Leptospira immunoglobulin-like protein A variable region (LigAvar) incorporated in liposomes and PLGA microspheres produces a robust immune response correlating to protective immunity

Faisal, Syed M.; Yan, Weiwei; McDonough, Sean P.; Chang, Yung-Fu

doi:10.1016/j.vaccine.2008.10.089

Cited by 70 publications

(77 citation statements)

References 51 publications

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“…2D, IFN-γ responses from PLGA particle-vaccinated mice were higher than the liposome group. This is consistent with previous work, which showed enhanced splenocyte proliferation after a single dose of PLGA microspheres compared to multiple dose administration with similar liposomes at 6 and 14 weeks post-immunization [21]. …”

Section: Resultssupporting

confidence: 93%

Role of sustained antigen release from nanoparticle vaccines in shaping the T cell memory phenotype

Demento¹,

Cui²,

Criscione³

et al. 2012

Biomaterials

271

213

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Particulate vaccines are emerging promising technologies for the creation of tunable prophylactics against a wide variety of conditions. Vesicular and solid biodegradable polymer platforms, exemplified by liposomes and polyesters, respectively, are two of the most ubiquitous platforms in vaccine delivery studies. Here we directly compared the efficacy of each in a long-term immunization study and in protection against a model bacterial antigen. Immunization with poly(lactide-co-glycolide) (PLGA) nanoparticles elicited prolonged antibody titers compared to liposomes and alum. The magnitude of the cellular immune response was also highest in mice vaccinated with PLGA, which also showed a higher frequency of effector-like memory T cell phenotype, leading to an effective clearance of intracellular bacteria. The difference in performance of these two common particulate platforms is shown not to be due to material differences but appears to be connected to the kinetics of antigen delivery. Thus, this study highlights the importance of sustained antigen release mediated by particulate platforms and its role in the long-term appearance of effector memory cellular response.

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Section: Resultssupporting

confidence: 93%

Role of sustained antigen release from nanoparticle vaccines in shaping the T cell memory phenotype

Demento¹,

Cui²,

Criscione³

et al. 2012

Biomaterials

271

213

View full text Add to dashboard Cite

show abstract

“…Thus, these particles may be more visible to the immune system and be actively phagocytosed by APCs, resulting in effective presentation by MHCII molecules and activation of CD4 T cells. 16 Coincidentally, the significantly higher levels of IFN-γ and TNF-α induced by LBPL-OVA indicate polarization toward a Th1 immune response.…”

Section: Discussionmentioning

confidence: 99%

“…15 Liposomes elicit both antigen-specific humoral and cell-mediated immunity. 16 They have been used as a vaccine delivery system/adjuvant with various antigens, and these formulations have proved to be better than Freund's adjuvant or alum. 17 Owing to their unique self-closed structures, liposomes can entrap hydrophilic agents in the aqueous compartment and hydrophobic agents in the lipid bilayer.…”

Section: Introductionmentioning

confidence: 99%

Simple nanoliposomes encapsulating <em>Lycium barbarum</em> polysaccharides as adjuvants improve humoral and cellular immunity in mice

Sun

Zhou³

et al. 2017

IJN

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The success of subunit vaccines has been hampered by the problems of weak or short-term immunity and the lack of availability of nontoxic, potent adjuvants. It would be desirable to develop safe and efficient adjuvants with the aim of improving the cellular immune response against the target antigen. In this study, the targeting and sustained release of simple nanoliposomes containing Lycium barbarum polysaccharides (LBP) as an efficacious immune adjuvant to improve immune responses were explored. LBP liposome (LBPL) with high entrapment efficiency (86%) were obtained using a reverse-phase evaporation method and then used to encapsulate the model antigen, ovalbumin (OVA). We demonstrated that the as-synthesized liposome loaded with OVA and LBP (LBPL-OVA) was stable for 45 days and determined the encapsulation stability of OVA at 4°C and 37°C and the release profile of OVA from LBPL-OVA was investigated in pH 7.4 and pH 5.0. Further in vivo investigation showed that the antigen-specific humoral response was correlated with antigen delivery to the draining lymph nodes. The LBPL-OVA were also associated with high levels of uptake by key dendritic cells in the draining lymph nodes and they efficiently stimulated CD4 + and CD8 + T cell proliferation in vivo, further promoting antibody production. These features together elicited a significant humoral and celluar immune response, which was superior to that produced by free antigen alone.

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“…The ability to adhere to host cells and to the extracellular matrix as well as the capacity to escape complement are 2 fundamental activities that greatly contribute to successful colonization of the host. Interestingly, Lig proteins have been shown to be the most promising vaccine candidates against leptospirosis, conferring protective immunity against lethal infection in the hamster model of the disease [47][48][49][50]. One possible explanation for the usefulness of Lig proteins as vaccine antigens is that Lig-specific antibodies might be able to block binding of complement regulators and extracellular matrix molecules to the bacterial surface, thereby enhancing leptospiral susceptibility to complement-mediated killing.…”

Section: Discussionmentioning

confidence: 99%

Interação de proteínas de membrana de Leptospira com os reguladores Fator H e C4BP do sistema complemento humano.

Valencia¹

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AGRADECIMENTOSÀ minha amada família, meus pais Martha e Luis, meus irmãos Diana e Cristhian.Obrigada pelo amor incondicional, pelo apoio, pela compreensão dedicação, por entenderam minha ausência durante estes anos e principalmente por me incentivarem sempre a correr atrás dos meus sonhos com esforço e determinação.À meu namorado e amigo Darwin; por me incentivar a seguir enfrente com decisão e coragem, pela paciência, pelos conselhos e por me fazer acreditar que eu conseguiria chegar ao final desta difícil, porém gratificante etapa.À minha orientadora Dra. Lourdes Isaac por ter me recebido no seu laboratório, por ter me dado a oportunidade de construir um sonho e de conhecer o encantador mundo da Imunologia. Muito obrigada, pelo carinho, pela dedicação, pela paciência, pelos conselhos, por se alegrar com minhas conquistas, por me mostrar o caminho da ciência e por incentivar meu pensamento critico.À minha co-orientadora Dra. Angela Barbosa por ter me apresentado as leptospiras, pelo carinho, pela dedicação, pela paciência, porque nunca mediu esforços para me ajudar.Pelas longas conversas sobre os resultados e experimentos. À minha querida amiga Adriana (minha irmã aqui em Brasil), juntas embarcamos nesta aventura e descobrimos o fascino deste novo mundo, agradeço o carinho, a motivação, a ajuda o sorriso afetuoso e a companhia durante estes anos.À Tati pelo carinho, pela ajuda, por todos os bons momentos. Agradeço por ter encontrado em você uma grande amiga.Aos meus ex-colegas de laboratório: Lorena, Jose Antonio, Renan, Alda e Isabel, obrigada por me acolher na minha chegada ao laboratório, aprendí muito com vocês. A capacidade da Leptospira de escapar do sistema complemento é fundamental para a infecção seja bem sucedida. Esta hipótese é apoiada por resultados in vitro que demonstram que espécies saprófitas de leptospira morrem em poucos minutos na presença de soro humano normal, enquanto espécies patogênicas são capazes de sobreviver por longos períodos de tempo. Diferentes mecanismos envolvidos na evasão das leptospiras da morte mediada pelo complemento têm sido descritos, como a ligação a reguladores negativos do sistema complemento e a proteínas da cascata de coagulação, além da secreção de proteases capazes de interromper a ativação do sistema complemento. Neste estudo demonstramos que a aquisição do Fator H (FH) pela leptospira é crucial para a sobrevivência das bactérias no soro. A ligação de leptospiras a estes reguladores do complemento é mediada pelas proteínas leptospiral immunoglobulin-like (Lig) A e LigB, proteínas presentes somente em espécies patogênicas. FH se liga às proteínas Lig principalmente pelos short consensus repeat 5 e 20. Ensaios de competição sugerem que FH e C4BP interagem com sítios de ligação diferentes nas proteínas Lig. Ambas as proteínas reguladoras FH e C4BP mantêm atividade de co-fator, quando ligadas às Ligs, mediando a degradação de C3b e C4b pelo Fator I (FI). Para determinar o papel específico destas proteínas na evasão ao complemento foram utilizadas leptospiras transg...

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Leptospira immunoglobulin-like protein A variable region (LigAvar) incorporated in liposomes and PLGA microspheres produces a robust immune response correlating to protective immunity

Cited by 70 publications

References 51 publications

Role of sustained antigen release from nanoparticle vaccines in shaping the T cell memory phenotype

Role of sustained antigen release from nanoparticle vaccines in shaping the T cell memory phenotype

Simple nanoliposomes encapsulating <em>Lycium barbarum</em> polysaccharides as adjuvants improve humoral and cellular immunity in mice

Interação de proteínas de membrana de Leptospira com os reguladores Fator H e C4BP do sistema complemento humano.

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