Oral isoprinosine enhances and sustains systemic and IgA-associated responses following intramuscular foot-and-mouth disease vaccination in mice and pigs

Abstract

Eliciting broad and durable vaccine-induced immunity without reformulating the established vaccines remains a practical challenge. Therefore, we evaluated oral isoprinosine (IP) as an independent adjunct to an experimental intramuscular bivalent inactivated foot-and-mouth disease (FMD) vaccine in mice and FMD-seronegative pigs. We investigated whether this regimen could sustain and prolong vaccine-associated immune responses, while retaining the original injectable formulation. Mice and FMD-seronegative pigs (n = 5/group) received an experimental bivalent inactivated FMD vaccine intramuscularly on 0 days post-vaccination (dpv) with oral IP independently. Structural protein-specific ELISA, virus-neutralizing titers to FMD virus (FMDV) serotypes O and A, IgA-associated readouts (serum and saliva), cytokine and receptor transcripts in porcine peripheral blood mononuclear cells (PBMCs), post-challenge survival and body-weight kinetics (mice), and serum biochemistry (pigs) were assessed over 84 dpv. Oral IP increased structural protein-specific ELISA responses and virus-neutralizing titers against FMDV serotypes O and A in both species. In mice, oral IP was associated with higher serum and salivary IgA-associated readouts (measured with commercial sIgA ELISA kits that are not FMDV antigen-specific), improved survival, and reduced body-weight loss after virulent FMDV challenge. In pigs, SP ELISA and virus-neutralizing antibody responses were higher in the oral IP group than in the vaccine-only control group across the 84-day observation period, accompanied by higher serum IgA-associated signals (non-antigen-specific) than in the vaccine-only control group; increased transcript levels of the cytokines IL-2, IL-4, IL-12p40, IL-17A, IL-18, IL-23p19, and IFN-γ, and of the cytokine receptor IL-23R, in PBMCs; and no treatment-related clinical or biochemical abnormalities. Orally administered IP enhanced and sustained the FMDV-specific systemic antibody responses and non-antigen-specific IgA-associated responses elicited by intramuscular FMD vaccination in mice and pigs, with the sustained enhancement most evident across the 84-day observation period in pigs. These findings support further evaluation of orally administered IP as an adjunct for maintaining vaccine responsiveness without reformulating the injectable vaccine.