RESUMO
Salmonella enterica infections remain a challenging health issue, causing significant morbidity and mortality worldwide. Current vaccines against typhoid fever display moderate efficacy whilst no licensed vaccines are available for paratyphoid fever or invasive non-typhoidal salmonellosis. Therefore, there is an urgent need to develop high efficacy broad-spectrum vaccines that can protect against typhoidal and non-typhoidal Salmonella. The Salmonella outer membrane porins OmpC and OmpF, have been shown to be highly immunogenic antigens, efficiently eliciting protective antibody, and cellular immunity. Furthermore, enterobacterial porins, particularly the OmpC, have a high degree of homology in terms of sequence and structure, thus making them a suitable vaccine candidate. However, the degree of the amino acid conservation of OmpC among typhoidal and non-typhoidal Salmonella serovars is currently unknown. Here we used a bioinformatical analysis to classify the typhoidal and non-typhoidal Salmonella OmpC amino acid sequences into different clades independently of their serological classification. Further, our analysis determined that the porin OmpC contains various amino acid sequences that are highly conserved among both typhoidal and non-typhoidal Salmonella serovars. Critically, some of these highly conserved sequences were located in the transmembrane ß-sheet within the porin ß-barrel and have immunogenic potential for binding to MHC-II molecules, making them suitable candidates for a broad-spectrum Salmonella vaccine. Collectively, these findings suggest that these highly conserved sequences may be used for the rational design of an effective broad-spectrum vaccine against Salmonella.
Assuntos
Proteínas de Bactérias/genética , Porinas/genética , Salmonella/genética , Sequência de Aminoácidos , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Sequência Conservada , Humanos , Filogenia , Porinas/química , Porinas/metabolismo , Conformação Proteica em alfa-Hélice , Salmonella/química , Salmonella/classificação , Salmonella/metabolismo , Infecções por Salmonella/microbiologia , Salmonella typhi/química , Salmonella typhi/classificação , Salmonella typhi/genética , Salmonella typhi/metabolismo , Alinhamento de Sequência , Febre Tifoide/microbiologiaRESUMO
Several microbial components, such as bacterial DNA and flagellin, have been used as experimental vaccine adjuvants because of their inherent capacity to efficiently activate innate immune responses. Likewise, our previous work has shown that the major Salmonella Typhi (S. Typhi) outer membrane proteins OmpC and OmpF (porins) are highly immunogenic protective antigens that efficiently stimulate innate and adaptive immune responses in the absence of exogenous adjuvants. Moreover, S. Typhi porins induce the expression of costimulatory molecules on antigen-presenting cells through toll-like receptor canonical signaling pathways. However, the potential of major S. Typhi porins to be used as vaccine adjuvants remains unknown. Here, we evaluated the adjuvant properties of S. Typhi porins against a range of experimental and clinically relevant antigens. Co-immunization of S. Typhi porins with ovalbumin (OVA), an otherwise poorly immunogenic antigen, enhanced anti-OVA IgG titers, antibody class switching, and affinity maturation. This adjuvant effect was dependent on CD4+ T-cell cooperation and was associated with an increase in IFN-γ, IL-17A, and IL-2 production by OVA-specific CD4+ T cells. Furthermore, co-immunization of S. Typhi porins with an inactivated H1N1 2009 pandemic influenza virus experimental vaccine elicited higher hemagglutinating anti-influenza IgG titers, antibody class switching, and affinity maturation. Unexpectedly, co-administration of S. Typhi porins with purified, unconjugated Vi capsular polysaccharide vaccine (Vi CPS)-a T-independent antigen-induced higher IgG antibody titers and class switching. Together, our results suggest that S. Typhi porins OmpC and OmpF are versatile vaccine adjuvants, which could be used to enhance T-cell immune responses toward a Th1/Th17 profile, while improving antibody responses to otherwise poorly immunogenic T-dependent and T-independent antigens.
RESUMO
In the present work, we report, for the first time, on the purification of the Salmonella Typhimurium OmpD porin. We assessed the integrity and purity of the protein and evaluated the immunogenicity of the protein and its ability to induce antibody without exogenous adjuvant. We observed that 10 µg OmpD induced high antibody levels of IgM and IgG, which were maintained for more than 260 days after immunization. Immunization with OmpD induced multiple IgG antibody isotypes including IgG1, IgG2a, IgG2b, and IgG3 subclasses. Furthermore, these antibodies were able to recognize and bind to the bacterial surface. Our results demonstrate the high immunogenicity of S. Typhimurium OmpD porin, which induces long-lasting antibodies which may be and important target of the immune response against Salmonella infection. In conclusion, we propose the OmpD porin could be used within novel subunit vaccine formulations that do not need additional adjuvant and that confer long lasting humoral immunity against Salmonella infections.
Assuntos
Anticorpos Antibacterianos/imunologia , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Porinas/imunologia , Porinas/isolamento & purificação , Salmonella typhimurium/imunologia , Animais , Afinidade de Anticorpos , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Vacinas contra Salmonella/imunologiaRESUMO
The influenza virus is a human pathogen that causes epidemics every year, as well as potential pandemic outbreaks, as occurred in 2009. Vaccination has proven to be sufficient in the prevention and containment of viral spreading. In addition to the current egg-based vaccines, new and promising vaccine platforms, such as cell culture-derived vaccines that include virus-like particles (VLPs), have been developed. VLPs have been shown to be both safe and immunogenic against influenza infections. Although antibody persistence has been studied in traditional egg-based influenza vaccines, studies on antibody response durations induced by VLP influenza vaccines in humans are scarce. Here, we show that subjects vaccinated with an insect cell-derived VLP vaccine, in the midst of the 2009 H1N1 influenza pandemic outbreak in Mexico City, showed antibody persistence up to 24 months post-vaccination. Additionally, we found that subjects that reported being revaccinated with a subsequent inactivated influenza virus vaccine showed higher antibody titres to the pandemic influenza virus than those who were not revaccinated. These findings provide insights into the duration of the antibody responses elicited by an insect cell-derived pandemic influenza VLP vaccine and the possible effects of subsequent influenza vaccination on antibody persistence induced by this VLP vaccine in humans.
Assuntos
Anticorpos Antivirais/sangue , Vírus da Influenza A Subtipo H1N1/imunologia , Vacinas contra Influenza/imunologia , Vacinação , Vacinas de Partículas Semelhantes a Vírus/imunologia , Adulto , Idoso , Estudos Transversais , Método Duplo-Cego , Feminino , Humanos , Imunização Secundária , Influenza Humana/epidemiologia , Influenza Humana/virologia , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Pandemias , Estudos Soroepidemiológicos , Fatores de Tempo , Vacinas de Produtos Inativados , Adulto JovemRESUMO
BACKGROUND AND AIMS: Severe influenza A(H1N1)pdm2009 virus infection cases are characterized by sustained immune activation during influenza pandemics. Seasonal flu data suggest that immune mediators could be modified by wave-related changes. Our aim was to determine the behavior of soluble and cell-related mediators in two waves at the epicenter of the 2009 influenza pandemic. METHODS: Leukocyte surface activation markers were studied in serum from peripheral blood samples, collected from the 1(st) (April-May, 2009) and 2(nd) (October 2009-February 2010) pandemic waves. Patients with confirmed influenza A(H1N1)pdm2009 virus infection (H1N1), influenza-like illness (ILI) or healthy donors (H) were analyzed. RESULTS: Serum IL-6, IL-4 and IL-10 levels were elevated in H1N1 patients from the 2(nd) pandemic wave. Additionally, the frequency of helper and cytotoxic T cells was reduced during the 1(st) wave, whereas CD69 expression in helper T cells was increased in the 2(nd) wave for both H1N1 and ILI patients. In contrast, CD62L expression in granulocytes from the ILI group was increased in both waves but in monocytes only in the 2(nd) wave. Triggering Receptor Expressed on Myeloid cells (TREM)-1 expression was elevated only in H1N1 patients at the 1(st) wave. CONCLUSIONS: Our results show that during the 2009 influenza pandemic a T cell activation phenotype is observed in a wave-dependent fashion, with an expanded activation in the 2(nd) wave, compared to the 1(st) wave. Conversely, granulocyte and monocyte activation is infection-dependent. This evidence collected at the pandemic epicenter in 2009 could help us understand the differences in the underlying cellular mechanisms that drive the wave-related immune profile behaviors that occur against influenza viruses during pandemics.
Assuntos
Vírus da Influenza A Subtipo H1N1/imunologia , Influenza Humana/imunologia , Interleucina-10/sangue , Interleucina-4/sangue , Interleucina-6/sangue , Linfócitos T Citotóxicos/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Adolescente , Adulto , Idoso , Antígenos CD/biossíntese , Antígenos de Diferenciação de Linfócitos T/biossíntese , Biomarcadores , Contagem de Linfócito CD4 , Feminino , Humanos , Influenza Humana/virologia , Interleucina-10/imunologia , Interleucina-4/imunologia , Interleucina-6/imunologia , Selectina L/biossíntese , Lectinas Tipo C/biossíntese , Ativação Linfocitária/imunologia , Masculino , Glicoproteínas de Membrana/biossíntese , Pessoa de Meia-Idade , Monócitos/imunologia , Neutrófilos/imunologia , Pandemias , Receptores Imunológicos/biossíntese , Receptor Gatilho 1 Expresso em Células Mieloides , Adulto JovemRESUMO
While around 20% of the Amazonian forest has been cleared for pastures and agriculture, one fourth of the remaining forest is dedicated to wood production. Most of these production forests have been or will be selectively harvested for commercial timber, but recent studies show that even soon after logging, harvested stands retain much of their tree-biomass carbon and biodiversity. Comparing species richness of various animal taxa among logged and unlogged forests across the tropics, Burivalova et al. found that despite some variability among taxa, biodiversity loss was generally explained by logging intensity (the number of trees extracted). Here, we use a network of 79 permanent sample plots (376 ha total) located at 10 sites across the Amazon Basin to assess the main drivers of time-to-recovery of post-logging tree carbon (Table S1). Recovery time is of direct relevance to policies governing management practices (i.e., allowable volumes cut and cutting cycle lengths), and indirectly to forest-based climate change mitigation interventions.
Assuntos
Biomassa , Carbono/metabolismo , Conservação dos Recursos Naturais , Agricultura Florestal , Florestas , Bolívia , Brasil , SurinameRESUMO
INTRODUCTION: On April 2009, the Mexican Ministry of Health received notification of cases of severe pneumonia mostly affecting young healthy people; this was the beginning of the first influenza pandemic of the 21st century. The nature of the immune response to the influenza A(H1N1)2009 pandemic strain in Mexico at the beginning of the pandemic outbreak has not been completely defined. We describe the serological response to the 2009 pandemic influenza virus in paediatric patients with influenza-like illness, their household contacts (HHCs), and exposed health-care workers (HCWs) at the beginning of the pandemic outbreak in Mexico City. METHODOLOGY: thirty pre-epidemic and 129 epidemic samples were collected and serum antibodies were measured against A(H1N1)2009 pandemic virus and two non-pandemic swine influenza viruses by an haemagglutination inhibition assay . RESULTS: 91% (29/32) of the convalescence samples from confirmed patients had an antibody titre ≥ 10 (GMT 25), 63% (41/65) of the HHCs (GMT 12), 41% of HCWs (GMT 6) and 13% (4/30) of pre-epidemic samples (GMT 6) for the pandemic influenza virus. Of the 32 confirmed cases, 60% had an antibody titre ≥ 40 for the pandemic strain, 53% for the A/swine/Iowa(H1N1) virus (GMT 62) and 43% for the A/swine/Texas(H3N2) virus (GMT 66). CONCLUSION: The antibody response to 2009 pandemic influenza virus was widespread in convalescence samples from patients with confirmed pandemic influenza infection but the GMT was below the protective titre. There was no evidence that antibodies to the swine influenza viruses had cross-protective effect against the 2009 pandemic influenza virus.
Assuntos
Anticorpos Antivirais/sangue , Formação de Anticorpos , Vírus da Influenza A Subtipo H1N1/imunologia , Influenza Humana/epidemiologia , Influenza Humana/imunologia , Pandemias , Adolescente , Adulto , Criança , Pré-Escolar , Proteção Cruzada , Reações Cruzadas , Feminino , Testes de Inibição da Hemaglutinação , Humanos , Lactente , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Adulto JovemRESUMO
A seasonal period of water deficit characterizes tropical dry forests (TDFs). There, sympatric tree species exhibit a diversity of growth rates, functional traits, and responses to drought, suggesting that each species may possess different strategies to grow under different conditions of water availability. The evaluation of the long-term growth responses to changes in the soil water balance should provide an understanding of how and when coexisting tree species respond to water deficit in TDFs. Furthermore, such differential growth responses may be linked to functional traits related to water storage and conductance. We used dendrochronology and climate data to retrospectively assess how the radial growth of seven coexisting deciduous tree species responded to the seasonal soil water balance in a Bolivian TDF. Linear mixed-effects models were used to quantify the relationships between basal area increment and seasonal water balance. We related these relationships with wood density and sapwood production to assess if they affect the growth responses to climate. The growth of all species responded positively to water balance during the wet season, but such responses differed among species as a function of their wood density. For instance, species with a strong growth response to water availability averaged a low wood density which may facilitate the storage of water in the stem. By contrast, species with very dense wood were those whose growth was less sensitive to water availability. Coexisting tree species thus show differential growth responses to changes in soil water balance during the wet season. Our findings also provide a link between wood density, a trait related to the ability of trees to store water in the stem, and wood formation in response to water availability.
Assuntos
Adaptação Fisiológica/fisiologia , Transpiração Vegetal/fisiologia , Árvores/crescimento & desenvolvimento , Clima Tropical , Madeira/fisiologia , Bolívia , Clima , Secas , Ecossistema , Água/fisiologia , Equilíbrio HidroeletrolíticoRESUMO
Estudiamos la riqueza y composición de especies vegetales en tres afloramientos rocosos (lajas) en Lomerío, Santa Cruz, Bolivia, dentro de un bosque seco tropical. Determinamos la variación de la vegetación desde el centro hacia el borde de las lajas, además que caracterizamos algunas especies propias de este hábitat. La riqueza de especies varía entre lajas, pero, en forma conjunta esta riqueza puede ser mayor a otros tipos de bosque aledaños a las lajas. La riqueza de especies fue mayor en el borde que en el centro de las lajas. En el borde de las lajas, la riqueza de especies varia según la distancia al centro de las lajas; la mayor riqueza se encontró en los primeros 10 m del borde. En el centro de las lajas Deuterocohnia meziana Kuntze ex Mez fue la especie más dominante, mientras que las especies más abundantes fueron D. meziana y Monvillea kroenleinii R. Kiesling. En el borde de las lajas Anthurium plowmanii Croat, Pseudananas sagenarius (Arruda) Camargo, Urera baccifera L., Casearia gossypiosperma Briq., Aspidosperma rigidum Rusby y Cereus tacuaralensis Cárdenas fueron las especies más abundantes. De acuerdo a las clases diamétricas, se puede considerar que existe regeneración natural para las principales especies arbóreas. Las lajas son hábitats muy importantes que deben considerarse dentro del manejo forestal de bosques naturales adyacentes, puesto que constituyen lugares de alta diversidad y endemismo de plantas y animales y que son refugios y fuentes de alimentación de muchas especies de animales.
Plant species richness and composition was studied on three rock outcrops (lajas) in a tropical dry forest in Lomerio, Bolivia. The variation in vegetation was determined from the center to the periphery of the influence of the rock outcrops and plant species indicators of rock outcrop habitats were identified. Species richness varied among lajas, but was higher in rock outcrop habitats compared to adjoining forests. Species richness was highest on the periphery of the rock outcrops compared to the vegetated islands on the center of the outcrop. The highest species richness was encountered 10 m from the vegetated border on the periphery of the pure rock surface. Deuterocohnia meziana Kuntze ex Mez was the most dominant (highest ground cover) plant species colonizing the center of the rock outcrops, while D. meziana and Monvillea kroenleinii R. Kiesling were the most abundant. On the periphery of the laja Anthurium plowmanii Croat, Pseudananas sagenarius (Arruda) Camargo, Urera baccifera L., Casearia gossypiosperma Briq., Aspidosperma rigidum Rusby and Cereus tacuaralensis Cárdenas were the most dominant species. Regeneration appears to be occurring for the principal tree species. Lajas are key habitats that should be considered in the natural management of forests in which they are imbedded. They constitute areas of high biodiversity and endemic species and are refuges and feeding areas for many animal species.