Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 2 de 2
Filtrar
Mais filtros

Base de dados
Ano de publicação
Tipo de documento
Intervalo de ano de publicação
1.
Nat Commun ; 15(1): 8959, 2024 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-39420177

RESUMO

Development of new vaccines tailored for difficult-to-target diseases is hampered by a lack of diverse adjuvants for human use, and none of the currently available adjuvants induce Th17 cells. Here, we develop a liposomal adjuvant, CAF®10b, that incorporates Mincle and Toll-like receptor 9 agonists. In parallel mouse and non-human primate studies comparing to CAF® adjuvants already in clinical trials, we report species-specific effects of adjuvant composition on the quality and magnitude of the responses. When combined with antigen, CAF®10b induces Th1 and Th17 responses and protection against a pulmonary infection with Mycobacterium tuberculosis in mice. In non-human primates, CAF®10b induces higher Th1 responses and robust Th17 responses detectable after six months, and systemic and pulmonary Th1 and Th17 recall responses, in a sterile model of local recall. Overall, CAF®10b drives robust memory antibody, Th1 and Th17 vaccine-responses via a non-mucosal immunization route across both rodent and primate species.


Assuntos
Adjuvantes Imunológicos , Memória Imunológica , Células Th1 , Células Th17 , Receptor Toll-Like 9 , Animais , Células Th17/imunologia , Células Th17/efeitos dos fármacos , Células Th1/imunologia , Células Th1/efeitos dos fármacos , Camundongos , Adjuvantes Imunológicos/farmacologia , Adjuvantes Imunológicos/administração & dosagem , Receptor Toll-Like 9/agonistas , Receptor Toll-Like 9/imunologia , Memória Imunológica/efeitos dos fármacos , Memória Imunológica/imunologia , Feminino , Camundongos Endogâmicos C57BL , Mycobacterium tuberculosis/imunologia , Proteínas Adaptadoras de Transporte Vesicular/metabolismo , Proteínas Adaptadoras de Transporte Vesicular/imunologia , Vacinas contra a Tuberculose/imunologia , Vacinas contra a Tuberculose/administração & dosagem , Proteínas de Membrana/agonistas , Proteínas de Membrana/imunologia , Lipossomos/imunologia
2.
bioRxiv ; 2023 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-36865310

RESUMO

After clean drinking water, vaccination is the most impactful global health intervention. However, development of new vaccines against difficult-to-target diseases is hampered by the lack of diverse adjuvants for human use. Of particular interest, none of the currently available adjuvants induce Th17 cells. Here, we develop and test an improved liposomal adjuvant, termed CAF®10b, that incorporates a TLR-9 agonist. In a head-to-head study in non-human primates (NHPs), immunization with antigen adjuvanted with CAF®10b induced significantly increased antibody and cellular immune responses compared to previous CAF® adjuvants, already in clinical trials. This was not seen in the mouse model, demonstrating that adjuvant effects can be highly species specific. Importantly, intramuscular immunization of NHPs with CAF®10b induced robust Th17 responses that were observed in circulation half a year after vaccination. Furthermore, subsequent instillation of unadjuvanted antigen into the skin and lungs of these memory animals led to significant recall responses including transient local lung inflammation observed by Positron Emission Tomography-Computed Tomography (PET-CT), elevated antibody titers, and expanded systemic and local Th1 and Th17 responses, including >20% antigen-specific T cells in the bronchoalveolar lavage. Overall, CAF®10b demonstrated an adjuvant able to drive true memory antibody, Th1 and Th17 vaccine-responses across rodent and primate species, supporting its translational potential.

SELEÇÃO DE REFERÊNCIAS
Detalhe da pesquisa