Immune protection against foot-and-mouth disease virus studied using virus-neutralizing and non-neutralizing concentrations of monoclonal antibodies

Abstract

Monoclonal antibodies (MAb) against sequential or conformational epitopes on foot-and-mouth disease virus (FMDV) passively protected neonatal syngeneic (BALB/c) mice at dilutions at which they could not neutralize virus infectivity in vitro. The B2, D9, 1C6 and 4C9 MAb, against the Group 1 (sequential) and Group 2 (conformational) epitopes, protected the mice at an antibody:virion molar ratio of between 38:1 and 84:1 (12-18 times lower than that required for neutralization of virus infectivity in vitro). The 3C8 (Group 3) and 6C3 (Group 4) MAb were, respectively, between 5 and 12 times, and between 18 and 40 times, less efficient at protection. There was no consistent correlation between the efficiency of neutralization of virus infectivity in vitro and the protection of neonatal mice against the virus pathogen. Thus, immune protection against FMDV must use mechanisms other than the direct neutralization of virus infectivity by antibody. Complement did not increase the virus neutralization titre of the MAb, but pepsin digestion of the MAb abrogated the enhanced in vivo protection over in vitro neutralization, with little effect on their capacity to neutralize virus infectivity. It is therefore likely that opsonization to a minimum affinity, and subsequent rapid phagocytosis, play a major role in the immune defence against FMDV. This is discussed in terms of the natural host for FMDV and the induction of immunological protection.