Anti-VP6 VHH : an experimental treatment for rotavirus A-associated disease
- Autores
- Maffey, Lucia; Vega, Celina Guadalupe; Miño, Samuel; Garaicoechea, Lorena Laura; Parreño, Viviana
- Año de publicación
- 2016
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Species A Rotaviruses (RVA) remain a leading cause of mortality in children under 5 years of age. Current treatment options are limited. We assessed the efficacy of two VP6-specific llama-derived heavy chain antibody fragments (VHH) -2KD1 and 3B2- as an oral prophylactic and therapeutic treatment against RVA-induced diarrhea in a neonatal mouse model inoculated with virulent murine RVA (ECw, G16P[16]I7). Joint therapeutic administration of 2KD1+3B2 (200 μg/dose) successfully reduced diarrhea duration, RVA infection severity and virus shedding in feces. While the same dose of 2KD1 or 3B2 (200 μg) significantly reduced duration of RVA-induced diarrhea, 2KD1 was more effective in diminishing the severity of intestinal infection and RVA shedding in feces, perhaps because 2KD1 presented higher binding affinity for RVA particles than 3B2. Neither prophylactic nor therapeutic administration of the VHH interfered with the host’s humoral immune response against RVA. When 2KD1 (200 μg) was administered after diarrhea development, it also significantly reduced RVA intestinal infection and fecal shedding. Host antibody responses against the oral VHH treatment were not detected, nor did viral escape mutants. Our findings show that oral administration of anti-VP6 VHH constitute, not only an effective prophylactic treatment against RVA-associated diarrhea, but also a safe therapeutic tool against RVA infection, even once diarrhea is present. Anti-VP6 VHH could be used complementary to ongoing vaccination, especially in populations that have shown lower immunization efficacy. These VHH could also be scaled-up to develop pediatric medication or functional food like infant milk formulas that might help treat RVA diarrhea.
Inst.de Virología
Fil: Maffey, Lucia. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Vega, Celina Guadalupe. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Miño, Samuel. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina
Fil: Garaicoechea, Lorena Laura. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Parreño, Viviana. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina - Fuente
- PLoS One 11 (9) : e0162351. (2016)
- Materia
-
Rotavirus
Anticuerpos
Experimentación
Ensayos Clínicos
Antibodies
Experimentation
Clinical Trials - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- http://creativecommons.org/licenses/by-nc-sa/4.0/
- Repositorio
- Institución
- Instituto Nacional de Tecnología Agropecuaria
- OAI Identificador
- oai:localhost:20.500.12123/1046
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Anti-VP6 VHH : an experimental treatment for rotavirus A-associated diseaseMaffey, LuciaVega, Celina GuadalupeMiño, SamuelGaraicoechea, Lorena LauraParreño, VivianaRotavirusAnticuerposExperimentaciónEnsayos ClínicosAntibodiesExperimentationClinical TrialsSpecies A Rotaviruses (RVA) remain a leading cause of mortality in children under 5 years of age. Current treatment options are limited. We assessed the efficacy of two VP6-specific llama-derived heavy chain antibody fragments (VHH) -2KD1 and 3B2- as an oral prophylactic and therapeutic treatment against RVA-induced diarrhea in a neonatal mouse model inoculated with virulent murine RVA (ECw, G16P[16]I7). Joint therapeutic administration of 2KD1+3B2 (200 μg/dose) successfully reduced diarrhea duration, RVA infection severity and virus shedding in feces. While the same dose of 2KD1 or 3B2 (200 μg) significantly reduced duration of RVA-induced diarrhea, 2KD1 was more effective in diminishing the severity of intestinal infection and RVA shedding in feces, perhaps because 2KD1 presented higher binding affinity for RVA particles than 3B2. Neither prophylactic nor therapeutic administration of the VHH interfered with the host’s humoral immune response against RVA. When 2KD1 (200 μg) was administered after diarrhea development, it also significantly reduced RVA intestinal infection and fecal shedding. Host antibody responses against the oral VHH treatment were not detected, nor did viral escape mutants. Our findings show that oral administration of anti-VP6 VHH constitute, not only an effective prophylactic treatment against RVA-associated diarrhea, but also a safe therapeutic tool against RVA infection, even once diarrhea is present. Anti-VP6 VHH could be used complementary to ongoing vaccination, especially in populations that have shown lower immunization efficacy. These VHH could also be scaled-up to develop pediatric medication or functional food like infant milk formulas that might help treat RVA diarrhea.Inst.de VirologíaFil: Maffey, Lucia. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Vega, Celina Guadalupe. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Miño, Samuel. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; ArgentinaFil: Garaicoechea, Lorena Laura. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Parreño, Viviana. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina2017-08-25T16:57:20Z2017-08-25T16:57:20Z2016info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttp://hdl.handle.net/20.500.12123/1046http://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0162351&type=printableMaffey L, Vega CG, Miño S, Garaicoechea L, Parreño V (2016) Anti-VP6 VHH: An Experimental Treatment for Rotavirus A-Associated Disease. PLoS ONE 11(9): e0162351. https://doi.org/10.1371/journal.pone.0162351https://doi.org/10.1371/journal.pone.0162351PLoS One 11 (9) : e0162351. (2016)reponame:INTA Digital (INTA)instname:Instituto Nacional de Tecnología Agropecuariaenginfo:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by-nc-sa/4.0/Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)2025-09-29T13:44:09Zoai:localhost:20.500.12123/1046instacron:INTAInstitucionalhttp://repositorio.inta.gob.ar/Organismo científico-tecnológicoNo correspondehttp://repositorio.inta.gob.ar/oai/requesttripaldi.nicolas@inta.gob.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:l2025-09-29 13:44:09.491INTA Digital (INTA) - Instituto Nacional de Tecnología Agropecuariafalse |
dc.title.none.fl_str_mv |
Anti-VP6 VHH : an experimental treatment for rotavirus A-associated disease |
title |
Anti-VP6 VHH : an experimental treatment for rotavirus A-associated disease |
spellingShingle |
Anti-VP6 VHH : an experimental treatment for rotavirus A-associated disease Maffey, Lucia Rotavirus Anticuerpos Experimentación Ensayos Clínicos Antibodies Experimentation Clinical Trials |
title_short |
Anti-VP6 VHH : an experimental treatment for rotavirus A-associated disease |
title_full |
Anti-VP6 VHH : an experimental treatment for rotavirus A-associated disease |
title_fullStr |
Anti-VP6 VHH : an experimental treatment for rotavirus A-associated disease |
title_full_unstemmed |
Anti-VP6 VHH : an experimental treatment for rotavirus A-associated disease |
title_sort |
Anti-VP6 VHH : an experimental treatment for rotavirus A-associated disease |
dc.creator.none.fl_str_mv |
Maffey, Lucia Vega, Celina Guadalupe Miño, Samuel Garaicoechea, Lorena Laura Parreño, Viviana |
author |
Maffey, Lucia |
author_facet |
Maffey, Lucia Vega, Celina Guadalupe Miño, Samuel Garaicoechea, Lorena Laura Parreño, Viviana |
author_role |
author |
author2 |
Vega, Celina Guadalupe Miño, Samuel Garaicoechea, Lorena Laura Parreño, Viviana |
author2_role |
author author author author |
dc.subject.none.fl_str_mv |
Rotavirus Anticuerpos Experimentación Ensayos Clínicos Antibodies Experimentation Clinical Trials |
topic |
Rotavirus Anticuerpos Experimentación Ensayos Clínicos Antibodies Experimentation Clinical Trials |
dc.description.none.fl_txt_mv |
Species A Rotaviruses (RVA) remain a leading cause of mortality in children under 5 years of age. Current treatment options are limited. We assessed the efficacy of two VP6-specific llama-derived heavy chain antibody fragments (VHH) -2KD1 and 3B2- as an oral prophylactic and therapeutic treatment against RVA-induced diarrhea in a neonatal mouse model inoculated with virulent murine RVA (ECw, G16P[16]I7). Joint therapeutic administration of 2KD1+3B2 (200 μg/dose) successfully reduced diarrhea duration, RVA infection severity and virus shedding in feces. While the same dose of 2KD1 or 3B2 (200 μg) significantly reduced duration of RVA-induced diarrhea, 2KD1 was more effective in diminishing the severity of intestinal infection and RVA shedding in feces, perhaps because 2KD1 presented higher binding affinity for RVA particles than 3B2. Neither prophylactic nor therapeutic administration of the VHH interfered with the host’s humoral immune response against RVA. When 2KD1 (200 μg) was administered after diarrhea development, it also significantly reduced RVA intestinal infection and fecal shedding. Host antibody responses against the oral VHH treatment were not detected, nor did viral escape mutants. Our findings show that oral administration of anti-VP6 VHH constitute, not only an effective prophylactic treatment against RVA-associated diarrhea, but also a safe therapeutic tool against RVA infection, even once diarrhea is present. Anti-VP6 VHH could be used complementary to ongoing vaccination, especially in populations that have shown lower immunization efficacy. These VHH could also be scaled-up to develop pediatric medication or functional food like infant milk formulas that might help treat RVA diarrhea. Inst.de Virología Fil: Maffey, Lucia. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Vega, Celina Guadalupe. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Miño, Samuel. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina Fil: Garaicoechea, Lorena Laura. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Parreño, Viviana. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina |
description |
Species A Rotaviruses (RVA) remain a leading cause of mortality in children under 5 years of age. Current treatment options are limited. We assessed the efficacy of two VP6-specific llama-derived heavy chain antibody fragments (VHH) -2KD1 and 3B2- as an oral prophylactic and therapeutic treatment against RVA-induced diarrhea in a neonatal mouse model inoculated with virulent murine RVA (ECw, G16P[16]I7). Joint therapeutic administration of 2KD1+3B2 (200 μg/dose) successfully reduced diarrhea duration, RVA infection severity and virus shedding in feces. While the same dose of 2KD1 or 3B2 (200 μg) significantly reduced duration of RVA-induced diarrhea, 2KD1 was more effective in diminishing the severity of intestinal infection and RVA shedding in feces, perhaps because 2KD1 presented higher binding affinity for RVA particles than 3B2. Neither prophylactic nor therapeutic administration of the VHH interfered with the host’s humoral immune response against RVA. When 2KD1 (200 μg) was administered after diarrhea development, it also significantly reduced RVA intestinal infection and fecal shedding. Host antibody responses against the oral VHH treatment were not detected, nor did viral escape mutants. Our findings show that oral administration of anti-VP6 VHH constitute, not only an effective prophylactic treatment against RVA-associated diarrhea, but also a safe therapeutic tool against RVA infection, even once diarrhea is present. Anti-VP6 VHH could be used complementary to ongoing vaccination, especially in populations that have shown lower immunization efficacy. These VHH could also be scaled-up to develop pediatric medication or functional food like infant milk formulas that might help treat RVA diarrhea. |
publishDate |
2016 |
dc.date.none.fl_str_mv |
2016 2017-08-25T16:57:20Z 2017-08-25T16:57:20Z |
dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
format |
article |
status_str |
publishedVersion |
dc.identifier.none.fl_str_mv |
http://hdl.handle.net/20.500.12123/1046 http://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0162351&type=printable Maffey L, Vega CG, Miño S, Garaicoechea L, Parreño V (2016) Anti-VP6 VHH: An Experimental Treatment for Rotavirus A-Associated Disease. PLoS ONE 11(9): e0162351. https://doi.org/10.1371/journal.pone.0162351 https://doi.org/10.1371/journal.pone.0162351 |
url |
http://hdl.handle.net/20.500.12123/1046 http://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0162351&type=printable https://doi.org/10.1371/journal.pone.0162351 |
identifier_str_mv |
Maffey L, Vega CG, Miño S, Garaicoechea L, Parreño V (2016) Anti-VP6 VHH: An Experimental Treatment for Rotavirus A-Associated Disease. PLoS ONE 11(9): e0162351. https://doi.org/10.1371/journal.pone.0162351 |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by-nc-sa/4.0/ Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) |
eu_rights_str_mv |
openAccess |
rights_invalid_str_mv |
http://creativecommons.org/licenses/by-nc-sa/4.0/ Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) |
dc.format.none.fl_str_mv |
application/pdf |
dc.source.none.fl_str_mv |
PLoS One 11 (9) : e0162351. (2016) reponame:INTA Digital (INTA) instname:Instituto Nacional de Tecnología Agropecuaria |
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tripaldi.nicolas@inta.gob.ar |
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