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1.
Clin Immunol ; 266: 110329, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39067679

RESUMO

Overwhelming evidence has shown that aging is a significant risk factor for COVID-19-related hospitalizations, death and other adverse health outcomes. Particular T cell subsets that susceptible to aging and associated with COVID-19 disease severity requires further elucidation. Our study recruited 57 elderly patients with acute COVID-19 and 27 convalescent donors. Adaptive immunity was assessed across the COVID-19 severity spectrum. Patients underwent age-dependent CD4+ T lymphopenia, preferential loss of circulating T follicular regulatory cells (cTfh) subsets including cTfh-em, cTfh-cm, cTfh1, cTfh2, cTfh17 and circulating T follicular regulatory cells (cTfr), which regulated antibody production through different pathways and correlated with COVID-19 severity, were observed. Moreover, vaccination improved cTfh-cm, cTfh2, cTfr proportion and promoted NAb production. In conclusion, the elderly had gone through age-dependent cTfh subsets deficiency, which impeded NAb production and enabled aggravation of COVID-19 to critical illness, whereas SARS-CoV-2 vaccine inoculation helped to rejuvenate cTfh, cTfr and intensify NAb responses.


Assuntos
COVID-19 , SARS-CoV-2 , Índice de Gravidade de Doença , Células T Auxiliares Foliculares , Humanos , COVID-19/imunologia , Idoso , Masculino , Feminino , SARS-CoV-2/imunologia , Células T Auxiliares Foliculares/imunologia , Idoso de 80 Anos ou mais , Envelhecimento/imunologia , Linfócitos T Reguladores/imunologia , Pessoa de Meia-Idade , Vacinas contra COVID-19/imunologia , Fatores Etários , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Imunidade Adaptativa/imunologia
2.
J Virol ; 97(10): e0072423, 2023 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-37706688

RESUMO

IMPORTANCE: The development of broad-spectrum SARS-CoV-2 vaccines will reduce the global economic and public health stress from the COVID-19 pandemic. The use of conserved T-cell epitopes in combination with spike antigen that induce humoral and cellular immune responses simultaneously may be a promising strategy to further enhance the broad spectrum of COVID-19 vaccine candidates. Moreover, this research suggests that the combined vaccination strategies have the ability to induce both effective systemic and mucosal immunity, which may represent promising strategies for maximizing the protective efficacy of respiratory virus vaccines.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Vacinas Combinadas , Humanos , Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19/prevenção & controle , Vacinas contra COVID-19/imunologia , Imunidade Celular , Imunização , Pandemias/prevenção & controle , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Vacinação
3.
Virol Sin ; 39(4): 675-684, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38997087

RESUMO

Norovirus (NoV) infection is a major cause of gastroenteritis worldwide. The virus poses great challenges in developing vaccines with broad immune protection due to its genetic and antigenic diversity. To date, there are no approved NoV vaccines for clinical use. Here, we aimed to develop a broad-acting quadrivalent NoV vaccine based on a chimpanzee adenovirus vector, AdC68, carrying the major capsid protein (VP1) of noroviral GI and GII genotypes. Compared to intramuscular (i.m.), intranasal (i.n.), or other prime-boost immunization regimens (i.m. â€‹+ â€‹i.m., i.m. â€‹+ â€‹i.n., i.n. â€‹+ â€‹i.m.), AdC68-GI.1-GII.3 (E1)-GII.4-GII.17 (E3), administered via i.n. â€‹+ â€‹i.n. induced higher titers of serum IgG antibodies and higher IgA antibodies in bronchoalveolar lavage fluid (BALF) and saliva against the four homologous VP1s in mice. It also significantly stimulated the production of blocking antibodies against the four genotypes. In response to re-stimulation with virus-like particles (VLP)-GI.1, VLP-GII.3, VLP-GII.4, and VLP-GII.17, the quadrivalent vaccine administered according to the i.n. â€‹+ â€‹i.n. regimen effectively triggered specific cell-mediated immune responses, primarily characterized by IFN-γ secretion. Furthermore, the preparation of this novel quadrivalent NoV vaccine requires only a single recombinant adenovirus to provide broad preventive immunity against the major GI/GII epidemic strains, making it a promising vaccine candidate for further development.


Assuntos
Adenoviridae , Anticorpos Antivirais , Infecções por Caliciviridae , Vetores Genéticos , Camundongos Endogâmicos BALB C , Norovirus , Pan troglodytes , Vacinas Virais , Animais , Norovirus/imunologia , Norovirus/genética , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Camundongos , Infecções por Caliciviridae/prevenção & controle , Infecções por Caliciviridae/imunologia , Vacinas Virais/imunologia , Vacinas Virais/genética , Vacinas Virais/administração & dosagem , Vetores Genéticos/genética , Vetores Genéticos/imunologia , Adenoviridae/genética , Adenoviridae/imunologia , Feminino , Proteínas do Capsídeo/genética , Proteínas do Capsídeo/imunologia , Imunoglobulina G/sangue , Gastroenterite/prevenção & controle , Gastroenterite/virologia , Gastroenterite/imunologia , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Imunoglobulina A/sangue , Genótipo , Saliva/imunologia , Saliva/virologia , Líquido da Lavagem Broncoalveolar/imunologia , Líquido da Lavagem Broncoalveolar/virologia
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