Pre-Existing Anti-Inflammatory Immune Conditions Influence Early Antibody Avidity and Isotype Profile Following Comirnaty® Vaccination in Mice

CASTILLO, MARIANGELES; MIRAGLIA, MARÍA C.; MANSILLA, FLORENCIA C.; RANDAZZO, CECILIA P.; BENTANCOR, LETICIA V.; FREIRE, TERESA; CAPOZZO, ALEJANDRA V.

Vaccines

MDPI

Lugar: BASEL; Año: 2025 vol. 13

Background/Objectives: Vaccine immunogenicity is often suboptimal in vulnerable populations such as the elderly, infants, and individuals in low- and middle-income countries. Onecontributing factor may be pre-existing immunomodulatory conditions, including helminthinfections. This study investigates the impact of Fasciola hepatica (F. hepatica) derivedmolecules on the early humoral response to the COVID-19 mRNA vaccine Comirnaty® ina 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 andantibody responses were assessed at 0, 14, and 21 days post-vaccination (dpv) throughserum analysis and ex vivo splenocyte stimulation with the SARS-CoV-2 receptor-bindingdomain (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-10upon RBD or LPS stimulation. At 21 dpv, FH-treated mice lacked IFN-γ production butmaintained 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 exhibitedreduced IgG avidity and a higher IgG1/IgG2 ratio. CFA-treated mice showed delayedavidity maturation. Conclusions: Prior exposure to F. hepatica antigens can modulate theearly immune response to Comirnaty®, affecting both cellular activation and antibodyquality. This altered response may reflect a reduced early protective capacity of the vaccine,which might need to be considered when designing or evaluating vaccination strategiesusing mRNA vaccines in helminth-endemic regions