Pre-clinical antigenicity studies of an innovative multivalent vaccine for human visceral leishmaniasis

Autor: Laura Fernández, Shaden Kamhawi, Luigi Gradoni, Rhea N. Coler, Eugenia Carrillo, Jose M. Requena, Jesus G. Valenzuela, Begoña Pérez-Cabezas, Anabela Cordeiro-da-Silva, Fabiano Oliveira, Pedro Cecílio, Epifanio Fichera, Gaurav Gupta, Reinhard Glueck, Javier Moreno, Steven G. Reed
Přispěvatelé: European Commission, Unión Europea. Comisión Europea. 7 Programa Marco, European Regional Development Fund, National Institutes of Health (Estados Unidos), Instituto de Investigação e Inovação em Saúde
Rok vydání: 2017
Předmět:
0301 basic medicine
Male
Physiology
Antibodies
Protozoan
Lymphocyte Activation
Biochemistry
Leishmaniasis
Visceral/prevention & control
Immunologic Adjuvants
White Blood Cells
Mice
Immunogenicity
Vaccine
Animal Cells
Immune Physiology
Zoonoses
Medicine and Health Sciences
Public and Occupational Health
Immune Response
Leishmaniasis
Protozoans
Leishmania
Vaccines
Immunity
Cellular
Mice
Inbred BALB C
Immune System Proteins
Leishmaniasis Vaccines
T Cells
Immunogenicity
lcsh:Public aspects of medicine
Antibody Isotype Determination
Eukaryota
Vaccination and Immunization
Recombinant Proteins
3. Good health
Vaccination
Infectious Diseases
Leishmaniasis
Visceral
Cellular Types
Psychodidae/parasitology
Research Article
Neglected Tropical Diseases
Antigenicity
lcsh:Arctic medicine. Tropical medicine
Infectious Disease Control
lcsh:RC955-962
Immune Cells
Immunology
Antigens
Protozoan
Immunodominance
Biology
Research and Analysis Methods
Leishmaniasis Vaccines/immunology
03 medical and health sciences
Immune system
Antigen
Saliva/immunology
Adjuvants
Immunologic
Immunity
Parasitic Diseases
Adjuvants
Immunologic/administration & dosage
Animals
Humans
Antigens
Antibodies
Protozoan/blood
Saliva
Recombinant Proteins/immunology
Blood Cells
Protozoan Infections
Public Health
Environmental and Occupational Health
Organisms
Biology and Life Sciences
Proteins
lcsh:RA1-1270
Cell Biology
Tropical Diseases
Virology
Parasitic Protozoans
Leishmaniasis
Visceral/immunology
Immunity
Humoral
030104 developmental biology
Psychodidae/immunology
Immunologic Techniques
Antigens
Protozoan/immunology
Preventive Medicine
Psychodidae
Leishmania donovani
Zdroj: Digital.CSIC. Repositorio Institucional del CSIC
instname
PLoS Neglected Tropical Diseases, Vol 11, Iss 11, p e0005951 (2017)
Repositório Científico de Acesso Aberto de Portugal
Repositório Científico de Acesso Aberto de Portugal (RCAAP)
instacron:RCAAP
Repisalud
Instituto de Salud Carlos III (ISCIII)
PLoS Neglected Tropical Diseases
Popis: The notion that previous infection by Leishmania spp. in endemic areas leads to robust anti-Leishmania immunity, supports vaccination as a potentially effective approach to prevent disease development. Nevertheless, to date there is no vaccine available for human leishmaniasis. We optimized and assessed in vivo the safety and immunogenicity of an innovative vaccine candidate against human visceral leishmaniasis (VL), consisting of Virus-Like Particles (VLP) loaded with three different recombinant proteins (LJL143 from Lutzomyia longipalpis saliva as the vector-derived (VD) component, and KMP11 and LeishF3+, as parasite-derived (PD) antigens) and adjuvanted with GLA-SE, a TLR4 agonist. No apparent adverse reactions were observed during the experimental time-frame, which together with the normal hematological parameters detected seems to point to the safety of the formulation. Furthermore, measurements of antigen-specific cellular and humoral responses, generally higher in immunized versus control groups, confirmed the immunogenicity of the vaccine formulation. Interestingly, the immune responses against the VD protein were reproducibly more robust than those elicited against leishmanial antigens, and were apparently not caused by immunodominance of the VD antigen. Remarkably, priming with the VD protein alone and boosting with the complete vaccine candidate contributed towards an increase of the immune responses to the PD antigens, assessed in the form of increased ex vivo CD4+ and CD8+ T cell proliferation against both the PD antigens and total Leishmania antigen (TLA). Overall, our immunogenicity data indicate that this innovative vaccine formulation represents a promising anti-Leishmania vaccine whose efficacy deserves to be tested in the context of the “natural infection”.
European Community's
Databáze: OpenAIRE
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