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1.
Elife ; 122024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38716629

RESUMO

SARS-CoV-2 vaccines have been used worldwide to combat COVID-19 pandemic. To elucidate the factors that determine the longevity of spike (S)-specific antibodies, we traced the characteristics of S-specific T cell clonotypes together with their epitopes and anti-S antibody titers before and after BNT162b2 vaccination over time. T cell receptor (TCR) αß sequences and mRNA expression of the S-responded T cells were investigated using single-cell TCR- and RNA-sequencing. Highly expanded 199 TCR clonotypes upon stimulation with S peptide pools were reconstituted into a reporter T cell line for the determination of epitopes and restricting HLAs. Among them, we could determine 78 S epitopes, most of which were conserved in variants of concern (VOCs). After the 2nd vaccination, T cell clonotypes highly responsive to recall S stimulation were polarized to follicular helper T (Tfh)-like cells in donors exhibiting sustained anti-S antibody titers (designated as 'sustainers'), but not in 'decliners'. Even before vaccination, S-reactive CD4+ T cell clonotypes did exist, most of which cross-reacted with environmental or symbiotic microbes. However, these clonotypes contracted after vaccination. Conversely, S-reactive clonotypes dominated after vaccination were undetectable in pre-vaccinated T cell pool, suggesting that highly responding S-reactive T cells were established by vaccination from rare clonotypes. These results suggest that de novo acquisition of memory Tfh-like cells upon vaccination may contribute to the longevity of anti-S antibody titers.


Assuntos
Anticorpos Antivirais , Vacina BNT162 , Vacinas contra COVID-19 , COVID-19 , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Vacinação , Humanos , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/sangue , Glicoproteína da Espícula de Coronavírus/imunologia , SARS-CoV-2/imunologia , COVID-19/imunologia , COVID-19/prevenção & controle , Vacina BNT162/imunologia , Vacina BNT162/administração & dosagem , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , Feminino , Masculino , Epitopos de Linfócito T/imunologia , Adulto , Linfócitos T Auxiliares-Indutores/imunologia , Pessoa de Meia-Idade
2.
PLoS One ; 19(5): e0303244, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38728294

RESUMO

To predict protective immunity to SARS-CoV-2, cellular immunity seems to be more sensitive than humoral immunity. Through an Interferon-Gamma (IFN-γ) Release Assay (IGRA), we show that, despite a marked decrease in total antibodies, 94.3% of 123 healthcare workers have a positive cellular response 6 months after inoculation with the 2nd dose of BNT162b2 vaccine. Despite the qualitative relationship found, we did not observe a quantitative correlation between IFN-γ and IgG levels against SARS-CoV-2. Using stimulated whole blood from a subset of participants, we confirmed the specific T-cell response to SARS-CoV-2 by dosing elevated levels of the IL-6, IL-10 and TNF-α. Through a 20-month follow-up, we found that none of the infected participants had severe COVID-19 and that the first positive cases were only 12 months after the 2nd dose inoculation. Future studies are needed to understand if IGRA-SARS-CoV-2 can be a powerful diagnostic tool to predict future COVID-19 severe disease, guiding vaccination policies.


Assuntos
Anticorpos Antivirais , Vacina BNT162 , COVID-19 , Pessoal de Saúde , Testes de Liberação de Interferon-gama , SARS-CoV-2 , Humanos , Vacina BNT162/imunologia , COVID-19/imunologia , COVID-19/prevenção & controle , Feminino , Masculino , SARS-CoV-2/imunologia , Adulto , Pessoa de Meia-Idade , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Interferon gama/sangue , Vacinação , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , Imunidade Celular , Interleucina-10/sangue , Interleucina-10/imunologia , Interleucina-6/sangue , Interleucina-6/imunologia , Fator de Necrose Tumoral alfa/sangue
3.
Health Aff (Millwood) ; 43(5): 659-665, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38709973

RESUMO

We investigated county-level variation in mRNA COVID-19 vaccine use among Medicare beneficiaries throughout the United States. There was greater use of Pfizer-BioNTech vaccines than Moderna vaccines in urban areas for first and booster doses.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Medicare , População Rural , População Urbana , Humanos , Estados Unidos , COVID-19/prevenção & controle , População Urbana/estatística & dados numéricos , Medicare/estatística & dados numéricos , Idoso , Feminino , Masculino , Vacina BNT162 , SARS-CoV-2
4.
PLoS One ; 19(5): e0302579, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38722969

RESUMO

Since March 2020, the COVID-19 pandemic has swiftly propagated, triggering a competitive race among medical firms to forge vaccines that thwart the infection. Lebanon initiated its vaccination campaign on February 14, 2021. Despite numerous studies conducted to elucidate the characteristics of immune responses elicited by vaccination, the topic remains unclear. Here, we aimed to track the progression of anti-spike SARS-CoV-2 antibody titers at two-time points (T1: shortly after the second vaccination dose, T2: six months later) within a cohort of 201 adults who received Pfizer-BioNTech (BNT162b2), AstraZeneca, or Sputnik V vaccines in North Lebanon. Blood specimens were obtained from participants, and antibody titers against SARS-CoV-2 were quantified through the Elecsys-Anti-SARS-CoV-2 S assay (Roche Diagnostics, Switzerland). We used univariate analysis and multivariable logistic regression models to predict determinants influencing the decline in immune response and the occurrence of breakthrough infections among vaccinated patients. Among the 201 participants, 141 exhibited unchanging levels of antibody titers between the two sample collections, 55 displayed waning antibody titers, and only five participants demonstrated heightened antibody levels. Notably, age emerged as the sole variable significantly linked to the waning immune response. Moreover, the BNT162b2 vaccine exhibited significantly higher efficacy concerning the occurrence of breakthrough infections when compared with the AstraZeneca vaccine. Overall, our study reflected the immune status of a sample of vaccinated adults in North Lebanon. Further studies on a larger scale are needed at the national level to follow the immune response after vaccination, especially after the addition of the third vaccination dose.


Assuntos
Anticorpos Antivirais , COVID-19 , SARS-CoV-2 , Humanos , Masculino , Líbano/epidemiologia , Feminino , Adulto , COVID-19/prevenção & controle , COVID-19/imunologia , COVID-19/epidemiologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , SARS-CoV-2/imunologia , Pessoa de Meia-Idade , Glicoproteína da Espícula de Coronavírus/imunologia , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , Vacinação , Idoso , Adulto Jovem , Vacina BNT162/imunologia , Infecções Irruptivas
5.
Front Immunol ; 15: 1392477, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38774878

RESUMO

Introduction: Accumulating evidence indicates the importance of T cell immunity in vaccination-induced protection against severe COVID-19 disease, especially against SARS-CoV-2 Variants-of-Concern (VOCs) that more readily escape from recognition by neutralizing antibodies. However, there is limited knowledge on the T cell responses across different age groups and the impact of CMV status after primary and booster vaccination with different vaccine combinations. Moreover, it remains unclear whether age has an effect on the ability of T cells to cross-react against VOCs. Methods: Therefore, we interrogated the Spike-specific T cell responses in healthy adults of the Dutch population across different ages, whom received different vaccine types for the primary series and/or booster vaccination, using IFNÉ£ ELISpot. Cells were stimulated with overlapping peptide pools of the ancestral Spike protein and different VOCs. Results: Robust Spike-specific T cell responses were detected in the vast majority of participants upon the primary vaccination series, regardless of the vaccine type (i.e. BNT162b2, mRNA-1273, ChAdOx1 nCoV-19, or Ad26.COV2.S). Clearly, in the 70+ age group, responses were overall lower and showed more variation compared to younger age groups. Only in CMV-seropositive older adults (>70y) there was a significant inverse relation of age with T cell responses. Although T cell responses increased in all age groups after booster vaccination, Spike-specific T cell frequencies remained lower in the 70+ age group. Regardless of age or CMV status, primary mRNA-1273 vaccination followed by BNT162b2 booster vaccination showed limited booster effect compared to the BNT162b2/BNT162b2 or BNT162b2/mRNA-1273 primary-booster regimen. A modest reduction in cross-reactivity to the Alpha, Delta and Omicron BA.1, but not the Beta or Gamma variant, was observed after primary vaccination. Discussion: Together, this study shows that age, CMV status, but also the primary-booster vaccination regimen influence the height of the vaccination-induced Spike-specific T cell response, but did not impact the VOC cross-reactivity.


Assuntos
COVID-19 , Reações Cruzadas , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Linfócitos T , Humanos , Reações Cruzadas/imunologia , SARS-CoV-2/imunologia , Pessoa de Meia-Idade , Adulto , COVID-19/imunologia , COVID-19/prevenção & controle , COVID-19/virologia , Idoso , Masculino , Linfócitos T/imunologia , Feminino , Glicoproteína da Espícula de Coronavírus/imunologia , Fatores Etários , Adulto Jovem , Vacinas contra COVID-19/imunologia , Infecções por Citomegalovirus/imunologia , Infecções por Citomegalovirus/prevenção & controle , Imunização Secundária , Citomegalovirus/imunologia , Vacina BNT162/imunologia , Vacinação , Vacina de mRNA-1273 contra 2019-nCoV/imunologia , ChAdOx1 nCoV-19/imunologia , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/sangue , Idoso de 80 Anos ou mais
7.
Bratisl Lek Listy ; 125(6): 376-381, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38757595

RESUMO

AIM: The aim was to compare SARS-CoV-2 IgG antibody levels in chronic hepatitis B patients and healthcare personnel selected as the control group and to determine factors such as age, gender, vaccine type, and number of vaccines that may affect the antibody levels. MATERIALS AND METHODS: 87 chronic hepatitis B (CHB) patients followed in Ankara Training and Research Hospital Infectious Diseases Clinic and Mamak State Hospital Infectious Diseases outpatient clinic and 89 healthcare personnel selected as the control group were included in the study.SARS-CoV-2 IgG antibody levels in the serum samples of patients and healthcare personnel who received the COVID-19 vaccine were studied with the ELISA method in the Microbiology Laboratory of Ankara Training and Research Hospital, using a commercial ELISA kit (Abbott, USA) in line with the recommendations of the manufacturer. In the study, SARS-CoV-2 IgG levels were compared in CHB patients and healthcare personnel. In addition, the relationship between SARS-CoV-2 antibody level, gender, average age, natural history of the disease, number of vaccinations, vaccine type (Coronavac TM vaccine alone, BNT162b2 vaccine alone or Coronavac TM and BNT162b2 vaccine (heterologous vaccination)), treatment duration of CHB was investigated. Statistical analyses were made in the SPSS program. A value of p≤ 0.05 was considered statistically significant. FINDINGS: A total of 167 people, including 87 CKD patients and 80 healthcare personnel as the control group, were included in the study. SARS-CoV-2 IgG antibody levels were detected above the cut-off level in the entire study group, regardless of the vaccine type. No difference was detected in SARS-CoV-2 IgG titers after COVID-19 vaccination between CHB patients and healthcare personnel. There was a statistically significant difference in SARS-CoV-2 IgG antibody levels among individuals participating in the study according to vaccine types. Compared to those who received Coronavac TM vaccine alone, the average SARS-CoV-2 IgG level was found to be statistically significantly higher in those who received BNT162b2 vaccine alone or heterologous vaccination with Coronavac TM + BNT162b2 vaccine. There was no difference between the groups in terms of age, gender, number of vaccinations, natural transmission of the disease, and duration of antiviral therapy in the CHD patient group. CONCLUSION: As a result, SARS-CoV-2 IgG antibody levels above the cut-off value were achieved with Coronavac TM and BNT162b2 vaccines in both CHD patients and healthy control groups. however, both CHD patients and healthcare personnel had higher antibody levels than those who received BNT162b2 alone or those who received heterologous vaccination had higher antibody levels than those with Coronavac TM alone. Therefore, if there are no contraindications, BNT162b2 vaccine may be preferred in CHB and health personnel (Tab. 2, Ref. 14).


Assuntos
Anticorpos Antivirais , Vacina BNT162 , Vacinas contra COVID-19 , COVID-19 , Hepatite B Crônica , Imunoglobulina G , SARS-CoV-2 , Humanos , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Vacinas contra COVID-19/imunologia , COVID-19/prevenção & controle , COVID-19/imunologia , COVID-19/sangue , Imunoglobulina G/sangue , Anticorpos Antivirais/sangue , SARS-CoV-2/imunologia , Hepatite B Crônica/imunologia , Hepatite B Crônica/sangue , Vacina BNT162/imunologia , Pessoal de Saúde , Idoso , Adulto Jovem
8.
J Investig Med High Impact Case Rep ; 12: 23247096241231645, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38761096

RESUMO

Pfizer/BioNTech (BNT162b2) is a messenger RNA (mRNA) vaccine that is highly effective in preventing the most severe outcomes of COVID-19 infection. Nucleoside-modified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccines induce effective stimulation of T follicular helper (TFH) cells, leading to a robust germinal center B cell response. Side effects from the BNT162b2 vaccination, including significant lymphadenopathy, have been reported previously. Here, we present a case of angioimmunoblastic lymphoma (AITL), a rare, peripheral T-cell lymphoma with RHOA-G17v-mutated gene developing in a patient following BNT162B2 vaccine with a plausible explanation. A 60-year-old Asian female received her first dose of Pfizer BNT162B2 mRNA vaccine in August 2021. Right after her vaccination, she developed right axillary lymphadenopathy. She received her second vaccine dose in September 2021. Thereafter, she developed lymph node (LN) enlargement in her neck and groin. She underwent left posterior cervical and left groin LN excisional biopsy in April 2022 due to persistent palpable lymphadenopathy. Biopsy results then demonstrated benign follicular hyperplasia. For progressive B symptoms, a right axillary LN biopsy was done, which demonstrated AITL, with molecular studies revealing mutation in TET-2, IDH-2, and RHOA-G17v genes. Progression of AITL following BNT162B2 mRNA vaccine is limited in literature. Our case demonstrates a plausible correlation between the diagnosis of AITL following mRNA vaccination due to the malignant transformation of the TFH cells in patients who have a predisposing mutation of RHOA-17v. Given the rarity of AITL and the heterogeneity of molecular findings, more studies are needed to establish such an association.


Assuntos
Vacina BNT162 , Humanos , Feminino , Vacina BNT162/efeitos adversos , Pessoa de Meia-Idade , Proteína rhoA de Ligação ao GTP/genética , Linfadenopatia Imunoblástica , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Linfoma de Células T Periférico , SARS-CoV-2
9.
Influenza Other Respir Viruses ; 18(5): e13290, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38706402

RESUMO

BACKGROUND: Priming with ChAdOx1 followed by heterologous boosting is considered in several countries. Nevertheless, analyses comparing the immunogenicity of heterologous booster to homologous primary vaccination regimens and natural infection are lacking. In this study, we aimed to conduct a comparative assessment of the immunogenicity between homologous primary vaccination regimens and heterologous prime-boost vaccination using BNT162b2 or mRNA-1273. METHODS: We matched vaccinated naïve (VN) individuals (n = 673) with partial vaccination (n = 64), primary vaccination (n = 590), and primary series plus mRNA vaccine heterologous booster (n = 19) with unvaccinated naturally infected (NI) individuals with a documented primary SARS-CoV-2 infection (n = 206). We measured the levels of neutralizing total antibodies (NTAbs), total antibodies (TAbs), anti-S-RBD IgG, and anti-S1 IgA titers. RESULTS: Homologous primary vaccination with ChAdOx1 not only showed less potent NTAb, TAb, anti-S-RBD IgG, and anti-S1 IgA immune responses compared to primary BNT162b2 or mRNA-1273 vaccination regimens (p < 0.05) but also showed ~3-fold less anti-S1 IgA response compared to infection-induced immunity (p < 0.001). Nevertheless, a heterologous booster led to an increase of ~12 times in the immune response when compared to two consecutive homologous ChAdOx1 immunizations. Furthermore, correlation analyses revealed that both anti-S-RBD IgG and anti-S1 IgA significantly contributed to virus neutralization among NI individuals, particularly in symptomatic and pauci-symptomatic individuals, whereas among VN individuals, anti-S-RBD IgG was the main contributor to virus neutralization. CONCLUSION: The results emphasize the potential benefit of using heterologous mRNA boosters to increase antibody levels and neutralizing capacity particularly in patients who received primary vaccination with ChAdOx1.


Assuntos
Vacina de mRNA-1273 contra 2019-nCoV , Anticorpos Neutralizantes , Anticorpos Antivirais , Vacina BNT162 , Vacinas contra COVID-19 , COVID-19 , Imunização Secundária , Imunoglobulina A , Imunoglobulina G , SARS-CoV-2 , Humanos , Vacina BNT162/imunologia , Vacina BNT162/administração & dosagem , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , COVID-19/prevenção & controle , COVID-19/imunologia , Masculino , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Feminino , SARS-CoV-2/imunologia , Adulto , Vacina de mRNA-1273 contra 2019-nCoV/imunologia , Pessoa de Meia-Idade , Imunoglobulina A/sangue , Imunoglobulina A/imunologia , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , Adulto Jovem , Seguimentos , Vacinação , Idoso , Imunogenicidade da Vacina , Formação de Anticorpos/imunologia , ChAdOx1 nCoV-19/imunologia , ChAdOx1 nCoV-19/administração & dosagem , Glicoproteína da Espícula de Coronavírus/imunologia
10.
JCI Insight ; 9(9)2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38716734

RESUMO

mRNA vaccines are likely to become widely used for the prevention of infectious diseases in the future. Nevertheless, a notable gap exists in mechanistic data, particularly concerning the potential effects of sequential mRNA immunization or preexisting immunity on the early innate immune response triggered by vaccination. In this study, healthy adults, with or without documented prior SARS-CoV-2 infection, were vaccinated with the BNT162b2/Comirnaty mRNA vaccine. Prior infection conferred significantly stronger induction of proinflammatory and type I IFN-related gene signatures, serum cytokines, and monocyte expansion after the prime vaccination. The response to the second vaccination further increased the magnitude of the early innate response in both study groups. The third vaccination did not further increase vaccine-induced inflammation. In vitro stimulation of PBMCs with TLR ligands showed no difference in cytokine responses between groups, or before or after prime vaccination, indicating absence of a trained immunity effect. We observed that levels of preexisting antigen-specific CD4 T cells, antibody, and memory B cells correlated with elements of the early innate response to the first vaccination. Our data thereby indicate that preexisting memory formed by infection may augment the innate immune activation induced by mRNA vaccines.


Assuntos
Vacina BNT162 , Vacinas contra COVID-19 , COVID-19 , Citocinas , Imunidade Inata , SARS-CoV-2 , Vacinação , Humanos , Imunidade Inata/imunologia , COVID-19/imunologia , COVID-19/prevenção & controle , SARS-CoV-2/imunologia , Adulto , Masculino , Vacina BNT162/imunologia , Vacina BNT162/administração & dosagem , Feminino , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , Vacinação/métodos , Citocinas/imunologia , Vacinas de mRNA/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Pessoa de Meia-Idade , Linfócitos T CD4-Positivos/imunologia , Adulto Jovem , Vacinas Sintéticas/imunologia , Vacinas Sintéticas/administração & dosagem
11.
Curr Microbiol ; 81(7): 171, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38739274

RESUMO

A third booster doses for the 2019 coronavirus disease (COVID-19) is widely used all over the world, especially in risky individuals, with the recommendation of WHO. The purpose of this study was to evaluate the effectiveness of mRNA (BNT162b2), and CoronaVac (Sinovac Biotech) vaccines as a reminder dose following two doses of CoronaVac against COVID-19 infection, serious illness, and mortality in the geriatric population aged 75 and older during the delta variant dominant period. Our study comprised 2730 individuals the age of 75 and older in total, of which 1082 (39.6%) were male and 1648 (60.4%) were female. The vaccine effectiveness (VE) of 2 doses of CoronaVac + 1 dose of BNT162b2 vaccine combination against COVID-19 was determined as 89.2% (95% Confidence interval (CI) 80.7-93.9%), while the VE of 3 doses of CoronaVac vaccine was determined as 80.4% (95% CI 60.5-90.2%). Geriatric patients who received three doses of CoronaVac vaccine did not need intensive care. No deaths were observed in the vaccinated groups. While the VE of vaccination with 2 doses of CoronaVac + 1 dose of BNT162b2 was 41.8% (95% CI 0-74.1%) against hospitalization, 64.4% (95% CI 0-94.7%) against intensive care unit admission, the VE of vaccination with three doses of the CoronaVac was 78.2% (95% CI 0-96.5%) against hospitalization. In conclusion, our research showed that, even with the emergence of viral variants, a third dose of the CoronaVac and BNT162b2 vaccines is highly effective against symptomatic SARS-CoV-2 infection. Third-dose vaccination regimens, including heterologous and homologous vaccines, can be an effective tool in controlling the COVID-19 pandemic and the emergence of new variants.


Assuntos
Vacina BNT162 , Vacinas contra COVID-19 , COVID-19 , Imunização Secundária , SARS-CoV-2 , Eficácia de Vacinas , Humanos , Idoso , COVID-19/prevenção & controle , COVID-19/imunologia , Feminino , Masculino , Idoso de 80 Anos ou mais , SARS-CoV-2/imunologia , SARS-CoV-2/genética , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , Vacina BNT162/administração & dosagem , Vacina BNT162/imunologia , Vacinação
12.
J Med Virol ; 96(4): e29585, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38566585

RESUMO

Natural Killer (NK) cells play a significant role in the early defense against virus infections and cancer. Recent studies have demonstrated the involvement of NK cells in both the induction and effector phases of vaccine-induced immunity in various contexts. However, their role in shaping immune responses following SARS-CoV-2 vaccination remains poorly understood. To address this matter, we conducted a comprehensive analysis of NK cell phenotype and function in SARS-CoV-2 unexposed individuals who received the BNT162b2 vaccine. We employed a longitudinal study design and utilized a panel of 53 15-mer overlapping peptides covering the receptor binding domain (RBD) of the SARS-CoV-2 Spike protein to assess NK cell function at 0 and 20 days following the first vaccine, and 30 and 240 days following booster. Additionally, we evaluated the levels of total IgG anti-Spike antibodies and their potential neutralizing ability. Our findings revealed an increased NK cell activity upon re-exposure to RBD when combined with IL12 and IL18 several months after booster. Concurrently, we observed that the frequencies of NKG2A + NK cells declined over the course of the follow-up period, while NKG2C increased only in CMV positive subjects. The finding that NK cell functions are inducible 9 months after vaccination upon re-exposure to RBD and cytokines, sheds light on the role of NK cells in contributing to SARS-CoV-2 vaccine-induced immune protection and pave the way to further studies in the field.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Glicoproteína da Espícula de Coronavírus , Humanos , SARS-CoV-2 , Vacina BNT162 , Estudos Longitudinais , COVID-19/prevenção & controle , Vacinação , Células Matadoras Naturais , Anticorpos Antivirais , Anticorpos Neutralizantes
13.
Eur Rev Med Pharmacol Sci ; 28(6): 2605-2614, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38567619

RESUMO

OBJECTIVE: Both humoral and cellular immunity can be significantly influenced by the immunological responses to vaccination, and both responses are essential. Vaccination is the most consistent, safe, and cost-efficient practice for controlling the COVID-19 pandemic. PATIENTS AND METHODS: Blood samples were collected from participants who received two vaccine doses of COVID-19 Pfizer/BioNTech (BNT162b2) before and on days 7 and 10 after the first and second immunization. We evaluated some hematological and immunological markers responses to the 1st and 2nd doses of the BNT162b2 mRNA (Pfizer/BioNtech) vaccine. RESULTS: In healthy subjects' neutrophil and WBC counts significantly increased compared to those after the first dose. The results of all first-group participant categories demonstrated no discernible variations in lymphocyte counts. There was no change in IgM or IgG in all second-group cohorts, except for a considerable rise in IgG levels in people with a history of coronavirus infection following the second dosage compared to baseline. After the second dose, CD4+ T-cell and CD8+ T-cell levels rose in all groups compared to before the immunization and after the first dosage. Data demonstrated a substantial rise in neutrophil-lymphocyte ratio (NLR) after the second dose of the vaccine. Individuals who had previously had COVID-19 disease experienced a considerable increase in C3 and C4 levels after the first and second dosages compared to baseline. Additionally, compared to their levels after the first dosage, C4 levels increased significantly following the second dosage. Interleukin (IL)-6, IL-15, macrophage colony-stimulating factor (M-CSF), granulocyte colony stimulating factor (G-CSF), interferon gamma-induced protein 10 (IP-10/CXCL10), and macrophage inflammatory protein-1 alpha (MIP-1α/CCL3) levels were increased after boost correlated with Spike antibody levels, supporting their utility as indicators of successful humoral immunity development in response to vaccination. CONCLUSIONS: We can conclude that the Pfizer/BioNTech vaccine produced a more potent T-cell response than humoral ones.


Assuntos
COVID-19 , Vacinas de mRNA , Humanos , Vacina BNT162 , Pandemias , Vacinação , COVID-19/prevenção & controle , Fator Estimulador de Colônias de Granulócitos , Imunoglobulina G
14.
Eur Rev Med Pharmacol Sci ; 28(6): 2584-2592, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38567617

RESUMO

OBJECTIVE: To evaluate the vaccine effectiveness (VE) of mRNA COVID-19 vaccines in children using a meta-analysis approach. MATERIALS AND METHODS: Relevant studies on the use of mRNA COVID-19 vaccines in children were identified through computerized searches. VE-related indicators were extracted, and data analysis was performed using the R software with the meta-package. RESULTS: This study included a total of 12 relevant articles involving 9,963,732 participants from multiple centers in different countries, including the United States, Canada, Singapore, Israel, South Korea, and Qatar. The administered vaccine types included BNT162b2 and mRNA-1273. Participants were categorized into partially immunized (one dose of vaccine) and fully immunized (two doses of vaccine). Four articles reported VE after one dose of vaccine, while 12 reported VE after two doses. Heterogeneity analysis indicated significant heterogeneity among the studies, warranting the use of a random-effects model for analysis. Meta-analysis results revealed that the VE of partial immunization ranged from 16.61 (95% CI: 6.32-25.77) to 34.30 (95% CI: 24.21-43.04), with a pooled VE of 22.80 (95% CI: 15.68-29.32). The VE after full immunization ranged from 16.14 (95% CI: 14.42-17.83) to 90.47 (95% CI: 67.42-97.21), with a pooled VE of 56.17 (95% CI: 41.12-67.37). Meta-regression analysis showed no statistically significant correlation between VE and time (p>0.05). CONCLUSIONS: Both partial and full immunization of the BNT162b2 mRNA vaccine provide benefits in reducing infection rates. VE varies over time and is closely associated with viral mutations and waning immunity. The specific mechanisms require further investigation.


Assuntos
Vacina BNT162 , COVID-19 , Criança , Humanos , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Eficácia de Vacinas , RNA Mensageiro
15.
Front Immunol ; 15: 1353353, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38571939

RESUMO

As severe acute respiratory coronavirus 2 (SARS-CoV-2) variants continue to emerge, it is important to characterize immune responses against variants which can inform on protection efficacies following booster vaccination. In this study, neutralizing breadth and antigen-specific CD8+ T cell responses were analyzed in both infection-naïve and infection-experienced individuals following administration of a booster bivalent Wuhan-Hu-1+BA.4/5 Comirnaty® mRNA vaccine. Significantly higher neutralizing titers were found after this vaccination compared to the pre-third booster vaccination time point. Further, neutralizing breadth to omicron variants, including BA.1, BA.2, BA.5, BQ.1 and XBB.1, was found to be boosted following bivalent vaccination. SARS-CoV-2-specific CD8+ T cells were identified, but with no evidence that frequencies were increased following booster vaccinations. Spike protein-specific CD8+ T cells were the only responses detected after vaccination and non-spike-specific CD8+ T cells were only detected after infection. Both spike-specific and non-spike-specific CD8+ T cells were found at much lower frequencies than CD8+ T cells specific to cytomegalovirus (CMV), Epstein-Barr virus (EBV) and influenza (Flu). Taken together, these results show that the bivalent Wuhan-Hu-1+BA.4/5 Comirnaty® mRNA vaccine boosted the breadth of neutralization to newer SARS-CoV-2 variants and that vaccination is able to induce spike protein-specific CD8+ T cell responses, which are maintained longitudinally.


Assuntos
COVID-19 , Infecções por Vírus Epstein-Barr , Adulto , Humanos , Anticorpos Neutralizantes , Vacina BNT162 , Linfócitos T CD8-Positivos , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Vacinas de mRNA , COVID-19/prevenção & controle , Herpesvirus Humano 4
16.
Sci Rep ; 14(1): 8337, 2024 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-38594459

RESUMO

Accessible SARS-CoV-2-specific immunoassays may inform clinical management in people with HIV, particularly in case of persisting immunodysfunction. We prospectively studied their application in vaccine recipients with HIV, purposely including participants with a history of advanced HIV infection. Participants received one (n = 250), two (n = 249) or three (n = 42) doses of the BNT162b2 vaccine. Adverse events were documented through questionnaires. Sample collection occurred pre-vaccination and a median of 4 weeks post-second dose and 14 weeks post-third dose. Anti-spike and anti-nucleocapsid antibodies were measured with the Roche Elecsys chemiluminescence immunoassays. Neutralising activity was evaluated using the GenScript cPass surrogate virus neutralisation test, following validation against a Plaque Reduction Neutralization Test. T-cell reactivity was assessed with the Roche SARS-CoV-2 IFNγ release assay. Primary vaccination (2 doses) was well tolerated and elicited measurable anti-spike antibodies in 202/206 (98.0%) participants. Anti-spike titres varied widely, influenced by previous SARS-CoV-2 exposure, ethnicity, intravenous drug use, CD4 counts and HIV viremia as independent predictors. A third vaccine dose significantly boosted anti-spike and neutralising responses, reducing variability. Anti-spike titres > 15 U/mL correlated with neutralising activity in 136/144 paired samples (94.4%). Three participants with detectable anti-S antibodies did not develop cPass neutralising responses post-third dose, yet displayed SARS-CoV-2 specific IFNγ responses. SARS-CoV-2 vaccination is well-tolerated and immunogenic in adults with HIV, with responses improving post-third dose. Anti-spike antibodies serve as a reliable indicator of neutralising activity. Discordances between anti-spike and neutralising responses were accompanied by detectable IFN-γ responses, underlining the complexity of the immune response in this population.


Assuntos
COVID-19 , Infecções por HIV , Aranhas , Adulto , Animais , Humanos , SARS-CoV-2 , Vacina BNT162 , Vacinas contra COVID-19/efeitos adversos , COVID-19/prevenção & controle , Imunoensaio , Anticorpos , Vacinação , Anticorpos Antivirais , Anticorpos Neutralizantes
17.
Front Immunol ; 15: 1359475, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38562927

RESUMO

Background: After licensing of the protein-based vaccine NVX-CoV2373, three technically different vaccines against the SARS-CoV-2 became available for application to the human population - and for comparison of efficacies. Methods: We here recruited 42 study participants who had obtained one initial dose of NVX-CoV2373 and analyzed their immune responses in contrast to 37 study participants who had obtained either the vector vaccine AZD1222 or the mRNA vaccine BNT162b2 a year earlier. 32 participants also donated blood before first vaccination to serve as a vaccine-naive control. In detail, we investigated and quantified at day 21 and approximately six months after primary immunization the amounts of vaccine-specific antibodies produced, their neutralization capacity, their quality in terms of binding different epitopes and their efficiency in inducing various isotypes. Cellular immunity and intracellular cytokine production following in vitro re-stimulation with BNT162b2 vaccine was analyzed via ELISpot or via flow cytometry. Results: Our results show that even though vaccination including the mRNA vaccine yielded best results in almost any aspect of antibody levels and binding efficiency, the neutralization capacities against the wild-type Wuhan strain and the Omicron BA.1 variant early and at six months were comparable among all three vaccination groups. As for the T cells, we observed a prevailing CD8 response at three weeks which turned into a predominant CD4 memory at six months which has not yet been observed for AZD1222 and BNT162b2. While additional infection with SARS-CoV-2 resulted in a boost for the humoral response, T cell memory appeared rather unaffected. Conclusion: Whether any of these differences translate into real world protection from infection, mitigation of severe disease courses and prevention of long/post COVID will need to be investigated in the future.


Assuntos
Vacina BNT162 , Vacinas contra COVID-19 , Vacinas de mRNA , Humanos , ChAdOx1 nCoV-19 , Imunidade Celular , RNA Mensageiro/genética
18.
JBJS Case Connect ; 14(2)2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38608126

RESUMO

CASE: In this report, a rare case of primary cutaneous adenoid cystic carcinoma (PCACC) localized in the subcutaneous tissue of the scapular region that grew after BNT162b2 corona virus disease of 2019 (COVID-19) vaccination is presented and may be explained by CD4 and CD8 cell infiltration. The BNT162b2 mRNA vaccine has been associated with a multisystem inflammatory syndrome (MIS-V). A comparable immune reaction could potentially enhance tumor growth rate. CONCLUSION: Primary cutaneous adenoid cystic carcinomas are rare tumors with unique locations. Further studies with case series are required to establish management algorithms for PCACC and investigate the potential effect of vaccination.


Assuntos
COVID-19 , Carcinoma Adenoide Cístico , Vacinas , Humanos , Vacina BNT162 , Vacinação , Imunidade
19.
Disaster Med Public Health Prep ; 18: e66, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38618867

RESUMO

OBJECTIVE: To contain the spread of coronavirus disease 2019 (COVID-19), several vaccines have been developed. This study is intended to elucidate the level of anti-severe acute respiratory syndrome coronavirus 2 immunoglobulin G (anti-SARS-CoV-2-IgG) antibodies for COVID-19 vaccines (Pfizer BioNTech [BNT162b2], Oxford/AstraZeneca [ChAdOx1], and Sinopharm [BBIBP-CorV]) among health staff from health facilities in Duhok province, and it explored the immediate adverse reactions of COVID-19 vaccines among participants. METHODS: A longitudinal study was conducted from June 1, 2021, to June 30, 2022, and 300 participants were included through simple random sampling. RESULTS: The immune response 1 mo after the second dose was significantly higher than the sustained immune after 5 and 9 mo as results revealed that, in 100% of study samples who had (ChAdOx1) vaccine, their antibody titers exceeded the positivity threshold of 1 AU/m, while 96% for (BNT162b2) and 90% for (BBIBP-CorV) for the first test after 1 mo from the second dose of the COVID-19 vaccine, and these rates were reduced to 94.6% for (ChAdOx1), 97.8% for (BNT162b2), and 81.9% for (BBIBP-CorV) at 5 mo after the second dose, while simultaneously the seropositivity rates were more reduced at 9 mo to 46.5% for (ChAdOx1), 67.5% for (BNT162b2), and 9.20% for (BBIBP-CorV). In terms of adverse reactionsss, fever was reported as the most prevalent after the first dose in 58% for ChAdOx1, 43% for BNT162b2, and 23% for BBIBP-CorV, followed by muscle pain, joint pain, and shoulder pain for both doses. CONCLUSIONS: The implications of the findings from this study are that higher and potentially longer antibody responses can be obtained if the BNT162b2 is given as compared with the other 2 vaccines. Moreover, the booster doses of the COVID-19 vaccine are highly recommended because more than 50% of the participants either have become anti-spike protein negative or have a deficient level of anti-spike protein against COVD-19 vaccines.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Humanos , Vacinas contra COVID-19/efeitos adversos , Vacina BNT162 , SARS-CoV-2 , Estudos Longitudinais , COVID-19/epidemiologia , COVID-19/prevenção & controle , Imunoglobulina G
20.
Int J Mol Sci ; 25(7)2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38612407

RESUMO

A small fraction of people vaccinated with mRNA-lipid nanoparticle (mRNA-LNP)-based COVID-19 vaccines display acute or subacute inflammatory symptoms whose mechanism has not been clarified to date. To better understand the molecular mechanism of these adverse events (AEs), here, we analyzed in vitro the vaccine-induced induction and interrelations of the following two major inflammatory processes: complement (C) activation and release of proinflammatory cytokines. Incubation of Pfizer-BioNTech's Comirnaty and Moderna's Spikevax with 75% human serum led to significant increases in C5a, sC5b-9, and Bb but not C4d, indicating C activation mainly via the alternative pathway. Control PEGylated liposomes (Doxebo) also induced C activation, but, on a weight basis, it was ~5 times less effective than that of Comirnaty. Viral or synthetic naked mRNAs had no C-activating effects. In peripheral blood mononuclear cell (PBMC) cultures supplemented with 20% autologous serum, besides C activation, Comirnaty induced the secretion of proinflammatory cytokines in the following order: IL-1α < IFN-γ < IL-1ß < TNF-α < IL-6 < IL-8. Heat-inactivation of C in serum prevented a rise in IL-1α, IL-1ß, and TNF-α, suggesting C-dependence of these cytokines' induction, although the C5 blocker Soliris and C1 inhibitor Berinert, which effectively inhibited C activation in both systems, did not suppress the release of any cytokines. These findings suggest that the inflammatory AEs of mRNA-LNP vaccines are due, at least in part, to stimulation of both arms of the innate immune system, whereupon C activation may be causally involved in the induction of some, but not all, inflammatory cytokines. Thus, the pharmacological attenuation of inflammatory AEs may not be achieved via monotherapy with the tested C inhibitors; efficacy may require combination therapy with different C inhibitors and/or other anti-inflammatory agents.


Assuntos
COVID-19 , Inativadores do Complemento , Nanopartículas , Humanos , Lipossomos , Vacinas contra COVID-19/efeitos adversos , Leucócitos Mononucleares , Citocinas , Fator de Necrose Tumoral alfa , Vacina BNT162 , Ativação do Complemento , Lipídeos
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