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1.
Ther Innov Regul Sci ; 55(5): 1014-1018, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33939173

RESUMO

The authors aim to familiarize the reader with the Center for the State Control of Medicines, Medical Equipment and Devices (CECMED) and the agency's perspective regarding the development and implementation of regulatory sciences as an interactive tool to promote cooperation and scientific thinking. The authors share their viewpoint on the preparedness of Latin American regulatory agencies by assessing innovation (i.e. novel biopharmaceuticals, vaccines, etc.), analyzing the challenges which are impacting healthcare and patients, and posing suggestions for a collaborative regional and international approach. To conclude, the authors' share recommendations for the implementation of regional initiatives aimed at supporting regulatory science, with the goal to promote the exchange of scientific cooperation as a vital element to maximize regulatory skills and competencies.


Assuntos
COVID-19 , Vacinas , Órgãos Governamentais , Humanos , SARS-CoV-2
2.
Ther Innov Regul Sci ; 55(1): 163-169, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32720296

RESUMO

Regulatory agencies across the Latin American region have strengthened their activities through the development of new regulatory science-based tools, standards and other approaches to evaluate and assess the safety, efficacy, quality and performance of therapeutics and devices. These processes have been implemented to promote the development and authorization of innovative new drugs and technologies, which pose a challenge to even well-established regulatory frameworks. Furthermore, in today's environment, the regulatory framework to protect public health can create barriers to marketing entry of novel drugs and medical devices. This article describes the pioneering approach that the Cuban regulatory agency (CECMED) has developed with the aim of building a comprehensive regulatory framework geared to accelerated innovation and enable successful transition of novel products from research and development to clinical practice. The Office of Innovation recently established at CECMED is the first flagship initiative of this type in Latin America and the Caribbean region. Its goal is to serve a leading role as a driving force for national and regional biopharmaceutical innovation. Herein, we discuss the conceptualization and management of the Office from the Latin American regional and national Cuban contexts.


Assuntos
Preparações Farmacêuticas , Órgãos Governamentais , América Latina , Marketing
4.
Can J Microbiol ; 61(8): 531-8, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26140382

RESUMO

Vaccination is considered by the World Health Organization as the most cost-effective strategy for controlling infectious diseases. In spite of great successes with vaccines, many infectious diseases are still leading killers, because of the inadequate coverage of many vaccines. Several factors have been responsible: number of doses, high vaccine reactogenicity, vaccine costs, vaccination policy, among others. Contradictorily, few vaccines are of single dose and even less of mucosal administration. However, more common infections occur via mucosa, where secretory immunoglobulin A plays an essential role. As an alternative, we proposed a novel protocol of vaccination called Single Time Vaccination Strategy (SinTimVaS) by immunizing 2 priming doses at the same time: one by mucosal route and the other by parenteral route. Here, the mucosal and systemic responses induced by Finlay adjuvants (AF Proteoliposome 1 and AF Cochleate 1) implementing SinTimVaS in BALB/c mice were evaluated. One intranasal dose of AF Cochleate 1 and an intramuscular dose of AF Proteoliposome 1 adsorbed onto aluminum hydroxide, with bovine serum albumin or tetanus toxoid as model antigens, administrated at the same time, induced potent specific mucosal and systemic immune responses. Also, we demonstrated that SinTimVaS using other mucosal routes like oral and sublingual, in combination with the subcutaneous route elicits immune responses. SinTimVaS, as a new immunization strategy, could increase vaccination coverage and reduce time-cost vaccines campaigns, adding the benefits of immune response in mucosa.


Assuntos
Imunidade nas Mucosas , Vacinação/métodos , Adjuvantes Imunológicos/administração & dosagem , Administração Intranasal , Animais , Feminino , Imunoglobulina A Secretora/fisiologia , Camundongos , Camundongos Endogâmicos BALB C , Toxoide Tetânico/administração & dosagem
5.
Vaccine ; 32(51): 6971-6978, 2014 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-25454865

RESUMO

The response to infection against Salmonella involves both B and T cell mediated immunity. An effective immunization can activate an adequate immune response capable to control the primary infection and protect against a secondary infection. Mucosal vaccination, by inducing local pathogen-specific immune responses, has the potential to counter mucosally transmitted pathogens at the portal of entry, thereby increasing the efficacy of vaccines. The aim of this work was to explore the efficacy of AFCo1 or AFPL1, as mucosal adjuvants to stimulate cell immunity and memory responses against Vi polysaccharide antigen of Salmonella typhi (PsVi). Mice immunized with 3 intranasal doses exhibited high levels of PsVi-specific IgG (p<0.05), IgG2a and IgG2c subclasses. Also, an amplified recall response after a booster immunization with a plain polysaccharide vaccine was induced. Avidities index were higher in mice immunized with adjuvanted formulations at different chaotropic concentrations. Furthermore, IL-12 and IFN-γ levels in nasally vaccinated mice with both adjuvants were induced. Moreover, priming with 3 doses followed by booster immunization with VaxTyVi(®) resulted in high levels of anti-Vi specific IgG, IgG subclasses and antibody avidity. Long lived plasma cells in bone marrow, memory B cells and long-term memory T cells after booster dose were induced. The combined formulation of Vi polysaccharide with mucosal adjuvants provides an improved immunogenicity, in particular with regard to cellular responses and long lasting cells responses.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Linfócitos B/imunologia , Imunidade Celular , Memória Imunológica , Polissacarídeos Bacterianos/imunologia , Linfócitos T/imunologia , Vacinas Tíficas-Paratíficas/imunologia , Administração Intranasal , Animais , Anticorpos Antibacterianos/sangue , Afinidade de Anticorpos , Feminino , Imunização/métodos , Imunoglobulina G/sangue , Camundongos , Camundongos Endogâmicos C57BL , Polissacarídeos Bacterianos/administração & dosagem , Vacinas Tíficas-Paratíficas/administração & dosagem
6.
Vaccimonitor ; 23(1)ene.-abr. 2014.
Artigo em Espanhol | CUMED | ID: cum-58581

RESUMO

La acuicultura es una de las actividades económicas de mayor crecimiento para la producción de alimentos. Unode sus principales retos es la obtención de grandes volúmenes de producción con la mayor calidad posible. Esto conlleva a una reducción de la aplicación de antibióticos y productos quimioterapéuticos. Una de las estrategias más prometedoras es la aplicación de inmunopotenciadores, principalmente en los cultivos intensivos. El objetivode este trabajo fue revisar los principales inmunopotenciadores, así como las tendencias y retos de su uso mundial. Se resumen las particularidades moleculares y funcionales de los mismos y se hace énfasis en los más estudiados: levamisol, ß-glucanos, lipopolisacárido, vitamina C, extractos de plantas y hormonas. Todos estos compuestos de naturaleza heterogénea inciden mayoritariamente en los componentes de la inmunidad innata de los peces, fortaleciendo y potenciando la resistencia a enfermedades; adicionalmente algunos de ellostienen funciones antiestrés y favorecen su crecimiento. Se concluye que los inmunopotenciadores constituyen una estrategia viable para reducir las pérdidas por problemas sanitarios en el sector de la acuicultura; pero aún quedan por solucionar aspectos como la vía de administración y la etapa de inmunización adecuada para cadaespecie y tipo de cultivo(AU)


Aquaculture represents one of the fastest–growing animal food–producing sectors worldwide. One of the mainchallenges is to obtain high–volume production with the highest possible quality, this leads to reduce the use ofantibiotics and chemotherapeutics. A promising solution to these problems is the application of immune–potentiatiors mainly in intensive farming. This article aims to review the main immune–potentiators, as well as thetrends and challenges of global use of them. It summarizes the main molecular and functional characteristics withemphasis on those most studied such as levamisole, ß-glucans, lipopolysaccharide, vitamin C, plant extracts andhormones. All these heterogeneous compounds, mostly affect the innate immunity of fish, strengthening andenhancing disease resistance and some of them additionally have anti–stress effect and promote fish growth. Weconclude that immune–potentiators are a viable strategy to reduce losses for health problems in aquaculture field,however, aspects such as administration route and appropriate immunization phase for each species remains tobe solved(AU)


Assuntos
Aquicultura , Adjuvantes Imunológicos/uso terapêutico , Doenças dos Peixes/terapia
7.
Immunol Res ; 58(1): 75-85, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23660844

RESUMO

Outer-membrane vesicles (OMVs) have inherent adjuvant properties, and many vaccines use OMV as vaccine components. Utilizing the adjuvant properties of OMV could lead to the formulation of vaccines that are less expensive and potentially more immunogenic than covalently conjugated polysaccharide vaccines. We evaluated the adjuvant effect in Balb/c mice of combinations of OMV from Neisseria meningitidis serogroup A and W135 as compared to that of the non-covalently conjugated capsular polysaccharide A. Both antigens were adsorbed onto aluminum hydroxide. The mice were given a booster dose of plain polysaccharide A to stimulate an immunologic memory response. Subclasses determination and cytokine assays demonstrated the capacity of OMV to induce a IgG2a/IgG2b isotype profile and IFN-γ production, suggesting the induction of a Th1 pattern immune response. Lymphoproliferative responses to OMVs were high, with affinity maturation of antibodies observed. Bactericidal titers after the booster dose were also observed. Memory B cells and long-term memory T cells were also detected. The results of this study indicate that combined meningococcal serogroup A and W135 OMV can activate cell-mediated immunity and induce a long-term memory response.


Assuntos
Meningite Meningocócica/imunologia , Vacinas Meningocócicas/imunologia , Vacinas Meningocócicas/farmacologia , Neisseria meningitidis Sorogrupo A/imunologia , Neisseria meningitidis Sorogrupo W-135/imunologia , Proteínas R-SNARE/imunologia , Animais , Anticorpos Antibacterianos/sangue , Feminino , Imunidade Celular/imunologia , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Memória Imunológica/imunologia , Interferon gama/sangue , Interferon gama/imunologia , Meningite Meningocócica/prevenção & controle , Camundongos , Camundongos Endogâmicos BALB C , Polissacarídeos Bacterianos/imunologia , Organismos Livres de Patógenos Específicos
8.
Front Immunol ; 4: 407, 2013 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-24348475

RESUMO

The development of effective vaccines against neglected diseases, especially those associated with poverty and social deprivation, is urgently needed. Modern vaccine technologies and a better understanding of the immune response have provided scientists with the tools for rational and safer design of subunit vaccines. Often, however, subunit vaccines do not elicit strong immune responses, highlighting the need to incorporate better adjuvants; this step therefore becomes a key factor for vaccine development. In this review we outline some key features of modern vaccinology that are linked with the development of better adjuvants. In line with the increased desire to obtain novel adjuvants for future vaccines, the Finlay Adjuvant Platform offers a novel approach for the development of new and effective adjuvants. The Finlay Adjuvants (AFs), AFPL (proteoliposome), and AFCo (cochleate), were initially designed for parenteral and mucosal applications, and constitute potent adjuvants for the induction of Th1 responses against several antigens. This review summarizes the status of the Finlay technology in producing promising adjuvants for unsolved-vaccine diseases including mucosal approaches and therapeutic vaccines. Ideas related to adjuvant classification, adjuvant selection, and their possible influence on innate recognition via multiple toll-like receptors are also discussed.

9.
BMC Immunol ; 14 Suppl 1: S4, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23458578

RESUMO

The use of new adjuvants in vaccine formulations is a subject of current research. Only few parenteral adjuvants have been licensed. We have developed a mucosal and parenteral adjuvant known as AFCo1 (Adjuvant Finlay Cochleate 1, derived from proteoliposomes of N. meningitidis B) using a dialysis procedure to produce them on lab scale. The immunogenicity of the AFCo1 produced by dialysis has been already evaluated, but it was necessary to demonstrate the feasibility of a larger-scale manufacturing process. Therefore, we used a crossflow diafiltration system (CFS) that allows easy scale up to obtain large batches in an aseptic environment. The aim of this work was to produce AFCo1 on pilot scale, while conserving the adjuvant properties. The proteoliposomes (raw material) were resuspended in a buffer containing sodium deoxycholate and were transformed into AFCo1 under the action of a calcium forming buffer. The detergent was removed from the protein solution by diafiltration to a constant volume. In this CFS, we used a hollow fiber cartridge from Amicon (polysulfona cartridge of 10 kDa porosity, 1mm channel diameter of fiber and 0.45 m² area of filtration), allowing production of a batch of up to 20 L. AFCo1 were successfully produced by tangential filtration to pilot scale. The batch passed preliminary stability tests. Nasal immunization of BALB/c mice, induced specific saliva IgA and serum IgG. The induction of Th1 responses were demonstrated by the induction of IgG2a, IFNγ and not IL-5. The adjuvant action over Neisseria (self) antigens and with co-administered (heterologous) antigens such as ovalbumin and a synthetic peptide from haemolytic Streptococcus B was also demonstrated.


Assuntos
Adjuvantes Imunológicos , Vacinas Meningocócicas/biossíntese , Neisseria meningitidis Sorogrupo B/imunologia , Proteolipídeos/imunologia , Adjuvantes Imunológicos/administração & dosagem , Administração Intranasal , Animais , Anticorpos Antibacterianos/sangue , Anticorpos Antibacterianos/imunologia , Imunização , Imunoglobulina A/sangue , Imunoglobulina A/imunologia , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Interferon gama/biossíntese , Interleucina-5/biossíntese , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/imunologia , Projetos Piloto , Células Th1/imunologia
10.
Vaccimonitor ; 21(2)mayo- ago. 2012. graf
Artigo em Espanhol | CUMED | ID: cum-56219

RESUMO

El cocleato adyuvante Finlay (AFCo1) 1 es derivado de un proteopolisoma de Neisseria meningitidis serogrupo B. La transformación de los proteoliposomas en AFCo1 potencia la respuesta inmune de los antígenos de Neisseria cuando se administra por vía intranasal o intragástrica. Se ha demostrado, sin embargo, que la vía intranasal es más efectiva. Los objetivos de este trabajo fueron evaluar in vitro la liberación de proteínas del AFCo1 en líquido nasal o gástrico simulado, usando para ello la prueba de microdisolución y apoyar los resultados obtenidos cuando se administró AFCo1 por vía intranasal o intragástrica en ratones BALB/c. Los resultados demostraron que la dilución de AFCo1 en líquido gástrico o nasal simulado afecta la distribución de los antígenos de proteína de Neisseria , ya que estos se liberaron de las estructuras de cocleatos más rápido cuando se utilizó líquido nasal. Se concluyó que las condiciones que simulan el entorno gástrico afectan la distribución de los antígenos de proteínas de AFCo1 y este resultado puede explicar parcialmente porqué la administración intranasal es más efectiva in vivo que la inmunización intragástrica(AU)


Adjuvant Finlay Cochleate 1 (AFCo1) is a Proteoliposome-derived cochleate obtained from Neisseria meningitidisserogroup B. Transformation of proteoliposomes into AFCo1 potentiates the immune response on Neisseriaantigens when it is administered by intranasal or intragastric (i.g) routes. However, the i.n route has beendemonstrated to be more effective. The aim of this work is to evaluate in vitro the protein release from AFCo1, insimulated gastric fluid (SGF) or simulated nasal fluid (SNF) using a microdissolution test and to provide support for the results found when AFCo1 was administered by i.g or i.n routes in BALB/c mice. Results showed that dilution of AFCo1 in simulated gastric fluid affects the delivery of Neisseria protein antigens because they were released from cochleate structures faster than when simulated nasal fluid was used. In conclusion, conditions simulating gastric environment affect the delivery of protein antigens from AFCo1 and this result could partially explain whyin administration is more effective in vivo than in immunisation(AU)


Assuntos
Adjuvantes Imunológicos , Proteolipídeos , Neisseria
11.
J Drug Target ; 20(6): 502-8, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22632258

RESUMO

Vaccination remains the most cost-effective method for preventing infectious diseases. Key to vaccine design is the development of immunological memory, which is an essential property of the adaptive immune system. Bacterial polysaccharide conjugate vaccines are the gold standard currently used to confer protection of the host by inducing humoral immune responses against T-cell-independent antigens. Conjugate vaccines are effective, but we propose that local mucosal immune responses are likely to also play an important role in inducing immunity, and they have been less explored than systemic and adaptive immune responses. Adjuvants have been used to improve the immune response to vaccine antigens, however, no mucosal adjuvant has been licensed for human use. Here we describe the recent progress in the use of mucosal adjuvants to achieve significant immune responses against T-cell-independent antigens. We also introduce the idea that studying the mechanisms that induce cell sub-populations with strong immunological memory may facilitate the design of novel vaccine formulations, in particular in cases of B-cell unresponsiveness to thymus-independent stimuli.


Assuntos
Adjuvantes Imunológicos/farmacologia , Imunidade nas Mucosas/efeitos dos fármacos , Memória Imunológica/efeitos dos fármacos , Polissacarídeos Bacterianos/farmacologia , Linfócitos T/imunologia , Vacinas Conjugadas , Adjuvantes Imunológicos/administração & dosagem , Desenho de Fármacos , Humanos , Polissacarídeos Bacterianos/administração & dosagem , Linfócitos T/efeitos dos fármacos , Vacinas Conjugadas/administração & dosagem , Vacinas Conjugadas/imunologia
12.
Expert Rev Vaccines ; 10(7): 1007-9, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21806395

RESUMO

A 5-day workshop on adjuvant for vaccines was held in Trinidad, Cuba, on the 16-21 May 2010. Organized by the Latin American Association for Immunology and the Cuban Society for Immunology, the workshop attracted more than 60 scientists from different parts of the world. The meeting summarizes current knowledge regarding vaccine adjuvants, including delivery systems and parasitic vaccines. Main discussion topics were the discovery of new adjuvant formulations, action mechanisms for adjuvants, adjuvants for a different route of immunization, focused on mucosal vaccines, and nano- and micro-particles as a delivery system. This article highlights the most important issues presented.


Assuntos
Adjuvantes Imunológicos/uso terapêutico , Sistemas de Liberação de Medicamentos , Imunidade nas Mucosas/fisiologia , Vacinas/uso terapêutico , Composição de Medicamentos , Humanos , Imunização , Vacinas/imunologia
13.
Scand J Infect Dis ; 43(10): 809-13, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21671827

RESUMO

Increasing emphasis is being placed on the mucosal administration of vaccines in order to stimulate mucosal as well as systemic responses. Findings from our group suggest that proteoliposome-derived cochleate (AFCo1) acts as a potent mucosal adjuvant. As an alternative to chemical conjugation, the current study aimed to determine the benefit of using AFCo1 to improve the mucosal and systemic immune responses to capsular polysaccharide of Neisseria meningitidis serogroup C (PsC), a model of a thymus-independent (TI) antigen. Therefore, intranasal (i.n.) immunization of 3 doses 1 week apart with AFCo1 plus PsC in mice was conducted. Highly specific anti-PsC IgA responses and an anti-PsC IgG response were obtained. The subclass pattern induced against PsC was similar to that induced with the meningococcal vaccine. In summary, AFCo1 as nasal adjuvant was demonstrated to be capable of eliciting mucosal and systemic specific responses against a TI antigen.


Assuntos
Adjuvantes Imunológicos/farmacologia , Antígenos de Bactérias/imunologia , Cápsulas Bacterianas/imunologia , Vacinas Meningocócicas/farmacologia , Neisseria meningitidis Sorogrupo C/imunologia , Proteolipídeos/farmacologia , Administração Intranasal , Animais , Anticorpos Antibacterianos/análise , Anticorpos Antibacterianos/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Imunoglobulina A/análise , Imunoglobulina G/sangue , Injeções Intramusculares , Infecções Meningocócicas/imunologia , Infecções Meningocócicas/prevenção & controle , Vacinas Meningocócicas/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Neisseria meningitidis Sorogrupo C/química , Proteolipídeos/imunologia
14.
Can J Microbiol ; 57(3): 256-61, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21358768

RESUMO

Mucosal immune responses are an early and important line of defense against pathogens. The current understanding of the mucosal immune system allows us to consider the use of nasal immunization for induction of antigen-specific immune responses at the mucosal surface and the systemic compartment. Mucosal adjuvants are key for developing novel mucosal vaccines and represent 1 approach to improving mucosal and systemic immunity. However, few mucosal vaccine adjuvants are currently approved for human use. Neisseria meningitidis B proteoliposome-derived cochleate (AFCo1 - Adjuvant Finlay Cochleate 1) has been demonstrated to be a potent mucosal adjuvant. The present work demonstrates that intranasal immunization of 3 doses of tetanus toxoid (TT) coadministered with AFCo1 in mice promotes high systemic and mucosal responses. The anti-TT IgG serum titers and the mucosal anti-TT IgA in saliva and vaginal wash were significantly higher than TT alone. The analysis of antibody subclasses showed that intranasal administration of AFCo1 + TT induced not only IgG1 but also IgG2a anti-TT antibodies at levels comparable to those obtained with TT vaccine (vax-TET). These data support the fact that AFCo1 is a potent mucosal adjuvant in nasal immunization to a coadministered protein antigen.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Imunidade nas Mucosas , Imunoglobulina G/sangue , Toxoide Tetânico/imunologia , Administração Intranasal , Administração Intravaginal , Animais , Formação de Anticorpos , Feminino , Imunoglobulina A Secretora/imunologia , Imunoglobulina G/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Neisseria meningitidis Sorogrupo B , Proteolipídeos/administração & dosagem , Proteolipídeos/imunologia , Saliva/imunologia , Toxoide Tetânico/administração & dosagem , Vagina/imunologia
15.
Vaccimonitor ; 18(2)mayo-ago. 2009. ilus, graf, tab
Artigo em Inglês | CUMED | ID: cum-43098

RESUMO

Adjuvants may be classified into delivery systems and immune potentiator or modulator molecules based on their mechanism of action. Neisseria vaccines containing traditional adjuvants such as aluminium salts have existed for long time, but meningitis caused by Neisseria meningitidis serogroups, particularly serogroup B, continues to be a global health problem. Novel strategies have applied in silico and recombinant technologies to develop universal antigens (e.g. proteins, peptides and plasmid DNA) for vaccines, but these antigens have been shown to be poorly immunogenic even when alum adjuvanted, implying a need for better vaccine design. In this work we review the use of natural, detoxified, or synthetic molecules in combination with antigens to activate the innate immune system and to modulate the adaptive immune responses. In the main, antigenic and imune potentiator signals are delivered using nano-, micro-particles, alum, or emulsions. The importance of interaction between adjuvants and antigens to activate and target dendritic cells, the bridge between the innate and adaptive immune systems, will be discussed. In addition, nasal vaccine strategies based on the development of mucosal adjuvants and Neisseria derivatives to eliminate the pathogen at the site of infection provide promising adjuvants effective not only against respiratory pathogens, but also against pathogens responsible for enteric and sexually transmitted diseases(AU)


Assuntos
Vacinas Meningocócicas/imunologia
16.
Vaccimonitor ; 18(2)mayo-ago. 2009. ilus, graf, tab
Artigo em Inglês | CUMED | ID: cum-43097

RESUMO

Neonates have a poorly developed immune system. Respiratory pathogens cause disease during early periods of live. Consequently, it is important to develop protective vaccines that induce immunity and immunological memory against respiratory pathogens early in life. Intranasal (i.n.) route could be an effective via for immunization. Therefore, we explored the effectiveness of AF (Adjuvant Finlay) PL1 (Proteoliposome) from Neisseria meningitidis serogroup B and its derivate Cochleate (AFCo1) by nasal route in neonatal mice. They were immunized i,n, 3 times 7 days apart and anti PL systemic and mucosal antibody response were measured by ELISA. In addition, a prime-boost strategy was used to evaluate the humoral immune response in neonate mice. The 3 doses of AFPL1 or AFCo1 induced significant levels of anti PL IgG antibodies in comparison whit control, but AFCo1 (2017 U/mL) was significantly higher than AFPL1 (1107 U/mL). AFCo1 and AFPL1 induced a predominant Th1 pattern with IgG2a/IgG1 >1 by i,n, immunization and AFCo1 induced a high anti PL IgA saliva response in saliva. Interestingly, one nasally prime at 7 days of born and a memory one boost i,n, dose 9 weeks later with AFCo1 or AFPL1 showed similar specific IgG levels and IgG2a/IgG1 relation than 3 i.n. doses in adult mice. In conclusion, these results represent the first report of neonatal intranasal vaccination using AFCo1 capable to induce systemic and mucosal immunity and priming for memory(AU)


Assuntos
Animais , Camundongos , Vacinas Meningocócicas/imunologia , Imunidade nas Mucosas
17.
Vaccimonitor ; 18(2)mayo-ago. 2009. ilus, graf, tab
Artigo em Inglês | CUMED | ID: cum-43095

RESUMO

Mucosal vaccination offers attractive advantages to conventional systemic vaccination. Most pathogens enter or establish infection at mucosal surfaces. This represents an enormous challenge for vaccine development. Nevertheless, the availability of safe and effective adjuvants that function mucosally is the major limitation. Therefore, we investigated the impact of mucosal immunization with the Neisseria meningitidis B proteoliposome (AFPL1, Adjuvant Finlay Proteoliposome 1) and its-derived cochleate (Co, AFCo1). They contain multiple PAMPs as immunopotentiators and have delivery system ability as well as Th1 polarization activity. Groups of female mice were immunized by nasal, oral, intravaginal, or intramuscular routes with three doses with AFPL1/AFCo1 alone or containing ovalbumin or glycoprotein (g) D2 from Herpes Simplex Virus type 2 (HSV-2). High levels of specific IgG antibodies were detected in sera of mice vaccinated with either route. However, specific IgA antibodies were produced in saliva and vaginal wash only following mucosal delivering. The polarization to a Th1 pattern was confirmed by testing the induction of IgG2a/IgG2c antibody, positive delayed-type hypersensitivity reactions, and gIFN production. Additionally, AFCo1gD2 showed practically no vaginal HSV-2 replication and 100 percent protection against lethal vaginal HSV-2 challenge. In conclusion, the results support the use of AFCo1 as potent Th1 adjuvant for mucosal vaccines, particularly for nasal route(AU)


Assuntos
Vacinas Meningocócicas/imunologia
18.
Expert Rev Vaccines ; 8(8): 987-92, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19627182

RESUMO

A 5-day workshop on Neisseria vaccines was held in Varadero, Cuba, 17-22 May 2009, and hosted by the Latin American Association for Immunology and the Cuban Society for Immunology, which attracted more than 100 scientists from different parts of the world. The meeting summarizes current knowledge regarding Neisseria species vaccine development, including plain polysaccharide vaccines, conjugate polysaccharides and protein-based vaccines. Main discussion topics were the discovery of new potential antigens with protective capacity, current and new vaccines, pathogenesis and immune response, clinical trials and alternative correlates of protection and manufacture, control and regulation, gonococcus vaccines, and adjuvant as the main component of Neisseria vaccines. Seven keynote addresses, 32 oral presentations, 49 posters and an International Vaccine Course were presented. The meeting was concluded with a 'Hot Topics' session discussing future challenges. This article highlights the most important issues presented.


Assuntos
Gonorreia/prevenção & controle , Meningite Meningocócica/prevenção & controle , Vacinas Meningocócicas , Humanos , Neisseria gonorrhoeae/imunologia , Neisseria gonorrhoeae/patogenicidade , Neisseria meningitidis/imunologia , Neisseria meningitidis/patogenicidade
19.
Methods ; 49(4): 309-15, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19545630

RESUMO

Conservative estimates place the death toll from cholera at more than 100,000 persons each year. A particulate mucosal vaccine strategy combining antigens and immune stimulator molecules from Vibrio cholerae to overcome this problem is described. Proteoliposomes extracted from V. cholerae O1 were transformed into cochleates (AFCo2, Adjuvant Finlay cochleate 2) through a calcium inducible rotary dialysis method. Light microscopy was carried out and tubules of 16.25+/-4.57 microm in length were observed. Western blots were performed to verify the immunochemical properties of the main AFCo2 incorporated antigens, revealing full recognition of the outer membrane protein U (OmpU), lipopolysaccharide (LPS), and mannose-sensitive hemagglutinin (MSHA) antigens. AFCo2 were administered by the intranasal route using a two or three dose schedule and the immune response against V. cholerae antigens was assessed. Three AFCo2 doses were required to induce significant (p<0.05), antigen specific IgA in saliva (1.34+/-0.135) and feces (0.60+/-0.089). While, two or three doses of AFCo2 or proteoliposomes induce similar specific IgG and vibriocidal activity responses in sera. These results show for the first time that AFCo2 can be obtained from V. cholerae O1 proteoliposomes and have the potential to protect against the pathogen when administered intranasally.


Assuntos
Membrana Mucosa/imunologia , Proteolipídeos/administração & dosagem , Proteolipídeos/imunologia , Vibrio cholerae O1/imunologia , Administração Intranasal , Animais , Ácido Desoxicólico/administração & dosagem , Ácido Desoxicólico/imunologia , Ácido Edético/administração & dosagem , Ácido Edético/imunologia , Feminino , Imunidade nas Mucosas/efeitos dos fármacos , Imunidade nas Mucosas/imunologia , Imunoglobulina G/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Membrana Mucosa/efeitos dos fármacos
20.
Methods ; 49(4): 301-8, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19410000

RESUMO

Most pathogens either invade the body or establish infection in mucosal tissues and represent an enormous challenge for vaccine development by the absence of good mucosal adjuvants. A proteoliposome-derived adjuvant from Neisseria meningitidis serogroup B (AFPL1, Adjuvant Finlay Proteoliposome 1) and its derived cochleate form (Co, AFCo1) contain multiple pathogen-associated molecular patterns as immunopotentiators, and can also serve as delivery systems to elicit a Th1-type immune response. The present studies demonstrate the ability of AFPL1and AFCo1 to induce mucosal and systemic immune responses by different mucosal immunizations routes and significant adjuvant activity for antibody responses of both structures: a microparticle and a nanoparticle with a heterologous antigen. Therefore, we used female mice immunized by intragastric, intravaginal, intranasal or intramuscular routes with both structures alone or incorporated with ovalbumin (OVA). High levels of specific IgG antibody were detected in all sera and in vaginal washes, but specific IgA antibody in external secretions was only detected in mucosally immunized mice. Furthermore, antigen specific IgG1 and IgG2a isotypes were all induced. AFPL1 and AFCo1 are capable of inducing IFN-gamma responses, and chemokine secretions, like MIP-1alpha and MIP-1beta. However, AFCo1 is a better alternative to induce immune responses at mucosal level. Even when we use a heterologous antigen, the AFCo1 response was better than with AFPL1 in inducing mucosal and systemic immune responses. These results support the use of AFCo1 as a potent Th1 inducing adjuvant particularly suitable for mucosal immunization.


Assuntos
Imunização/métodos , Membrana Mucosa/imunologia , Neisseria meningitidis Sorogrupo B/imunologia , Proteolipídeos/administração & dosagem , Proteolipídeos/imunologia , Administração Intranasal , Administração Intravaginal , Animais , Células Cultivadas , Ácido Desoxicólico/administração & dosagem , Ácido Desoxicólico/imunologia , Ácido Edético/administração & dosagem , Ácido Edético/imunologia , Feminino , Imunidade nas Mucosas/efeitos dos fármacos , Imunidade nas Mucosas/imunologia , Imunoglobulina A/biossíntese , Imunoglobulina G/biossíntese , Camundongos , Camundongos Endogâmicos BALB C , Membrana Mucosa/efeitos dos fármacos
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