Pre-existing anti-inflammatory immune conditions influence early antibody avidity and isotype profile following Comirnaty® vaccination in mice
Background/Objectives: Vaccine immunogenicity is often suboptimal in vulnerable populations such as the elderly, infants, and individuals in low- and middle-income countries. One contributing factor may be pre-existing immunomodulatory conditions, including helminth infections. This study investigat...
| Autores principales: | , , , , , , |
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| Formato: | Artículo |
| Lenguaje: | Inglés |
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MDPI
2025
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| Materias: | |
| Acceso en línea: | http://hdl.handle.net/20.500.12123/23059 https://www.mdpi.com/2076-393X/13/7/677 https://doi.org/10.3390/vaccines13070677 |
| _version_ | 1855487059257458688 |
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| author | Castillo, Mariangeles Miraglia, Maria Cruz Mansilla, Florencia Celeste Randazzo, Cecilia Paola Bentancor, Leticia Veronica Freire, Teresa Capozzo, Alejandra |
| author_browse | Bentancor, Leticia Veronica Capozzo, Alejandra Castillo, Mariangeles Freire, Teresa Mansilla, Florencia Celeste Miraglia, Maria Cruz Randazzo, Cecilia Paola |
| author_facet | Castillo, Mariangeles Miraglia, Maria Cruz Mansilla, Florencia Celeste Randazzo, Cecilia Paola Bentancor, Leticia Veronica Freire, Teresa Capozzo, Alejandra |
| author_sort | Castillo, Mariangeles |
| collection | INTA Digital |
| description | Background/Objectives: Vaccine immunogenicity is often suboptimal in vulnerable populations such as the elderly, infants, and individuals in low- and middle-income countries. One contributing factor may be pre-existing immunomodulatory conditions, including helminth infections. This study investigates the impact of Fasciola hepatica (F. hepatica) derived molecules on the early humoral response to the COVID-19 mRNA vaccine Comirnaty® in a mouse model. Methods: BALB/c mice were pretreated with a F. hepatica protein extract (FH) or complete Freund’s adjuvant (CFA) prior to vaccination. Cytokine production and antibody responses were assessed at 0, 14, and 21 days post-vaccination (dpv) through serum analysis and ex vivo splenocyte stimulation with the SARS-CoV-2 receptor-binding domain (RBD) or LPS. Results: At 0 dpv, FH-treated mice showed increased serum IL-10, while CFA treatment induced IL-12. FH- but not CFA-treated splenocytes secreted IL-10 upon RBD or LPS stimulation. At 21 dpv, FH-treated mice lacked IFN-γ production but maintained IL-10 and showed elevated IL-4, consistent with a Th2-skewed profile. Although total anti-RBD IgG levels were similar between groups, FH-treated mice exhibited reduced IgG avidity and a higher IgG1/IgG2 ratio. CFA-treated mice showed delayed avidity maturation. Conclusions: Prior exposure to F. hepatica antigens can modulate the early immune response to Comirnaty®, affecting both cellular activation and antibody quality. This altered response may reflect a reduced early protective capacity of the vaccine, which might need to be considered when designing or evaluating vaccination strategies using mRNA vaccines in helminth-endemic regions. |
| format | Artículo |
| id | INTA23059 |
| institution | Instituto Nacional de Tecnología Agropecuaria (INTA -Argentina) |
| language | Inglés |
| publishDate | 2025 |
| publishDateRange | 2025 |
| publishDateSort | 2025 |
| publisher | MDPI |
| publisherStr | MDPI |
| record_format | dspace |
| spelling | INTA230592025-07-17T12:19:58Z Pre-existing anti-inflammatory immune conditions influence early antibody avidity and isotype profile following Comirnaty® vaccination in mice Castillo, Mariangeles Miraglia, Maria Cruz Mansilla, Florencia Celeste Randazzo, Cecilia Paola Bentancor, Leticia Veronica Freire, Teresa Capozzo, Alejandra Immunomodulation Immune Response Antiinflammatory Agents Antibodies Isotypes Vaccination Mice Inmunomodulación Respuesta Inmunológica Antinflamatorios Anticuerpos Isotipo Vacunación Ratón Fasciola hepatica Background/Objectives: Vaccine immunogenicity is often suboptimal in vulnerable populations such as the elderly, infants, and individuals in low- and middle-income countries. One contributing factor may be pre-existing immunomodulatory conditions, including helminth infections. This study investigates the impact of Fasciola hepatica (F. hepatica) derived molecules on the early humoral response to the COVID-19 mRNA vaccine Comirnaty® in a mouse model. Methods: BALB/c mice were pretreated with a F. hepatica protein extract (FH) or complete Freund’s adjuvant (CFA) prior to vaccination. Cytokine production and antibody responses were assessed at 0, 14, and 21 days post-vaccination (dpv) through serum analysis and ex vivo splenocyte stimulation with the SARS-CoV-2 receptor-binding domain (RBD) or LPS. Results: At 0 dpv, FH-treated mice showed increased serum IL-10, while CFA treatment induced IL-12. FH- but not CFA-treated splenocytes secreted IL-10 upon RBD or LPS stimulation. At 21 dpv, FH-treated mice lacked IFN-γ production but maintained IL-10 and showed elevated IL-4, consistent with a Th2-skewed profile. Although total anti-RBD IgG levels were similar between groups, FH-treated mice exhibited reduced IgG avidity and a higher IgG1/IgG2 ratio. CFA-treated mice showed delayed avidity maturation. Conclusions: Prior exposure to F. hepatica antigens can modulate the early immune response to Comirnaty®, affecting both cellular activation and antibody quality. This altered response may reflect a reduced early protective capacity of the vaccine, which might need to be considered when designing or evaluating vaccination strategies using mRNA vaccines in helminth-endemic regions. Instituto de Virología Fil: Castillo, Mariangeles. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología e Innovaciones Tecnológicas; Argentina Fil: Castillo, Mariangeles. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Miraglia, María Cruz. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología e Innovaciones Tecnológicas; Argentina Fil: Miraglia, María Cruz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Mansilla, Florencia Celeste. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología e Innovaciones Tecnológicas; Argentina Fil: Mansilla, Florencia Celeste. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Randazzo, Cecilia Paola. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología e Innovaciones Tecnológicas; Argentina Fil: Randazzo, Cecilia Paola. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Bentancor, Leticia Veronica. Universidad Nacional de José Clemente Paz. Instituto de Estudios para el Desarrollo Productivo y la Innovación; Argentina Fil: Freire, Teresa. Universidad de La República. Facultad de Medicina. Unidad Académica Inmunobiología. Laboratorio de Inmunomodulación y Vacunas; Uruguay Fil: Capozzo, Alejandra. Universidad Abierta Interamericana. Centro de Altos Estudios en Ciencias Humanas y de la Salud (CAECIHS); Argentina Fil: Capozzo, Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina 2025-07-17T12:15:05Z 2025-07-17T12:15:05Z 2025-07 info:ar-repo/semantics/artículo info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://hdl.handle.net/20.500.12123/23059 https://www.mdpi.com/2076-393X/13/7/677 2076-393X https://doi.org/10.3390/vaccines13070677 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 MDPI Vaccines 13 (7) : 677 (July 2025) |
| spellingShingle | Immunomodulation Immune Response Antiinflammatory Agents Antibodies Isotypes Vaccination Mice Inmunomodulación Respuesta Inmunológica Antinflamatorios Anticuerpos Isotipo Vacunación Ratón Fasciola hepatica Castillo, Mariangeles Miraglia, Maria Cruz Mansilla, Florencia Celeste Randazzo, Cecilia Paola Bentancor, Leticia Veronica Freire, Teresa Capozzo, Alejandra Pre-existing anti-inflammatory immune conditions influence early antibody avidity and isotype profile following Comirnaty® vaccination in mice |
| title | Pre-existing anti-inflammatory immune conditions influence early antibody avidity and isotype profile following Comirnaty® vaccination in mice |
| title_full | Pre-existing anti-inflammatory immune conditions influence early antibody avidity and isotype profile following Comirnaty® vaccination in mice |
| title_fullStr | Pre-existing anti-inflammatory immune conditions influence early antibody avidity and isotype profile following Comirnaty® vaccination in mice |
| title_full_unstemmed | Pre-existing anti-inflammatory immune conditions influence early antibody avidity and isotype profile following Comirnaty® vaccination in mice |
| title_short | Pre-existing anti-inflammatory immune conditions influence early antibody avidity and isotype profile following Comirnaty® vaccination in mice |
| title_sort | pre existing anti inflammatory immune conditions influence early antibody avidity and isotype profile following comirnaty r vaccination in mice |
| topic | Immunomodulation Immune Response Antiinflammatory Agents Antibodies Isotypes Vaccination Mice Inmunomodulación Respuesta Inmunológica Antinflamatorios Anticuerpos Isotipo Vacunación Ratón Fasciola hepatica |
| url | http://hdl.handle.net/20.500.12123/23059 https://www.mdpi.com/2076-393X/13/7/677 https://doi.org/10.3390/vaccines13070677 |
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