Passive immunization with llama single-domain antibody fragments reduces foot-and-mouth disease transmission between pigs

We aim to develop a method that confers rapid protection against foot-and-mouth disease (FMD) by passive immunization with recombinant llama single-domain antibody fragments (VHHs). Previously constructed genetic fusions of two VHHs (VHH2s) that either neutralizes FMDV or binds to porcine immunoglobulin to increase the serum half-life, conferred only limited protection to pigs. We therefore now generated VHH3s containing an additional FMDV binding VHH. Two VHH3s neutralized FMDV more potently than single VHHs and were highly produced by yeast cells. Injection of a mixture of these two VHH3s 24 h before FMD challenge infection of pigs reduced and delayed the development of clinical disease, viraemia and viral shedding. Furthermore, it significantly (P = 0.023) delayed FMD transmission. Thus, we have shown a proof of concept of passive FMD immunoprophylaxis using VHHs.