Clinical and parasitological protection in a Leishmania infantum-macaque model vaccinated with adenovirus and the recombinant A2 antigen.
BACKGROUND: Visceral leishmaniasis (VL) is a severe vector-born disease of humans and dogs caused by Leishmania donovani complex parasites. Approximately 0.2 to 0.4 million new human VL cases occur annually worldwide. In the new world, these alarming numbers are primarily due to the impracticality o...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2014-06-01
|
| Series: | PLoS Neglected Tropical Diseases |
| Online Access: | http://europepmc.org/articles/PMC4063746?pdf=render |
| _version_ | 1819212743089061888 |
|---|---|
| author | Gabriel Grimaldi Antonio Teva Renato Porrozzi Marcelo A Pinto Renato S Marchevsky Maria Gabrielle L Rocha Miriam S Dutra Oscar Bruña-Romero Ana-Paula Fernandes Ricardo T Gazzinelli |
| author_facet | Gabriel Grimaldi Antonio Teva Renato Porrozzi Marcelo A Pinto Renato S Marchevsky Maria Gabrielle L Rocha Miriam S Dutra Oscar Bruña-Romero Ana-Paula Fernandes Ricardo T Gazzinelli |
| author_sort | Gabriel Grimaldi |
| collection | DOAJ |
| description | BACKGROUND: Visceral leishmaniasis (VL) is a severe vector-born disease of humans and dogs caused by Leishmania donovani complex parasites. Approximately 0.2 to 0.4 million new human VL cases occur annually worldwide. In the new world, these alarming numbers are primarily due to the impracticality of current control methods based on vector reduction and dog euthanasia. Thus, a prophylactic vaccine appears to be essential for VL control. The current efforts to develop an efficacious vaccine include the use of animal models that are as close to human VL. We have previously reported a L. infantum-macaque infection model that is reliable to determine which vaccine candidates are most worthy for further development. Among the few amastigote antigens tested so far, one of specific interest is the recombinant A2 (rA2) protein that protects against experimental L. infantum infections in mice and dogs. METHODOLOGY/PRINCIPAL FINDINGS: Primates were vaccinated using three rA2-based prime-boost immunization regimes: three doses of rA2 plus recombinant human interleukin-12 (rhIL-12) adsorbed in alum (rA2/rhIL-12/alum); two doses of non-replicative adenovirus recombinant vector encoding A2 (Ad5-A2) followed by two boosts with rA2/rhIL-12/alum (Ad5-A2+rA2/rhIL12/alum); and plasmid DNA encoding A2 gene (DNA-A2) boosted with two doses of Ad5-A2 (DNA-A2+Ad5-A2). Primates received a subsequent infectious challenge with L. infantum. Vaccines, apart from being safe, were immunogenic as animals responded with increased pre-challenge production of anti-A2-specific IgG antibodies, though with some variability in the response, depending on the vaccine formulation/protocol. The relative parasite load in the liver was significantly lower in immunized macaques as compared to controls. Protection correlated with hepatic granuloma resolution, and reduction of clinical symptoms, particularly when primates were vaccinated with the Ad5-A2+rA2/rhIL12/alum protocol. CONCLUSIONS/SIGNIFICANCE: The remarkable clinical protection induced by A2 in an animal model that is evolutionary close to humans qualifies this antigen as a suitable vaccine candidate against human VL. |
| first_indexed | 2024-12-23T06:47:49Z |
| format | Article |
| id | doaj.art-f9ec055b98584101997fe7a5317ddee3 |
| institution | Directory Open Access Journal |
| issn | 1935-2727 1935-2735 |
| language | English |
| last_indexed | 2024-12-23T06:47:49Z |
| publishDate | 2014-06-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Neglected Tropical Diseases |
| spelling | doaj.art-f9ec055b98584101997fe7a5317ddee32022-12-21T17:56:31ZengPublic Library of Science (PLoS)PLoS Neglected Tropical Diseases1935-27271935-27352014-06-0186e285310.1371/journal.pntd.0002853Clinical and parasitological protection in a Leishmania infantum-macaque model vaccinated with adenovirus and the recombinant A2 antigen.Gabriel GrimaldiAntonio TevaRenato PorrozziMarcelo A PintoRenato S MarchevskyMaria Gabrielle L RochaMiriam S DutraOscar Bruña-RomeroAna-Paula FernandesRicardo T GazzinelliBACKGROUND: Visceral leishmaniasis (VL) is a severe vector-born disease of humans and dogs caused by Leishmania donovani complex parasites. Approximately 0.2 to 0.4 million new human VL cases occur annually worldwide. In the new world, these alarming numbers are primarily due to the impracticality of current control methods based on vector reduction and dog euthanasia. Thus, a prophylactic vaccine appears to be essential for VL control. The current efforts to develop an efficacious vaccine include the use of animal models that are as close to human VL. We have previously reported a L. infantum-macaque infection model that is reliable to determine which vaccine candidates are most worthy for further development. Among the few amastigote antigens tested so far, one of specific interest is the recombinant A2 (rA2) protein that protects against experimental L. infantum infections in mice and dogs. METHODOLOGY/PRINCIPAL FINDINGS: Primates were vaccinated using three rA2-based prime-boost immunization regimes: three doses of rA2 plus recombinant human interleukin-12 (rhIL-12) adsorbed in alum (rA2/rhIL-12/alum); two doses of non-replicative adenovirus recombinant vector encoding A2 (Ad5-A2) followed by two boosts with rA2/rhIL-12/alum (Ad5-A2+rA2/rhIL12/alum); and plasmid DNA encoding A2 gene (DNA-A2) boosted with two doses of Ad5-A2 (DNA-A2+Ad5-A2). Primates received a subsequent infectious challenge with L. infantum. Vaccines, apart from being safe, were immunogenic as animals responded with increased pre-challenge production of anti-A2-specific IgG antibodies, though with some variability in the response, depending on the vaccine formulation/protocol. The relative parasite load in the liver was significantly lower in immunized macaques as compared to controls. Protection correlated with hepatic granuloma resolution, and reduction of clinical symptoms, particularly when primates were vaccinated with the Ad5-A2+rA2/rhIL12/alum protocol. CONCLUSIONS/SIGNIFICANCE: The remarkable clinical protection induced by A2 in an animal model that is evolutionary close to humans qualifies this antigen as a suitable vaccine candidate against human VL.http://europepmc.org/articles/PMC4063746?pdf=render |
| spellingShingle | Gabriel Grimaldi Antonio Teva Renato Porrozzi Marcelo A Pinto Renato S Marchevsky Maria Gabrielle L Rocha Miriam S Dutra Oscar Bruña-Romero Ana-Paula Fernandes Ricardo T Gazzinelli Clinical and parasitological protection in a Leishmania infantum-macaque model vaccinated with adenovirus and the recombinant A2 antigen. PLoS Neglected Tropical Diseases |
| title | Clinical and parasitological protection in a Leishmania infantum-macaque model vaccinated with adenovirus and the recombinant A2 antigen. |
| title_full | Clinical and parasitological protection in a Leishmania infantum-macaque model vaccinated with adenovirus and the recombinant A2 antigen. |
| title_fullStr | Clinical and parasitological protection in a Leishmania infantum-macaque model vaccinated with adenovirus and the recombinant A2 antigen. |
| title_full_unstemmed | Clinical and parasitological protection in a Leishmania infantum-macaque model vaccinated with adenovirus and the recombinant A2 antigen. |
| title_short | Clinical and parasitological protection in a Leishmania infantum-macaque model vaccinated with adenovirus and the recombinant A2 antigen. |
| title_sort | clinical and parasitological protection in a leishmania infantum macaque model vaccinated with adenovirus and the recombinant a2 antigen |
| url | http://europepmc.org/articles/PMC4063746?pdf=render |
| work_keys_str_mv | AT gabrielgrimaldi clinicalandparasitologicalprotectioninaleishmaniainfantummacaquemodelvaccinatedwithadenovirusandtherecombinanta2antigen AT antonioteva clinicalandparasitologicalprotectioninaleishmaniainfantummacaquemodelvaccinatedwithadenovirusandtherecombinanta2antigen AT renatoporrozzi clinicalandparasitologicalprotectioninaleishmaniainfantummacaquemodelvaccinatedwithadenovirusandtherecombinanta2antigen AT marceloapinto clinicalandparasitologicalprotectioninaleishmaniainfantummacaquemodelvaccinatedwithadenovirusandtherecombinanta2antigen AT renatosmarchevsky clinicalandparasitologicalprotectioninaleishmaniainfantummacaquemodelvaccinatedwithadenovirusandtherecombinanta2antigen AT mariagabriellelrocha clinicalandparasitologicalprotectioninaleishmaniainfantummacaquemodelvaccinatedwithadenovirusandtherecombinanta2antigen AT miriamsdutra clinicalandparasitologicalprotectioninaleishmaniainfantummacaquemodelvaccinatedwithadenovirusandtherecombinanta2antigen AT oscarbrunaromero clinicalandparasitologicalprotectioninaleishmaniainfantummacaquemodelvaccinatedwithadenovirusandtherecombinanta2antigen AT anapaulafernandes clinicalandparasitologicalprotectioninaleishmaniainfantummacaquemodelvaccinatedwithadenovirusandtherecombinanta2antigen AT ricardotgazzinelli clinicalandparasitologicalprotectioninaleishmaniainfantummacaquemodelvaccinatedwithadenovirusandtherecombinanta2antigen |