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1.
Hum Vaccin Immunother ; 20(1): 2374147, 2024 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-39090779

RESUMO

Entamoeba histolytica, the causative agent of amebiasis, is one of the top three parasitic causes of mortality worldwide. However, no vaccine exists against amebiasis. Using a lead candidate vaccine containing the LecA fragment of Gal-lectin and GLA-3M-052 liposome adjuvant, we immunized rhesus macaques via intranasal or intramuscular routes. The vaccine elicited high-avidity functional humoral responses as seen by the inhibition of amebic attachment to mammalian target cells by plasma and stool antibodies. Importantly, antigen-specific IFN-γ-secreting peripheral blood mononuclear cells (PBMCs) and IgG/IgA memory B cells (BMEM) were detected in immunized animals. Furthermore, antigen-specific antibody and cellular responses were maintained for at least 8 months after the final immunization as observed by robust LecA-specific BMEM as well as IFN-γ+ PBMC responses. Overall, both intranasal and intramuscular immunizations elicited a durable and functional response in systemic and mucosal compartments, which supports advancing the LecA+GLA-3M-052 liposome vaccine candidate to clinical testing.


Assuntos
Administração Intranasal , Anticorpos Antiprotozoários , Entamoeba histolytica , Entamebíase , Interferon gama , Leucócitos Mononucleares , Lipossomos , Macaca mulatta , Vacinas Protozoárias , Animais , Entamoeba histolytica/imunologia , Lipossomos/imunologia , Lipossomos/administração & dosagem , Vacinas Protozoárias/imunologia , Vacinas Protozoárias/administração & dosagem , Anticorpos Antiprotozoários/sangue , Anticorpos Antiprotozoários/imunologia , Leucócitos Mononucleares/imunologia , Entamebíase/prevenção & controle , Entamebíase/imunologia , Interferon gama/imunologia , Interferon gama/metabolismo , Injeções Intramusculares , Imunogenicidade da Vacina , Adjuvantes de Vacinas/administração & dosagem , Adjuvantes Imunológicos/administração & dosagem , Linfócitos B/imunologia , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Imunoglobulina A/imunologia , Imunoglobulina A/sangue , Antígenos de Protozoários/imunologia , Imunidade Humoral , Memória Imunológica , Proteínas de Protozoários/imunologia
2.
Int J Pharm ; 626: 122141, 2022 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-36058408

RESUMO

Amebiasis, a disease caused by the parasite Entamoeba histolytica, is estimated to cause millions of infections and at least 55,000 deaths globally each year. With no vaccine currently available, there is an urgent need for an accessible means of stimulating protective mucosal immunity. The objective of this study was to characterize the nasal spray of a novel amebiasis vaccine candidate from a syringe-based liquid atomization device, the Teleflex MAD Nasal™, in both adult and infant nasal airways. Human ergonomic testing was completed to determine realistic actuation parameters. Spray pattern, plume geometry, and droplet size distribution were measured to evaluate reproducibility of free plume characteristics. The Alberta Idealized Nasal Inlet (AINI) and three realistic infant nasal airways were used to determine the in vitro deposition profile in adult and infant airways, respectively. Collectively, in vitro results demonstrated the feasibility of delivering the vaccine candidate to target sites within the nasal airways. Penetration through the nasal airways that could lead to deposition in the lungs was below the limit of quantification for both adult and infant geometries, indicating a low likelihood of adverse events due to lung exposure. These results support continued investigation of intranasal delivery of the synthetic Entamoeba histolytica vaccine.


Assuntos
Amebíase , Entamoeba histolytica , Adjuvantes Farmacêuticos , Adjuvantes de Vacinas , Administração Intranasal , Adulto , Aerossóis , Humanos , Lipossomos , Sprays Nasais , Reprodutibilidade dos Testes , Vacinas Sintéticas
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