Anti-VP6 VHH : an experimental treatment for rotavirus A-associated disease
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 ag...
| Autores principales: | , , , , |
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| Formato: | info:eu-repo/semantics/article |
| Lenguaje: | Inglés |
| Publicado: |
2017
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| Acceso en línea: | 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 |
| _version_ | 1855034729455157248 |
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| author | Maffey, Lucia Vega, Celina Guadalupe Miño, Samuel Garaicoechea, Lorena Laura Parreño, Viviana |
| author_browse | Garaicoechea, Lorena Laura Maffey, Lucia Miño, Samuel Parreño, Viviana Vega, Celina Guadalupe |
| author_facet | Maffey, Lucia Vega, Celina Guadalupe Miño, Samuel Garaicoechea, Lorena Laura Parreño, Viviana |
| author_sort | Maffey, Lucia |
| collection | INTA Digital |
| 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. |
| format | info:eu-repo/semantics/article |
| id | INTA1046 |
| institution | Instituto Nacional de Tecnología Agropecuaria (INTA -Argentina) |
| language | Inglés |
| publishDate | 2017 |
| publishDateRange | 2017 |
| publishDateSort | 2017 |
| record_format | dspace |
| spelling | INTA10462018-02-21T16:25:33Z Anti-VP6 VHH : an experimental treatment for rotavirus A-associated disease Maffey, Lucia Vega, Celina Guadalupe Miño, Samuel Garaicoechea, Lorena Laura Parreño, Viviana Rotavirus Anticuerpos Experimentación Ensayos Clínicos Antibodies Experimentation Clinical Trials 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 2017-08-25T16:57:20Z 2017-08-25T16:57:20Z 2016 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion info:ar-repo/semantics/artículo 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 eng 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) application/pdf PLoS One 11 (9) : e0162351. (2016) |
| spellingShingle | Rotavirus Anticuerpos Experimentación Ensayos Clínicos Antibodies Experimentation Clinical Trials Maffey, Lucia Vega, Celina Guadalupe Miño, Samuel Garaicoechea, Lorena Laura Parreño, Viviana Anti-VP6 VHH : an experimental treatment for rotavirus A-associated disease |
| title | 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_short | Anti-VP6 VHH : an experimental treatment for rotavirus A-associated disease |
| title_sort | anti vp6 vhh an experimental treatment for rotavirus a associated disease |
| topic | Rotavirus Anticuerpos Experimentación Ensayos Clínicos Antibodies Experimentation Clinical Trials |
| 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 |
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