Corrigendum: Recent advances in antigen targeting to antigen-presenting cells in veterinary medicine.

[This corrects the article DOI: 10.3389/fimmu.2023.1080238.].

Recent advances in antigen targeting to antigen-presenting cells in veterinary medicine.

Advances in antigen targeting in veterinary medicine have gained traction over the years as an alternative approach for diseases that remain a challenge for traditional vaccines. In addition to the nature of the immunogen, antigen-targeting success relies heavily on the chosen receptor for its direct influence on the elicited response that will ensue after antigen uptake. Different approaches using antibodies, natural or synthetic ligands, fused proteins, and DNA vaccines have been explored in various veterinary species, with pigs, cattle, sheep, and poultry as the most frequent models. Antigen-presenting cells can be targeted using a generic approach, such as broadly expressed receptors such as MHC-II, CD80/86, CD40, CD83, etc., or focused on specific cell populations such as dendritic cells or macrophages (Langerin, DC-SIGN, XCR1, DC peptides, sialoadhesin, mannose receptors, etc.) with contrasting results. Interestingly, DC peptides show high specificity to DCs, boosting activation, stimulating cellular and humoral responses, and a higher rate of clinical protection. Likewise, MHC-II targeting shows consistent results in enhancing both immune responses; an example of this strategy of targeting is the approved vaccine against the bovine viral diarrhea virus in South America. This significant milestone opens the door to continuing efforts toward antigen-targeting vaccines to benefit animal health. This review discusses the recent advances in antigen targeting to antigen-presenting cells in veterinary medicine, with a special interest in pigs, sheep, cattle, poultry, and dogs.

Conjugated linoleic acid modifies transcriptional cytokine profile and induces early specific secretory IgA response in Giardia lamblia infected mice.

Objectives: Adaptive immunity is crucial in controlling Giardia lamblia infection in the intestinal mucosa, and some dietary lipids may improve mucosal immune function. The aim of this study was to evaluate conjugated linoleic acid (CLA) on the Th17/Treg response and secretory IgA production in a model of giardiasis infection. Materials and Methods: C3H/HeN male mice were infected with 5×106 G. lamblia trophozoites (GS/M-83-H7, ATCC collection). Mice were assigned randomly to experimental and control groups. CLA was administered to the experimental group and phosphate-buffered saline (PBS) was given to the control group. Parasite load kinetics was determined. Enzyme-linked immunosorbent assay (ELISA) was performed to evaluate IgA and cytokines. Nuclear transcription factors and cytokines were measured by RT-qPCR, and histology of small bowel cells was evaluated. Results: CLA administration reduced the parasite load (P<0.05) and increased early Giardia-specific secretory IgA production. CLA also increased the expression of interleukin-10, transforming growth factor (TGF)-ß, and inducible nitric oxide synthase (iNOS) (P<0.05), while infection elevated the expression of Foxp3, with a peak at 40 days post-infection (P<0.05). There were no pathological changes in the colonic mucosa due to infection or treatment. Thus, CLA stimulated mucosal immunity and enhanced the humoral response against G. lamblia, not only for early infection control but also to promote regulatory cytokine production at 40 dpi, restoring the intestinal balance after parasite elimination. Conclusion: Our findings reveal novel anti-parasitic effects through the immune-modulatory activity of CLA against the intestinal parasite G. lamblia.

Production of a full chimeric mouse x pig anti-porcine DEC205 receptor recombinant antibody.

Recombinant hybrid antibodies are commonly used in antigen-targeting assays to reduce the immunogenic potential associated with using classic mouse antibodies in other species. The DEC205 receptor has become an attractive target due to its effectiveness in activating the immune response and is considered a promising vaccination target. The aim of this study was to produce a fully chimeric mouse x pig anti-porcine DEC205 recombinant antibody (rAb). Based on a mouse anti-porcine DEC205 monoclonal antibody (mAb), we designed and expressed a chimeric mouse x pig rAb using the Expi293f system. The resulting rAb maintained the recognition capacity of the native mouse mAb toward the porcine DEC205 receptor, as evidenced by western blot analysis. By using flow cytometry, we evaluated the ability of the rAb to recognize DEC205+ dendritic cells. In conclusion, the chimeric mouse x pig anti-DEC205 rAb can be used in antigen-targeting assays as a vaccination strategy in pigs.

Analysis of Swine Conventional Dendritic Cells, DEC205+CD172a+/-CADM1+, from Blood and Spleen in Response to PRRSV and PEDV.

Conventional dendritic cells (cDCs) cannot be infected by porcine reproductive and respiratory syndrome virus (PRRSV) but respond to infection via cytokine production, indicating a possible role in initiation/regulation of the immune response against PRRSV. In this work, we evaluated the responses of splenic and blood cDCs, with DEC205+CADM1+CD172a+/- phenotype, as well as those of CD163+ cells against PRRSV and porcine epidemic diarrhea virus (PEDV). Both populations were incubated in the presence of PRRSV or PEDV with and without naïve CD3+ T cells, and cytokine responses were evaluated by qPCR and ELISA. Our results showed that cDCs, but not CD163+ cells, produced IL-12 in response to PRRSV. PEDV did not induce IL-12 production. Cocultures of cDCs and autologous naïve CD3+ cells resulted in decreased IL-12 production and low expression of IFN-γ transcripts in response to PRRSV. Interestingly, cDCs increased the proliferation of naïve T cells in the presence of PRRSV compared with that achieved with monocytes and peripheral blood mononuclear cells (PBMCs). Cocultures of CD163+ cells induced IL-10 and IL-4 expression in the presence of PRRSV and PEDV, respectively. In conclusion, cDCs can selectively produce IL-12 in response to PRRSV but poorly participate in the activation of naïve T cells.

Evaluation of a Recombinant Mouse X Pig Chimeric Anti-Porcine DEC205 Antibody Fused with Structural and Nonstructural Peptides of PRRS Virus.

Activation of the immune system using antigen targeting to the dendritic cell receptor DEC205 presents great potential in the field of vaccination. The objective of this work was to evaluate the immunogenicity and protectiveness of a recombinant mouse x pig chimeric antibody fused with peptides of structural and nonstructural proteins of porcine respiratory and reproductive syndrome virus (PRRSV) directed to DEC205+ cells. Priming and booster immunizations were performed three weeks apart and administered intradermally in the neck area. All pigs were challenged with PRRSV two weeks after the booster immunization. Immunogenicity was evaluated by assessing the presence of antibodies anti-PRRSV, the response of IFN-γ-producing CD4+ cells, and the proliferation of cells. Protection was determined by assessing the viral load in the blood, lungs, and tonsils using qRT-PCR. The results showed that the vaccine exhibited immunogenicity but conferred limited protection. The vaccine group had a lower viral load in the tonsils and a significantly higher production of antibodies anti-PRRSV than the control group (p < 0.05); the vaccine group also produced more CD4+IFN-γ+ cells in response to peptides from the M and Nsp2 proteins. In conclusion, this antigenized recombinant mouse x pig chimeric antibody had immunogenic properties that could be enhanced to improve the level of protection and vaccine efficiency.

Recombinant Antibodies in Veterinary Medicine: An Update.

The production of recombinant antibodies has had a tremendous impact on several research fields, most prominently in biotechnology, immunology and medicine, enabling enormous advances in each. Thus far, a broad diversity of recombinant antibody (rAb) forms have been designed and expressed using different expression systems. Even though the majority of rAbs approved for clinical use are targeted to humans, advances in veterinary medicine seem promising. The aim of this mini-review is to present an update regarding the rAbs in veterinary medicine reported to date, as well as their potential use in diagnostics, prophylaxis and therapeutics. Full- and single-chain fragment variables are the most common forms of rAbs developed for the detection, prevention and control of parasitic, bacterial and viral diseases, as well as pain and cancer treatment. Nonetheless, advances in research seem to be skewed toward economically important animals, such as pigs, cows, poultry and dogs. Although significant results have been obtained from the rAbs reported here, most have not been developed enough to be approved. Further research and clinical trials should be encouraged to enable important findings to fulfill their intended potential to improve animal well-being.