulina A , Imunoglobulina G , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Anticorpos Antivirais , COVID-19/sangue , COVID-19/imunologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/imunologia , Humanos , Imunização , Imunoglobulina A/análise , Imunoglobulina A/sangue , Imunoglobulina A/imunologia , Imunoglobulina A Secretora , Imunoglobulina G/análise , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Saliva/química , Saliva/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Vacinação
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