Background: Fasciola hepatica (F. hepatica) infection reduces antibody avidity to foot-and-mouth disease virus (FMDV) vaccination in cattle despite preserved total antibody levels. However, its effect on vaccine-induced immunity in water buffaloes (Bubalus bubalis), which contribute to FMDV maintenance in endemic settings, has not been investigated. Objectives: To evaluate the effect of natural F. hepatica infection on the magnitude and functional quality of the FMDV–specific antibody response in buffaloes under field conditions. Methods: Two buffalo herds (n = 50 each) were classified by infection status using coproparasitological analysis and serology. All animals were vaccinated within the national foot-and-mouth disease control programme, with the last dose administered 264 days before sampling. Serum neutralising titres, total antibodies by liquid-phase blocking ELISA, IgG levels, and IgG avidity to the A24/Cruzeiro vaccine strain were determined. Results: F. hepatica-infected buffaloes exhibited consistent decreases across all vaccine-induced antibody parameters. Neutralising titres were reduced approximately two-fold, IgG avidity by about 38 percent, IgG levels by about 36 percent, and liquid-phase blocking ELISA titres by about 1.6-fold compared with non-infected animals. Conclusions: This study provides the first field evidence that fasciolosis is associated with changes in the magnitude and quality of vaccine-induced humoral responses following FMDV vaccination in water buffaloes, indicating that F. hepatica infection may influence the interpretation of post-vaccination serological monitoring in this species under endemic field conditions.

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.