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
INTA Digital (INTA)
Institución
Instituto Nacional de Tecnología Agropecuaria
OAI Identificador
oai:localhost:20.500.12123/1046
Acceder
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oai_identifier_str oai:localhost:20.500.12123/1046
network_acronym_str INTADig
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network_name_str INTA Digital (INTA)
spelling 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)2025-10-23T11:16:21Zoai: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:l2025-10-23 11:16:21.501INTA 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
reponame_str INTA Digital (INTA)
collection INTA Digital (INTA)
instname_str Instituto Nacional de Tecnología Agropecuaria
repository.name.fl_str_mv INTA Digital (INTA) - Instituto Nacional de Tecnología Agropecuaria
repository.mail.fl_str_mv tripaldi.nicolas@inta.gob.ar
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