Evaluation of viral peptide targeting to porcine sialoadhesin using a porcine reproductive and respiratory syndrome virus vaccination-challenge model.
Targeting antigens to professional antigen presenting cells resident at the sites where effective immune responses are generated is a promising vaccination strategy. As such, targeting sialoadhesin (Sn)-expressing macrophages, abundantly present in spleen and lymph nodes where they appear to be strategically placed for antigen capture and processing, is recently gaining increased attention. Previously, we have shown that humoral immune responses to the model antigen human serum albumin can be enhanced by using a porcine Sn-specific monoclonal antibody to target the model antigen to Sn-expressing macrophages. To date however, no studies have been performed to evaluate whether targeted delivery of a pathogen-derived antigen can enhance the pathogen-specific immune response. Therefore, we selected a linear epitope on glycoprotein 4 of porcine reproductive and respiratory syndrome virus (PRRSV), which is known to be a target of virus-neutralizing antibodies. This paper reports on the targeted delivery of this viral peptide to porcine Sn-expressing macrophages and the evaluation of the subsequent immune response in a vaccination-challenge set-up. Four copies of the selected PRRSV epitope were genetically fused to a previously developed porcine Sn-targeting recombinant antibody or an irrelevant isotype control. Fusion proteins were shown to be efficiently purified from HEK293T cell supernatants and subsequently, only Sn-specific fusion proteins were shown to bind to and to be internalized into Sn-expressing cells. Subsequent immunizations with a single dose of the fusion proteins showed that peptide-specific immune responses and neutralizing antibody responses after PRRSV challenge were enhanced in animals receiving a single 500 μg intramuscular dose of the Sn-targeting fusion protein, although correlations between the two read-outs were hard to effectuate. Furthermore, a minor beneficial effect on viral clearance was observed. Together, these data show that viral peptide targeting to porcine Sn-expressing macrophages can improve the anti-viral immune response, although more research will be needed to further explore vaccination potential.
Laboratory of Virology, Department of Virology, Parasitology and Immunology, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium. Electronic address: Karen.Ooms@UGent.be.
Karen
K
Ooms
Hanne
H
Van Gorp
Sara
S
Botti
Tim
T
Van Gaever
Peter L
PL
Delputte
Hans J
HJ
Nauwynck
D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D010455:Peptides / Q000008:administration & dosage* / Q000276:immunology; D019318:Porcine Reproductive and Respiratory Syndrome / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D019316:Porcine respiratory and reproductive syndrome virus / Q000235:genetics / Q000276:immunology*; D063267:Sialic Acid Binding Ig-like Lectin 1 / Q000276:immunology*; D013552:Swine; D014611:Vaccination; D014765:Viral Vaccines / Q000008:administration & dosage* / Q000276:immunology
D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D010455:Peptides; D063267:Sialic Acid Binding Ig-like Lectin 1; D014765:Viral Vaccines
AUC; CD169; CHO cells expressing pSn; CHO-pSn; DC; GP4; GS; HSA; IPMA; LV; Lelystad virus; Macrophage; PRRSV; Sialoadhesin; Siglec-1; Sn; Targeting; VN; area under the curve; dendritic cell; glycine-serine; glycoprotein 4; human serum albumin; i.m.; immunoperoxidase monolayer assay; intramuscular; mAb; monoclonal antibody; pSn; porcine reproductive and respiratory syndrome virus; porcine sialoadhesin; sialoadhesin; virus-neutralizing