Eduardo Fonseca Pinto
@fiocruz.br
Scopus Publications
- Efficacy of LaAg Vaccine Associated with Saponin Against Leishmania amazonensis Infection
Mirian França de Mello, Patrícia de Almeida Machado, Pollyanna Stephanie Gomes, Gabriel Oliveira-Silva, Monique Pacheco Duarte Carneiro, et al.
Vaccines, 2025
Background/Objectives: The total lysate of Leishmania amazonensis (LaAg) is one of the most extensively studied vaccine formulations against leishmaniasis. Despite demonstrating safety and immunogenicity when administered intramuscularly, LaAg has failed to show efficacy in clinical trials and, in some cases, has even been associated with an enhanced susceptibility to infection. Adjuvants, which are molecules or compounds added to antigens to enhance the immunogenicity or modulate the immune response, are frequently employed in vaccine studies. This study aimed to evaluate different adjuvants to improve the protective efficacy of LaAg in L.amazonensis infection using a BALB/c mouse model. Methods: BALB/c mice were immunized with LaAg in combination with various adjuvants. The delayed-type hypersensitivity (DTH) test was assessed by measuring the infected paw and was used to evaluate the immunogenicity and to determine the most effective adjuvant. The immune response was analyzed through flow cytometry, focusing on cytokine production, immune cell recruitment and lesion size, alongside the control of parasite load at the infection site. The expression levels of iNOS and TGF-β were quantified using RT-qPCR, while IgG1, IgG2a and IgE antibody levels were determined via ELISA. Results: Among the adjuvants tested, only saponin (SAP) elicited a significant DTH response following LaAg challenge. SAP enhanced the immunogenicity of LaAg, as evidenced by increased IFN-γ-producing CD4+ and CD8+ T cells in the draining lymph nodes at 18 h post-challenge. Additionally, SAP facilitated the recruitment of lymphocytes, macrophages, neutrophils and eosinophils to the infection site. Conclusions: The LaAg + SAP combination conferred partial protection, as demonstrated by a reduction in lesion size and the partial control of parasite load. In conclusion, the addition of SAP as an adjuvant to LaAg effectively modulates the immune response, enhancing the vaccine’s protective efficacy. These findings provide valuable insights into the development of improved vaccines against L.amazonensis infection. - Concomitant use of anti-leishmanial therapy and antibacterial prophylaxis reduces plasma LPS levels and improves several aspects of experimental Leishmania infantum infection in golden hamsters
Memorias do Instituto Oswaldo Cruz, 2025 - Crosslinked chitosan microparticles as a safe and efficient DNA carrier for intranasal vaccination against cutaneous leishmaniasis
Beatriz L.S. Costa Souza, Eduardo F. Pinto, Izabella P.S. Bezerra, Daniel C.O. Gomes, Ana Maria B. Martinez, et al.
Vaccine X, 2023 - Identification of Immunodominant Proteins of the Leishmania (Viannia) naiffi SubProteome as Pan-Specific Vaccine Targets against Leishmaniasis
Prisciliana Jesus-Oliveira, Luzinei Silva-Couto, Nathalia Pinho, André Teixeira Da Silva-Ferreira, Leonardo Saboia-Vahia, et al.
Vaccines, 2023
Leishmaniasis is a wide-spectrum disease caused by parasites from Leishmania genus. A well-modulated immune response that is established after the long-lasting clinical cure of leishmaniasis can represent a standard requirement for a vaccine. Previous studies demonstrated that Leishmania (Viannia) naiffi causes benign disease and its antigens induce well-modulated immune responses in vitro. In this work we aimed to identify the immunodominant proteins present in the soluble extract of L. naiffi (sLnAg) as candidates for composing a pan-specific anti-leishmaniasis vaccine. After immunoblotting using cured patients of cutaneous leishmaniasis sera and proteomics approaches, we identified a group of antigenic proteins from the sLnAg. In silico analyses allowed us to select mildly similar proteins to the host; in addition, we evaluated the binding potential and degree of promiscuity of the protein epitopes to HLA molecules and to B-cell receptors. We selected 24 immunodominant proteins from a sub-proteome with 328 proteins. Homology analysis allowed the identification of 13 proteins with the most orthologues among seven Leishmania species. This work demonstrated the potential of these proteins as promising vaccine targets capable of inducing humoral and cellular pan-specific immune responses in humans, which may in the future contribute to the control of leishmaniasis. - Increased levels of cortisol are associated with the severity of experimental visceral leishmaniasis in a leishmania (L.) infantumhamster model
Tayany de D. Barros-Gonçalves, Andrea F. Saavedra, Luzinei da Silva-Couto, Raquel P. Ribeiro-Romão, Milla Bezerra-Paiva, et al.
Plos Neglected Tropical Diseases, 2021
Background Several infectious diseases are associated with hypothalamic-pituitary-adrenal (HPA) axis disorders by elevating circulating glucocorticoids (GCs), which are known to have an immunosuppressive potential. We conducted this study in golden hamsters, a suitable model for human visceral leishmaniasis (VL), to investigate the relationship of Leishmania (L.) infantum infection on cortisol production and VL severity. Methods L. infantum-infected (n = 42) and uninfected hamsters (n = 30) were followed-up at 30, 120, and 180 days post-infection (dpi). Plasma cortisol was analyzed by radioimmunoassay and cytokines, inducible nitric oxide synthase (iNOS), and arginase by RT-qPCR. Results All hamsters showed splenomegaly at 180 dpi. Increased parasite burden was associated with higher arginase expression and lower iNOS induction. Cortisol levels were elevated in infected animals in all-time points evaluated. Except for monocytes, all other leucocytes showed a strong negative correlation with cortisol, while transaminases were positively correlated. Immunological markers as interleukin (IL)-6, IL-1β, IL-10, and transforming growth-factor-β (TGF-β) were positively correlated to cortisol production, while interferon-γ (IFN-γ) presented a negative correlation. A network analysis showed cortisol as an important knot linking clinical status and immunological parameters. Conclusions These results suggest that L. infantum increases the systemic levels of cortisol, which showed to be associated with hematological, biochemical, and immunological parameters associated to VL severity. - A Cytokine Network Balance Influences the Fate of Leishmania (Viannia) braziliensis Infection in a Cutaneous Leishmaniasis Hamster Model
Milla B. Paiva, Raquel Peralva Ribeiro-Romão, Larissa Resende-Vieira, Thais Braga-Gomes, Marcia P. Oliveira, et al.
Frontiers in Immunology, 2021
The golden hamster is a suitable model for studying cutaneous leishmaniasis (CL) due toLeishmania (Viannia) braziliensis.Immunopathological mechanisms are well established in theL. (L.) major-mouse model, in which IL-4 instructs a Th2 response towards progressive infection. In the present study, we evaluated the natural history ofL. braziliensisinfection from its first stages up to lesion establishment, with the aim of identifying immunological parameters associated with the disease outcome and parasitism fate. To this end, hamsters infected with 104, 105, or 106promastigotes were monitored during the first hours (4h, 24h), early (15 days, 30 days) and late (50 days) post-infection (pi) phases. Cytokines, iNOS and arginase gene expression were quantified in the established lesions by reverse transcription-quantitative PCR. Compared to the 105or 106groups, 104animals presented lower lesions sizes, less tissue damage, and lower IgG levels. Basal gene expression in normal skin was high for TGF-β, and intermediary for TNF, IL-6, and IL-4. At 4hpi, no cytokine induction was observed in the 104group, while an upregulation of IL-6, IL-10, and IL-4 was observed in the 106group. At 15dpi, lesion appearance was accompanied by an increased expression of all assessed cytokines, markedly in the 105and 106groups. Upregulation of all investigated cytokines was observed in the late phase, although less expressive in the 104group. IFN-γ was the depending variable influencing tissue damage, while IL-6 was associated to parasite load. The network correlating gene expression and clinical and laboratorial parameters indicated inoculum-independent associations at 15 and 30dpi. A strong positive network correlation was observed in the 104group, but not in the 105or 106groups. In conclusion, IL-4, IL-6, IL-10, and TGF-β are linked oL. braziliensisprogression. However, a balanced cytokine network is the key for an immune response able to reduce the ongoing infection and reduce pathological damage. - Leishmania (V.) braziliensis infection promotes macrophage autophagy by a LC3B-dependent and BECLIN1-independent mechanism
Thabata Lopes Alberto Duque, Thamires Christinne de Souza Lopes Cruz Serrão, Antônio José da Silva Gonçalves, Eduardo Fonseca Pinto, Manoel Paes Oliveira-Neto, et al.
Acta Tropica, 2021 - Development of real-time PCR assays for evaluation of immune response and parasite load in golden hamster (Mesocricetus auratus) infected by Leishmania (Viannia) braziliensis
Raquel Peralva Ribeiro-Romão, Andrea Franco Saavedra, Alda Maria Da-Cruz, Eduardo Fonseca Pinto, Otacilio C. Moreira
Parasites and Vectors, 2016 - Intranasal Vaccination with Leishmanial Antigens Protects Golden Hamsters (Mesocricetus auratus) Against Leishmania (Viannia) braziliensis Infection
Luzinei da Silva-Couto, Raquel Peralva Ribeiro-Romão, Andrea Franco Saavedra, Beatriz Lilian da Silva Costa Souza, Otacílio Cruz Moreira, et al.
Plos Neglected Tropical Diseases, 2015
Background Previous results have shown that oral and intranasal administration of particulate Leishmania (Leishmania) amazonensis antigens (LaAg) partially protects mice against L. amazonensis infection. However, vaccination studies on species of the subgenus Viannia, the main causative agent of cutaneous and mucosal leishmaniasis in the Americas, have been hampered by the lack of easy-to-handle bio-models that accurately mimic the human disease. Recently, we demonstrated that the golden hamster is an appropriate model for studying the immunopathogenesis of cutaneous leishmaniasis caused by L. (Viannia) braziliensis. Using the golden hamster model, our current study investigated whether the protective effect of intranasal immunisation with LaAg can be extended to L. braziliensis infection. Methodology/Principal Findings Golden hamsters vaccinated with either two intranasal (IN) doses of LaAg (10 µg) or two intramuscular doses of LaAg (20 µg) were challenged 2 weeks post-vaccination with L. braziliensis. The results showed that IN immunisation with LaAg significantly reduced lesion growth and parasitic load as well as serum IgG and IgG2 levels. At the experimental endpoint on day 114 post-infection, IN-immunised hamsters that were considered protected expressed IFN-γ and IL10 mRNA levels that returned to uninfected skin levels. In contrast to the nasal route, intramuscular (IM) immunisation failed to provide protection. Conclusions/Significance These results demonstrate for the first time that the nasal route of immunisation can induce cross protection against L. braziliensis infection. - Comparative evaluation of lesion development, tissue damage, and cytokine expression in golden hamsters (Mesocricetus auratus) infected by inocula with different Leishmania (Viannia) braziliensis concentrations
Raquel P. Ribeiro-Romão, Otacílio C. Moreira, Elvia Yaneth Osorio, Lea Cysne-Finkelstein, Adriano Gomes-Silva, et al.
Infection and Immunity, 2014
The golden hamster ( Mesocricetus auratus ) is a susceptible model to Leishmania ( Viannia ) spp.; however, available studies employ different infection protocols, which account for clinical and pathological presentation differences. Herein, L . ( V .) braziliensis preparations were standardized to contain 10 4 , 10 5 , or 10 6 parasites to determine an optimal inoculum that ensured cutaneous lesions without causing a disseminated infection in hamsters. Lesion development was followed for 105 days by size measurements, and skin, draining lymph node, spleen, and sera were investigated to check parasite load, spleen visceralization, cytokine expression, histopathological changes, and anti- Leishmania IgG levels. The lesion emergence time was inversely proportional to the parasite concentration in the inocula. Animals infected by 10 4 parasites presented nodular lesions, while those infected with 10 6 parasites often exhibited ulcerated lesions. The differences in the final lesion sizes were observed between 10 4 and 10 5 inocula or 10 4 and 10 6 inocula. High IFNG expression, anti- Leishmania IgG levels, and parasite load occurred independently of the inoculum used. A mild inflammatory skin involvement was observed in animals infected with 10 4 parasites, while extensive tissue damage and parasite spleen visceralization occurred with 10 5 and 10 6 parasites. These results indicate that inocula with different concentrations of parasites generate differences in the time of lesion emergence, clinical presentation, and systemic commitment, despite high and similar IFNG expression and parasite load. This suggests that a modulation in the immune response to different parasite numbers occurs in an early phase of the infection, which could dictate the establishment and magnitude of the chronic phase of the disease. - Vaccines: Progress and challenges for the control of preventable diseases
Acta Biologica Colombiana, 2011 - Nanostructured polymer and lipid carriers for sunscreen. Biological effects and skin permeation
P. D. Marcato, J. Caverzan, B. Rossi-Bergmann, E. F. Pinto, D. Machado, et al.
Journal of Nanoscience and Nanotechnology, 2011 - Semisolid formulation containing a nanoencapsulated sunscreen: Effectiveness, in vitro photostability and immune response
Karina Paese, Alessandro Jäger, Fernanda S. Poletto, Eduardo Fonseca Pinto, Bartira Rossi-Bergmann, et al.
Journal of Biomedical Nanotechnology, 2009 - Structure-activity relationship of antileishmanials neolignan analogues
Mário Aveniente, Eduardo F. Pinto, Lourivaldo S. Santos, Bartira Rossi-Bergmann, Lauro E.S. Barata
Bioorganic and Medicinal Chemistry, 2007 - Protection against cutaneous leishmaniasis by intranasal vaccination with lipophosphoglycan
Roberta Olmo Pinheiro, Eduardo Fonseca Pinto, Herbert Leonel de Matos Guedes, Orlando Augusto Agrellos Filho, Katherine Antunes de Mattos, et al.
Vaccine, 2007 - Intranasal delivery of naked DNA encoding the LACK antigen leads to protective immunity against visceral leishmaniasis in mice
Daniel Cláudio de Oliveira Gomes, Eduardo Fonseca Pinto, Luiz Dione Barbosa de Melo, Wallace Pacienza Lima, Vicente Larraga, et al.
Vaccine, 2007 - Hyperbaric oxygen therapy reduces the size of Leishmania amazonensis-induced soft tissue lesions in mice
Wagner Welber Arrais-Silva, Eduardo Fonseca Pinto, Bartira Rossi-Bergmann, Selma Giorgio
Acta Tropica, 2006 - TGF-β-associated enhanced susceptibility to leishmaniasis following intramuscular vaccination of mice with Leishmania amazonensis antigens
Roberta Olmo Pinheiro, Eduardo Fonseca Pinto, Janaina Ribeiro Correia Lopes, Herbert Leonel Matos Guedes, Regina Ferro Fentanes, et al.
Microbes and Infection, 2005 - Intranasal vaccination against cutaneous leishmaniasis with a particulated leishmanial antigen or DNA encoding LACK
Eduardo Fonseca Pinto, Roberta Olmo Pinheiro, Alice Rayol, Vicente Larraga, Bartira Rossi-Bergmann
Infection and Immunity, 2004 - The T-cell anergy induced by Leishmania amazonensis antigens is related with defective antigen presentation and apoptosis
Roberta O. Pinheiro, Eduardo F. Pinto, Alessandra B. Benedito, Ulisses G. Lopes, Bartira Rossi-Bergmann
Anais Da Academia Brasileira De Ciencias, 2004 - Interferon-gamma-inducing oral vaccination with Leishmania amazonensis antigens protects BALB/c and C57BL/6 mice against cutaneous leishmaniasis
Eduardo Fonseca Pinto, Marcelle de Mello Cortezia, Bartira Rossi-Bergmann
Vaccine, 2003
