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1.
Egypt J Immunol ; 31(3): 95-112, 2024 07.
Artigo em Inglês | MEDLINE | ID: mdl-38995715

RESUMO

In this study, we aimed to evaluate the immunogenic profile of a chimeric DNA-based hepatitis C virus (HCV) vaccine candidate encoding the full-length viral core-E1-E2 (HCV-CE) fragment. The vaccine candidate was designed to uniformly express the HCV genotype 4 core-E1-E2 protein. The recombinant HCV-CE protein was bacterially expressed in C41 (DE3) cells, and then BALB/c mice were immunized with different combinations of DNA/DNA or DNA/protein prime/boost immunizations. The proper construction of our vaccine candidate was confirmed by specific amplification of the encoded fragments and basic local alignment search tool (BLAST) results of the nucleotide sequence, which revealed a high degree of similarity with several HCV serotypes/genotypes. The platform for bacterial expression was optimized to maximize the yield of the purified recombinant HCV-CE protein. The recombinant protein showed high specific antigenicity against the sera of HCV-infected patients according to the ELISA and western blot results. The predicted B- and T-cell epitopes showed high antigenic and interferon-γ (IFN-γ) induction potential, in addition to cross-genotype conservation and population coverage. The mice antisera further demonstrated a remarkable ability to capture 100% of the native viral antigens circulating in the sera of HCV patients, with no cross-reactivity detected in control sera. In conclusion, the proposed HCV vaccination strategy demonstrated promising potential regarding its safety, immunogenicity, and population coverage.


Assuntos
Hepacivirus , Hepatite C , Camundongos Endogâmicos BALB C , Vacinas de DNA , Vacinas contra Hepatite Viral , Animais , Hepacivirus/imunologia , Hepacivirus/genética , Vacinas de DNA/imunologia , Vacinas de DNA/genética , Camundongos , Vacinas contra Hepatite Viral/imunologia , Hepatite C/prevenção & controle , Hepatite C/imunologia , Humanos , Imunogenicidade da Vacina/imunologia , Proteínas do Envelope Viral/imunologia , Proteínas do Envelope Viral/genética , Proteínas do Core Viral/imunologia , Proteínas do Core Viral/genética , Feminino , Anticorpos Anti-Hepatite C/imunologia , Anticorpos Anti-Hepatite C/sangue
2.
Medicina (B Aires) ; 84(3): 496-504, 2024.
Artigo em Espanhol | MEDLINE | ID: mdl-38907964

RESUMO

INTRODUCTION: The aim of this study was to evaluate the adverse effects and immune response associated with IgG anti S1 SAEA-CoV-2 antibodies among healthcare workers at Señor del Milagro Hospital in Salta city, after receiving two doses of COVID-19 vaccine. METHODS: A prospective cohort study was carried out from March 2021 to April 2022. Demographic, clinical data, adverse events supposedly attributed to vaccination (AEFIs) were collected and two samples were taken to measure serum antibody levels. RESULTS: 408 volunteers participated, 401 (98%) were vaccinated with Sputnik-V. The average age was 45.5 years with a predominance of the female sex (71%). AEFIs were reported in 188 (46.1%) and 121 (29.7%) after the first and second doses respectively (p<0.001). These events were mostly mild and transient, more frequent after the first dose. The first antibody test was positive in 99% with a mean titer of 9.7 (SD 3.7). The second dosage was positive in 88% with a mean titer of 6.4 (SD 4.4). Participants with a history of infection and previous positive testing showed significantly higher antibody titers (p<0.001). CONCLUSION: The AEFIs reported were mostly mild and transient. Mass vaccination and administration of the recommended dose are essential to achieve effective herd immunity. The majority of vaccinated healthcare workers developed antibodies and those who had the disease prior to vaccination had significant antibody titers.


Introducción: El objetivo de este estudio fue evaluar los efectos adversos y la respuesta inmune de anticuerpos IgG anti S1 SAEA-CoV-2 en el personal de Salud del Hospital del Milagro de la ciudad de Salta, posterior a recibir dos dosis de vacuna COVID-19. Métodos: Se realizó un estudio prospectivo de cohorte desde marzo de 2021 hasta abril 2022. Se recopilaron datos demográficos, clínicos, eventos adversos supuestamente atribuidos a la vacunación (ESAVI) y se tomaron dos muestras de sangre para medir los niveles de anticuerpos. Resultados: Participaron 408 voluntarios, 401 (98%) fueron vacunados con Sputnik- V. La edad promedio fue de 45.5 años con predominio del sexo femenino (71%). Los ESAVI fueron reportados en 188 (46.1%) y 121 (29.7%) luego de la primera y segunda dosis respectivamente (p<0.001). Estos eventos fueron mayormente de carácter leve y transitorios, más frecuentes luego de la primera dosis. El primer dosaje de anticuerpos fue positivo en 99% con una media de títulos de 9.7 (SD 3.7). El segundo dosaje fue positivo en 88% con una media de títulos de 6.4 (SD 4.4). Los participantes con antecedentes de infección y dosajes previos positivos mostraron títulos significativamente más altos de anticuerpos (p<0.001). Conclusión: Los ESAVI reportados fueron mayoritariamente leves y transitorios. La vacunación masiva y la administración de la dosis recomendada son esenciales para lograr una inmunidad colectiva efectiva. La mayoría de los trabajadores de la salud vacunados desarrollaron anticuerpos y aquellos que cursaron la enfermedad previa a la vacunación presentaron títulos significativos más elevados de anticuerpos.


Assuntos
Anticorpos Antivirais , Vacinas contra COVID-19 , COVID-19 , Pessoal de Saúde , SARS-CoV-2 , Humanos , Feminino , Masculino , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/efeitos adversos , Pessoal de Saúde/estatística & dados numéricos , Pessoa de Meia-Idade , Estudos Prospectivos , COVID-19/prevenção & controle , COVID-19/imunologia , Adulto , Anticorpos Antivirais/sangue , SARS-CoV-2/imunologia , Imunoglobulina G/sangue , Imunogenicidade da Vacina/imunologia
3.
Signal Transduct Target Ther ; 9(1): 129, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38740763

RESUMO

The safety and efficacy of COVID-19 vaccines in the elderly, a high-risk group for severe COVID-19 infection, have not been fully understood. To clarify these issues, this prospective study followed up 157 elderly and 73 young participants for 16 months and compared the safety, immunogenicity, and efficacy of two doses of the inactivated vaccine BBIBP-CorV followed by a booster dose of the recombinant protein vaccine ZF2001. The results showed that this vaccination protocol was safe and tolerable in the elderly. After administering two doses of the BBIBP-CorV, the positivity rates and titers of neutralizing and anti-RBD antibodies in the elderly were significantly lower than those in the young individuals. After the ZF2001 booster dose, the antibody-positive rates in the elderly were comparable to those in the young; however, the antibody titers remained lower. Gender, age, and underlying diseases were independently associated with vaccine immunogenicity in elderly individuals. The pseudovirus neutralization assay showed that, compared with those after receiving two doses of BBIBP-CorV priming, some participants obtained immunological protection against BA.5 and BF.7 after receiving the ZF2001 booster. Breakthrough infection symptoms last longer in the infected elderly and pre-infection antibody titers were negatively associated with the severity of post-infection symptoms. The antibody levels in the elderly increased significantly after breakthrough infection but were still lower than those in the young. Our data suggest that multiple booster vaccinations at short intervals to maintain high antibody levels may be an effective strategy for protecting the elderly against COVID-19.


Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , Vacinas contra COVID-19 , COVID-19 , SARS-CoV-2 , Vacinas de Produtos Inativados , Humanos , COVID-19/prevenção & controle , COVID-19/imunologia , Feminino , Masculino , Idoso , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/efeitos adversos , Vacinas contra COVID-19/administração & dosagem , SARS-CoV-2/imunologia , Estudos Prospectivos , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/sangue , Vacinas de Produtos Inativados/imunologia , Vacinas de Produtos Inativados/efeitos adversos , Vacinas de Produtos Inativados/administração & dosagem , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/sangue , Idoso de 80 Anos ou mais , Adulto , Vacinação , Estudos Longitudinais , Pessoa de Meia-Idade , Vacinas Sintéticas/imunologia , Vacinas Sintéticas/efeitos adversos , Vacinas Sintéticas/administração & dosagem , Imunogenicidade da Vacina/imunologia , Imunização Secundária
4.
Nat Med ; 30(5): 1363-1372, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38637636

RESUMO

Here we conducted a multicenter open-label, randomized phase 2 and 3 study to assess the safety and immunogenicity of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron-specific (BA.1/B.1.1.529), monovalent, thermostable, self-amplifying mRNA vaccine, GEMCOVAC-OM, when administered intradermally as a booster in healthy adults who had received two doses of BBV152 or ChAdOx1 nCoV-19. GEMCOVAC-OM was well tolerated with no related serious adverse events in both phase 2 and phase 3. In phase 2, the safety and immunogenicity of GEMCOVAC-OM was compared with our prototype mRNA vaccine GEMCOVAC-19 (D614G variant-specific) in 140 participants. At day 29 after vaccination, there was a significant rise in anti-spike (BA.1) IgG antibodies with GEMCOVAC-OM (P < 0.0001) and GEMCOVAC-19 (P < 0.0001). However, the IgG titers (primary endpoint) and seroconversion were higher with GEMCOVAC-OM (P < 0.0001). In phase 3, GEMCOVAC-OM was compared with ChAdOx1 nCoV-19 in 3,140 participants (safety cohort), which included an immunogenicity cohort of 420 participants. At day 29, neutralizing antibody titers against the BA.1 variant of SARS-CoV-2 were significantly higher than baseline in the GEMCOVAC-OM arm (P < 0.0001), but not in the ChAdOx1 nCoV-19 arm (P = 0.1490). GEMCOVAC-OM was noninferior (primary endpoint) and superior to ChAdOx1 nCoV-19 in terms of neutralizing antibody titers and seroconversion rate (lower bound 95% confidence interval of least square geometric mean ratio >1 and difference in seroconversion >0% for superiority). At day 29, anti-spike IgG antibodies and seroconversion (secondary endpoints) were significantly higher with GEMCOVAC-OM (P < 0.0001). These results demonstrate that GEMCOVAC-OM is safe and boosts immune responses against the B.1.1.529 variant. Clinical Trial Registry India identifier: CTRI/2022/10/046475 .


Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , Vacinas contra COVID-19 , COVID-19 , Imunização Secundária , SARS-CoV-2 , Humanos , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/efeitos adversos , SARS-CoV-2/imunologia , Masculino , Feminino , Adulto , COVID-19/prevenção & controle , COVID-19/imunologia , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/sangue , Pessoa de Meia-Idade , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/sangue , Imunoglobulina G/imunologia , Imunoglobulina G/sangue , Adulto Jovem , Vacinas de mRNA/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/genética , Imunogenicidade da Vacina/imunologia , ChAdOx1 nCoV-19/imunologia
5.
Clin Exp Immunol ; 217(1): 99-108, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38546123

RESUMO

Oral rotavirus vaccines demonstrate diminished immunogenicity in low-income settings where human cytomegalovirus infection is acquired early in childhood and modulates immunity. We hypothesized that human cytomegalovirus infection around the time of vaccination may influence immunogenicity. We measured plasma human cytomegalovirus-specific immunoglobulin M antibodies in rotavirus vaccinated infants from 6 weeks to 12 months old and compared rotavirus immunoglobulin A antibody titers between human cytomegalovirus seropositive and seronegative infants. There was no evidence of an association between human cytomegalovirus serostatus at 9 months and rotavirus-specific antibody titers at 12 months (geometric mean ratio 1.01, 95% CI: 0.70, 1.45; P = 0.976) or fold-increase in RV-IgA titer between 9 and 12 months (risk ratio 0.999, 95%CI: 0.66, 1.52; P = 0.995) overall. However, HIV-exposed-uninfected infants who were seropositive for human cytomegalovirus at 9 months old had a 63% reduction in rotavirus antibody geometric mean titers at 12 months compared to HIV-exposed-uninfected infants who were seronegative for human cytomegalovirus (geometric mean ratio 0.37, 95% CI: 0.17, 0.77; P = 0.008). While the broader implications of human cytomegalovirus infections on oral rotavirus vaccine response might be limited in the general infant population, the potential impact in the HIV-exposed-uninfected infants cannot be overlooked. This study highlights the complexity of immunological responses and the need for targeted interventions to ensure oral rotavirus vaccine efficacy, especially in vulnerable subpopulations.


Assuntos
Anticorpos Antivirais , Infecções por Citomegalovirus , Citomegalovirus , Infecções por HIV , Infecções por Rotavirus , Vacinas contra Rotavirus , Humanos , Vacinas contra Rotavirus/imunologia , Vacinas contra Rotavirus/administração & dosagem , Citomegalovirus/imunologia , Lactente , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Infecções por Citomegalovirus/imunologia , Infecções por Citomegalovirus/prevenção & controle , Infecções por HIV/imunologia , Masculino , Infecções por Rotavirus/imunologia , Infecções por Rotavirus/prevenção & controle , Feminino , Imunogenicidade da Vacina/imunologia , Rotavirus/imunologia , Imunoglobulina A/sangue , Imunoglobulina A/imunologia , Administração Oral , Imunoglobulina M/sangue , Imunoglobulina M/imunologia , Vacinação
6.
Pediatrics ; 153(6)2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38548700

RESUMO

BACKGROUND AND OBJECTIVES: The messenger RNA (mRNA)-based coronavirus disease 2019 vaccines approved for use in children <5 years of age have different antigen doses and administration schedules that could affect vaccine immunogenicity and effectiveness. We sought to compare the strength and breadth of serum binding and neutralizing antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) elicited by monovalent mRNA-based coronavirus disease 2019 vaccines in young children. METHODS: We conducted a prospective cohort study of children 6 months to 4 years of age who completed primary series vaccination with monovalent mRNA-1273 or BNT162b2 vaccines. Serum was collected 1 month after primary vaccine series completion for the measurement of SARS-CoV-2-specific humoral immune responses, including antibody binding responses to Spike proteins from an ancestral strain (D614G) and major variants of SARS-CoV-2 and antibody neutralizing activity against D614G and Omicron subvariants (BA.1, BA.4/5). RESULTS: Of 75 participants, 40 (53%) received mRNA-1273 and 35 (47%) received BNT162b2. Children receiving either primary vaccine series developed robust and broad SARS-CoV-2-specific binding and neutralizing antibodies, including to Omicron subvariants. Children with a previous history of SARS-CoV-2 infection developed significantly higher antibody binding responses and neutralization titers to Omicron subvariants, which is consistent with the occurrence of identified infections during the circulation of Omicron subvariants in the region. CONCLUSIONS: Monovalent mRNA-1273 and BNT162b2 elicited similar antibody responses 1 month after vaccination in young children. In addition, previous infection significantly enhanced the strength of antibody responses to Omicron subvariants. The authors of future studies should evaluate incorporation of these vaccines into the standard childhood immunization schedule.


Assuntos
Vacina de mRNA-1273 contra 2019-nCoV , Anticorpos Neutralizantes , Anticorpos Antivirais , Vacina BNT162 , COVID-19 , Imunogenicidade da Vacina , Humanos , Vacina BNT162/imunologia , Vacina BNT162/administração & dosagem , Lactente , Vacina de mRNA-1273 contra 2019-nCoV/imunologia , Pré-Escolar , Masculino , Anticorpos Neutralizantes/sangue , Estudos Prospectivos , Feminino , Imunogenicidade da Vacina/imunologia , COVID-19/prevenção & controle , COVID-19/imunologia , Anticorpos Antivirais/sangue , SARS-CoV-2/imunologia , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , Estudos de Coortes , Glicoproteína da Espícula de Coronavírus/imunologia
7.
Immunohorizons ; 7(10): 635-651, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37819998

RESUMO

Spike-encoding mRNA vaccines in early 2021 effectively reduced SARS-CoV-2-associated morbidity and mortality. New booster regimens were introduced due to successive waves of distinct viral variants. Therefore, people now have a diverse immune memory resulting from multiple SARS-CoV-2 Ag exposures, from infection to following vaccination. This level of community-wide immunity can induce immunological protection from SARS-CoV-2; however, questions about the trajectory of the adaptive immune responses and long-term immunity with respect to priming and repeated Ag exposure remain poorly explored. In this study, we examined the trajectory of adaptive immune responses following three doses of monovalent Pfizer BNT162b2 mRNA vaccination in immunologically naive and SARS-CoV-2 preimmune individuals without the occurrence of breakthrough infection. The IgG, B cell, and T cell Spike-specific responses were assessed in human blood samples collected at six time points between a moment before vaccination and up to 6 mo after the third immunization. Overall, the impact of repeated Spike exposures had a lower improvement on T cell frequency and longevity compared with IgG responses. Natural infection shaped the responses following the initial vaccination by significantly increasing neutralizing Abs and specific CD4+ T cell subsets (circulating T follicular helper, effector memory, and Th1-producing cells), but it had a small benefit at long-term immunity. At the end of the three-dose vaccination regimen, both SARS-CoV-2-naive and preimmune individuals had similar immune memory quality and quantity. This study provides insights into the durability of mRNA vaccine-induced immunological memory and the effects of preimmunity on long-term responses.


Assuntos
Vacina BNT162 , COVID-19 , Vacinas de mRNA , Humanos , Vacina BNT162/imunologia , Vacina BNT162/uso terapêutico , COVID-19/imunologia , COVID-19/prevenção & controle , Imunoglobulina G/imunologia , Vacinas de mRNA/imunologia , SARS-CoV-2 , Vacinas Sintéticas/imunologia , Imunogenicidade da Vacina/imunologia , Eficácia de Vacinas , Imunização Secundária , Subpopulações de Linfócitos/imunologia
8.
Sci Rep ; 13(1): 11798, 2023 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-37479776

RESUMO

The ChAdOx1 nCoV-19 vaccine (AZD1222) was used in Thailand during the early outbreak of coronavirus disease 2019 (COVID-19). A previous study showed a low immune response in diabetes patients after the first dose of the AZD1222 vaccine. Furthermore, humoral immune responses after the second vaccination were inconsistent. This study evaluated the immunogenicity following the first and second doses of the AZD1222 vaccine in people with type 2 diabetes (T2D) compared with the general population of Thailand. This was a prospective, single-center cohort study. 59 adults with T2D and 118 age- and sex-matched healthcare personnel were eligible. The participants received two doses of AZD1222 12 weeks apart. Antibodies against the receptor-binding domain (anti-RBD) of the SARS-CoV-2 spike protein, using an automated electrochemiluminesence immunoassay (ECLIA), were measured at baseline, 8 and 12 weeks after the first dose of vaccine, and 4 weeks after the second dose of vaccine. The anti-RBD levels were reported as the geometric mean concentration (GMC) and compared between groups using the geometric mean ratio (GMR). A total of 177 participants were included: The average age of 59 T2D patients was 60.1 years (SD: 11.4), and 31 (52.5%) of them were female. The GMC of anti-RBD 8 and 12 weeks after the first vaccination were significantly lower in T2D (week 8 60; 17.05 BAU/mL, 95% confidence interval [CI] 11.1-26.19, P = 0.035, week 12; 24.68 BAU/mL, 95% CI 16.4-37.0, P = 0.002) than in those without diabetes (week 8; 29.79 BAU/mL, 95% CI 22.07-40.42, week 12; 50.67 BAU/mL, 95% CI 40.62-63.20). However, there was no difference in the GMC of anti-RBD 4 weeks after the second vaccination among groups (T2D; 687.95 BAU/mL, 95% CI 462.7-1022.7, Normal; 697.95 BAU/mL, 95% CI 583.7-834.5, P = 0.947). In both groups, the GMC of anti-RBD was persistently high without decline 12 weeks after the first vaccination. Albuminuria was a major factor related to low humoral immune responses in T2D patients after the second dose of AZD122 vaccine (the GMR was 0.29, 95% CI 0.08-0.98, P = 0.047) whereas the HbA1C level and age were not. Immunogenicity in T2D cases was lower than in the normal population after the first dose of the AZD1222 vaccine. The two doses of AZD122 vaccine induced immunity in T2D equal to that of normal individuals in Thailand. People with diabetes should be boosted as soon as possible to induce adequate immunity to prevent COVID-19 infection.


Assuntos
COVID-19 , ChAdOx1 nCoV-19 , Diabetes Mellitus Tipo 2 , Imunogenicidade da Vacina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , ChAdOx1 nCoV-19/administração & dosagem , ChAdOx1 nCoV-19/imunologia , ChAdOx1 nCoV-19/uso terapêutico , Estudos de Coortes , COVID-19/complicações , COVID-19/imunologia , COVID-19/prevenção & controle , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/imunologia , Estudos Prospectivos , SARS-CoV-2 , População do Sudeste Asiático , Tailândia/epidemiologia , Imunogenicidade da Vacina/imunologia , Idoso
9.
Nat Commun ; 14(1): 1138, 2023 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-36878897

RESUMO

Adjuvant-containing subunit vaccines represent a promising approach for protection against tuberculosis (TB), but current candidates require refrigerated storage. Here we present results from a randomized, double-blinded Phase 1 clinical trial (NCT03722472) evaluating the safety, tolerability, and immunogenicity of a thermostable lyophilized single-vial presentation of the ID93 + GLA-SE vaccine candidate compared to the non-thermostable two-vial vaccine presentation in healthy adults. Participants were monitored for primary, secondary, and exploratory endpoints following intramuscular administration of two vaccine doses 56 days apart. Primary endpoints included local and systemic reactogenicity and adverse events. Secondary endpoints included antigen-specific antibody (IgG) and cellular immune responses (cytokine-producing peripheral blood mononuclear cells and T cells). Both vaccine presentations are safe and well tolerated and elicit robust antigen-specific serum antibody and Th1-type cellular immune responses. Compared to the non-thermostable presentation, the thermostable vaccine formulation generates greater serum antibody responses (p < 0.05) and more antibody-secreting cells (p < 0.05). In this work, we show the thermostable ID93 + GLA-SE vaccine candidate is safe and immunogenic in healthy adults.


Assuntos
Imunogenicidade da Vacina , Vacinas contra a Tuberculose , Vacinas de Subunidades Antigênicas , Adulto , Humanos , Adjuvantes Imunológicos/efeitos adversos , Adjuvantes Imunológicos/farmacologia , Adjuvantes Imunológicos/uso terapêutico , Anticorpos/imunologia , Células Produtoras de Anticorpos/imunologia , Leucócitos Mononucleares/imunologia , Vacinas contra a Tuberculose/efeitos adversos , Vacinas contra a Tuberculose/imunologia , Vacinas contra a Tuberculose/farmacologia , Vacinas contra a Tuberculose/uso terapêutico , Imunogenicidade da Vacina/imunologia , Resultado do Tratamento , Voluntários Saudáveis , Temperatura , Vacinas de Subunidades Antigênicas/administração & dosagem , Vacinas de Subunidades Antigênicas/efeitos adversos , Vacinas de Subunidades Antigênicas/imunologia , Vacinas de Subunidades Antigênicas/farmacologia , Vacinas de Subunidades Antigênicas/uso terapêutico , Método Duplo-Cego
10.
J Virol Methods ; 316: 114716, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36965633

RESUMO

Cervical cancer, the second leading cause of cancer-related deaths among women, is caused by human papillomavirus (HPV), a sexually transmitted virus. Vaccination is an effective preventive measure against viral infections and subsequent development of cervical cancer. Enzyme-linked immunosorbent assay (ELISA) is commonly used to measure specific binding antibody titers and assess the immunogenicity of test vaccines in preclinical models or clinical volunteers. Two methods of deriving titers, the endpoint titer (ET) and the effective dilution producing a median maximal effective fold of dilution (ED50) with a cut-off value, are widely used. For HPV, a pseudovirion-based neutralization assay (PBNA) is used to measure functional antibody titers. The ELISA binding titers and functional PBNA titers were found to be well-correlated for all nine HPV types tested in the vaccine, consistent with previous studies on HPV 16/18. Comparing the PBNA results with the two titration methods, the ED50 method showed higher precision and a closer correlation with PBNA results, both for individual types and pooled data analysis for all nine types. When comparing the titration results of the ET method based on a cut-off value with the ED50 method using all the data points across the dilution series, the ED50 method demonstrated better precision and a stronger correlation with PBNA results.


Assuntos
Correlação de Dados , Ensaio de Imunoadsorção Enzimática , Imunogenicidade da Vacina , Testes de Neutralização , Vacinas contra Papillomavirus , Vacinas contra Papillomavirus/classificação , Vacinas contra Papillomavirus/imunologia , Ensaio de Imunoadsorção Enzimática/métodos , Testes de Neutralização/métodos , Humanos , Masculino , Feminino , Adulto Jovem , Adulto , Anticorpos Neutralizantes/imunologia , Reprodutibilidade dos Testes , Imunogenicidade da Vacina/imunologia
11.
Viruses ; 15(3)2023 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-36992507

RESUMO

Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne pathogen for which approved therapeutic drugs or vaccines are not available. We previously developed a recombinant vesicular stomatitis virus-based vaccine candidate (rVSV-SFTSV) by replacing the original glycoprotein with Gn/Gc from SFTSV, which conferred complete protection in a mouse model. Here, we found that two spontaneous mutations, M749T/C617R, emerged in the Gc glycoprotein during passaging that could significantly increase the titer of rVSV-SFTSV. M749T/C617R enhanced the genetic stability of rVSV-SFTSV, and no further mutations appeared after 10 passages. Using immunofluorescence analysis, we found that M749T/C617R could increase glycoprotein traffic to the plasma membrane, thus facilitating virus assembly. Remarkably, the broad-spectrum immunogenicity of rVSV-SFTSV was not affected by the M749T/C617R mutations. Overall, M749T/C617R could enhance the further development of rVSV-SFTSV into an effective vaccine in the future.


Assuntos
Glicoproteínas , Mutação Puntual , Vesiculovirus , Proteínas do Envelope Viral , Vacinas Virais , Animais , Glicoproteínas/genética , Glicoproteínas/metabolismo , Phlebovirus/genética , Vesiculovirus/genética , Proteínas do Envelope Viral/genética , Vacinas Virais/genética , Vacinas Virais/imunologia , Imunogenicidade da Vacina/genética , Imunogenicidade da Vacina/imunologia , Vacinas Sintéticas/genética , Vacinas Sintéticas/imunologia , Células Vero , Chlorocebus aethiops
12.
Viruses ; 15(2)2023 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-36851527

RESUMO

Virus-like particles (VLPs), composed of the small hepatitis B virus surface antigen (HBsAgS), are the antigenic components of the hepatitis B virus (HBV) vaccine and represent the backbones for a chimeric anti-malaria vaccine and various vaccine candidates. Biological vectors have to face pre-existing anti-vector immune responses due to previous immune exposure. Vector recognition after natural infections or vaccinations can result in unwarranted outcomes, with compromising effects on clinical outcomes. In order to evaluate the impact of a pre-existing anti-HBsAgS immune response, we developed mutant VLPs composed of subunits with reduced HBsAgS-specific antigenicity. The insertion of a Plasmodium falciparum circumsporozoite protein (CSP)-derived epitope as a read-out allowed the assessment of wild type (wt) and mutant VLPs in the context of a pre-existing immune response. Mutant and wt VLP platforms with a CSP-epitope insert are immunogenic and have the ability to generate anti-CSP antibody responses in both naïve BALB/c mice and mice with a pre-existing anti-HBsAgS immune response, but with superior anti-CSP responses in mice with a pre-existing immunity. The data indicate that previous HBsAgS exposure facilitates enhanced antibody responses against foreign epitopes delivered by the HBsAgS platform, and, in this context, the state of immune sensitization alters the outcome of subsequent vaccinations.


Assuntos
Antígenos de Superfície da Hepatite B , Imunogenicidade da Vacina , Vacinas Antimaláricas , Plasmodium falciparum , Vacinas de Partículas Semelhantes a Vírus , Animais , Camundongos , Epitopos/genética , Epitopos/imunologia , Antígenos de Superfície da Hepatite B/genética , Antígenos de Superfície da Hepatite B/imunologia , Imunogenicidade da Vacina/genética , Imunogenicidade da Vacina/imunologia , Malária/prevenção & controle , Vacinas Antimaláricas/genética , Vacinas Antimaláricas/imunologia , Camundongos Endogâmicos BALB C , Modelos Animais , Plasmodium falciparum/genética , Plasmodium falciparum/imunologia , Vacinação , Vacinas de Partículas Semelhantes a Vírus/genética , Vacinas de Partículas Semelhantes a Vírus/imunologia
14.
N Engl J Med ; 388(7): 609-620, 2023 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-36791161

RESUMO

BACKGROUND: Respiratory syncytial virus (RSV) can cause serious lower respiratory tract disease in older adults, but no licensed RSV vaccine currently exists. An adenovirus serotype 26 RSV vector encoding a prefusion F (preF) protein (Ad26.RSV.preF) in combination with RSV preF protein was previously shown to elicit humoral and cellular immunogenicity. METHODS: We conducted a randomized, double-blind, placebo-controlled, phase 2b, proof-of-concept trial to evaluate the efficacy, immunogenicity, and safety of an Ad26.RSV.preF-RSV preF protein vaccine. Adults who were 65 years of age or older were randomly assigned in a 1:1 ratio to receive vaccine or placebo. The primary end point was the first occurrence of RSV-mediated lower respiratory tract disease that met one of three case definitions: three or more symptoms of lower respiratory tract infection (definition 1), two or more symptoms of lower respiratory tract infection (definition 2), and either two or more symptoms of lower respiratory tract infection or one or more symptoms of lower respiratory tract infection plus at least one systemic symptom (definition 3). RESULTS: Overall, 5782 participants were enrolled and received an injection. RSV-mediated lower respiratory tract disease meeting case definitions 1, 2, and 3 occurred in 6, 10, and 13 vaccine recipients and in 30, 40, and 43 placebo recipients, respectively. Vaccine efficacy was 80.0% (94.2% confidence interval [CI], 52.2 to 92.9), 75.0% (94.2% CI, 50.1 to 88.5), and 69.8% (94.2% CI, 43.7 to 84.7) for case definitions 1, 2, and 3, respectively. After vaccination, RSV A2 neutralizing antibody titers increased by a factor of 12.1 from baseline to day 15, a finding consistent with other immunogenicity measures. Percentages of participants with solicited local and systemic adverse events were higher in the vaccine group than in the placebo group (local, 37.9% vs. 8.4%; systemic, 41.4% vs. 16.4%); most adverse events were mild to moderate in severity. The frequency of serious adverse events was similar in the vaccine group and the placebo group (4.6% and 4.7%, respectively). CONCLUSIONS: In adults 65 years of age or older, Ad26.RSV.preF-RSV preF protein vaccine was immunogenic and prevented RSV-mediated lower respiratory tract disease. (Funded by Janssen Vaccines and Prevention; CYPRESS ClinicalTrials.gov number, NCT03982199.).


Assuntos
Anticorpos Neutralizantes , Infecções por Vírus Respiratório Sincicial , Vacinas contra Vírus Sincicial Respiratório , Vírus Sincicial Respiratório Humano , Infecções Respiratórias , Idoso , Humanos , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Método Duplo-Cego , Infecções por Vírus Respiratório Sincicial/sangue , Infecções por Vírus Respiratório Sincicial/imunologia , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Vacinas contra Vírus Sincicial Respiratório/efeitos adversos , Vacinas contra Vírus Sincicial Respiratório/uso terapêutico , Vírus Sincicial Respiratório Humano/imunologia , Infecções Respiratórias/sangue , Infecções Respiratórias/imunologia , Infecções Respiratórias/prevenção & controle , Eficácia de Vacinas , Imunogenicidade da Vacina/imunologia , Resultado do Tratamento
18.
N Engl J Med ; 387(18): 1673-1687, 2022 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-36260859

RESUMO

BACKGROUND: The safety, reactogenicity, immunogenicity, and efficacy of the mRNA-1273 coronavirus disease 2019 (Covid-19) vaccine in young children are unknown. METHODS: Part 1 of this ongoing phase 2-3 trial was open label for dose selection; part 2 was an observer-blinded, placebo-controlled evaluation of the selected dose. In part 2, we randomly assigned young children (6 months to 5 years of age) in a 3:1 ratio to receive two 25-µg injections of mRNA-1273 or placebo, administered 28 days apart. The primary objectives were to evaluate the safety and reactogenicity of the vaccine and to determine whether the immune response in these children was noninferior to that in young adults (18 to 25 years of age) in a related phase 3 trial. Secondary objectives were to determine the incidences of Covid-19 and severe acute respiratory syndrome coronavirus 2 infection after administration of mRNA-1273 or placebo. RESULTS: On the basis of safety and immunogenicity results in part 1 of the trial, the 25-µg dose was evaluated in part 2. In part 2, 3040 children 2 to 5 years of age and 1762 children 6 to 23 months of age were randomly assigned to receive two 25-µg injections of mRNA-1273; 1008 children 2 to 5 years of age and 593 children 6 to 23 months of age were randomly assigned to receive placebo. The median duration of follow-up after the second injection was 71 days in the 2-to-5-year-old cohort and 68 days in the 6-to-23-month-old cohort. Adverse events were mainly low-grade and transient, and no new safety concerns were identified. At day 57, neutralizing antibody geometric mean concentrations were 1410 (95% confidence interval [CI], 1272 to 1563) among 2-to-5-year-olds and 1781 (95% CI, 1616 to 1962) among 6-to-23-month-olds, as compared with 1391 (95% CI, 1263 to 1531) among young adults, who had received 100-µg injections of mRNA-1273, findings that met the noninferiority criteria for immune responses for both age cohorts. The estimated vaccine efficacy against Covid-19 was 36.8% (95% CI, 12.5 to 54.0) among 2-to-5-year-olds and 50.6% (95% CI, 21.4 to 68.6) among 6-to-23-month-olds, at a time when B.1.1.529 (omicron) was the predominant circulating variant. CONCLUSIONS: Two 25-µg doses of the mRNA-1273 vaccine were found to be safe in children 6 months to 5 years of age and elicited immune responses that were noninferior to those in young adults. (Funded by the Biomedical Advanced Research and Development Authority and National Institute of Allergy and Infectious Diseases; KidCOVE ClinicalTrials.gov number, NCT04796896.).


Assuntos
Vacina de mRNA-1273 contra 2019-nCoV , COVID-19 , Imunogenicidade da Vacina , Criança , Pré-Escolar , Humanos , Lactente , Adulto Jovem , Vacina de mRNA-1273 contra 2019-nCoV/imunologia , Vacina de mRNA-1273 contra 2019-nCoV/uso terapêutico , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , COVID-19/epidemiologia , COVID-19/imunologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Método Duplo-Cego , Imunogenicidade da Vacina/imunologia , Eficácia de Vacinas , Resultado do Tratamento , Adolescente , Adulto
19.
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
20.
Front Immunol ; 13: 832924, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35935974

RESUMO

Vaccination against COVID-19 in patients with end-stage renal disease (ESRD) on replacement therapy and kidney transplant recipients (KTRs) is particularly important due to the high mortality rate. Here, we tested the local and systemic immunity to the novel Pfizer BioNTech (BNT162b2) messenger RNA (mRNA) in ESRD, KTR patients, and healthy individuals (150 subjects). The ESRD group was divided into: hemodialysis (HD) and peritoneal dialysis (PD). We investigated the local and systemic immunity based on anti-N (nucleoprotein) and anti-S (spike1/2) Immunoglobulin A (IgA) and Immunoglobulin G (IgG) antibodies, respectively. Additionally, we performed an Interferon gamma (IFN-γ) release test Interferon-gamma release assay (IGRA) to monitor the cellular component of vaccine response. The control group had the highest level of anti-S IgG antibodies (153/2,080 binding antibody units (BAU)/ml) among all analyzed patients after the 1st and 2nd dose, respectively. The HD group (48/926 BAU/ml) had a diminished antibody level compared to PD (93/1,607 BAU/ml). Moreover, the seroconversion rate after the 1st dose was lower in HD than PD (56% vs. 86%). KTRs had extremely low seroconversion (33%). IgA-mediated immunity was the most effective in the control group, while other patients had diminished IgA production. We observed a lower percentage of vaccine responders based on the IFN-γ level in all research participants (100% vs. 85% in control, 100% vs. 80% in PD, 97% vs. 64% in HD). 63% of seropositive KTRs had a positive IGRA, while 28% of seronegative patients produced IFN-γ. Collectively, PD patients had the strongest response among ESRD patients. Two doses of the Pfizer vaccine are ineffective, especially in HD and KTRs. A closer investigation of ESRD and KTRs is required to set the COVID-19 vaccine clinical guidance. Clinical Trial Registration Number: www.ClinicalTrials.gov, identifier: NCT04 905 862.


Assuntos
Vacina BNT162 , COVID-19 , Imunogenicidade da Vacina , Falência Renal Crônica , Transplante de Rim , Diálise Peritoneal , Vacina BNT162/administração & dosagem , Vacina BNT162/efeitos adversos , Vacina BNT162/imunologia , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Humanos , Imunogenicidade da Vacina/imunologia , Imunoglobulina A , Imunoglobulina G , Falência Renal Crônica/terapia , Diálise Peritoneal/efeitos adversos , Diálise Renal , SARS-CoV-2
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