Dendritic Cells in the Cross Hair for the Generation of Tailored Vaccines

Gornati, Laura; Zanoni, Ivan; Granucci, Francesca

doi:10.3389/fimmu.2018.01484

Cited by 17 publications

(14 citation statements)

References 187 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…There are additional aspects of delivery to consider for the efficacy of mRNA vaccines. 145 and Gornati et al 146 ), in vivo targeting to DCs of synthetic mRNA vaccines against infectious diseases is still in the early phase. Formulation design, optimization, and combination with adjuvants or surface molecules to target DCs after immunization might increase the potency of synthetic mRNA vaccines, given the central role of DCs in processing antigens and initiating antigen-specific adaptive immune responses.…”

Section: Self-amplifying Mrna Vaccinesmentioning

confidence: 99%

mRNA as a Transformative Technology for Vaccine Development to Control Infectious Diseases

et al. 2019

View full text Add to dashboard Cite

Section: Self-amplifying Mrna Vaccinesmentioning

confidence: 99%

mRNA as a Transformative Technology for Vaccine Development to Control Infectious Diseases

et al. 2019

View full text Add to dashboard Cite

“…In contrast, CLRs are specialized in the recognition of carbohydrates, through one or more carbohydrate recognition domains (CRDs). Depending on the receptors engaged, APCs display different maturation states and produce different inflammatory mediators that impact the following cellular and humoral responses (7, 8).…”

Section: Introductionmentioning

confidence: 99%

S-Layer Glycoprotein From Lactobacillus kefiri Exerts Its Immunostimulatory Activity Through Glycan Recognition by Mincle

et al. 2019

View full text Add to dashboard Cite

The development of new subunit vaccines has promoted the rational design of adjuvants able to induce a strong T-cell activation by targeting specific immune receptors. The S-layer is a (glyco)-proteinaceous envelope constituted by subunits that self-assemble to form a two-dimensional lattice that covers the surface of different species of Bacteria and Archaea . Due to their ability to self-assemble in solution, they are attractive tools to be used as antigen/hapten carriers or adjuvants. Recently, we have demonstrated that S-layer glycoprotein from Lactobacillus kefiri CIDCA 8348 (SLP-8348) enhanced the LPS-induced response on macrophages in a Ca 2+ -dependent manner, but the receptors involved in these immunomodulatory properties remain unknown. Therefore, we aim to determine the C-type lectin receptors (CLRs) recognizing this bacterial surface glycoprotein as well as to investigate the role of glycans in both the immunogenicity and adjuvant capacity of SLP-8348. Here, using a mild periodate oxidation protocol, we showed that loss of SLP-8348 glycan integrity impairs the cell-mediated immune response against the protein. Moreover, our data indicate that the adjuvant capacity of SLP-8348 is also dependent of the biological activity of the SLP-8348 glycans. In order to evaluate the CLRs involved in the interaction with SLP-8348 an ELISA-based method using CLR–hFc fusion proteins showed that SLP-8348 interacts with different CLRs such as Mincle, SingR3, and hDC-SIGN. Using BMDCs derived from CLR-deficient mice, we show that SLP-8348 uptake is dependent of Mincle. Furthermore, we demonstrate that the SLP-8348-induced activation of BMDCs as well as its adjuvant capacity relies on the presence of Mincle and its signaling adaptor CARD9 on BMDCs, since SLP-8348-activated BMDCs from Mincle −/− or CARD9 −/− mice were not capable to enhance OVA-specific response in CD4 + T cells purified from OT-II mice. These findings significantly contribute to the understanding of the role of glycans in the immunomodulation elicited by bacterial SLPs and generate a great opportunity in the search for new adjuvants derived from non-pathogenic microorganisms.

show abstract

“…DNA vaccines are particularly efficient at stimulating T-cell responses [17]. In addition, a huge body of literature indicates, yet mainly in mouse models, that targeting antigens to the most efficient antigen presenting cell (APC) type, i.e., conventional dendritic cells (cDCs), strongly enhances the magnitude and breadth of T-cell responses [18,19,20,21], including in the case of DNA vaccination [22,23,24,25]. With the goal to trigger broad T-cell responses against PRRSV with DNA vaccination, we expressed PRRSV antigens (PRRSV-AGs) containing conserved T-cell epitopes in vaccibody structures (VB), which are dimeric platforms designed to target antigens to cellular receptors [23,24,25], being here pig XCR1 and CD11c.…”

Section: Introductionmentioning

confidence: 99%

A DNA-Modified Live Vaccine Prime–Boost Strategy Broadens the T-Cell Response and Enhances the Antibody Response against the Porcine Reproductive and Respiratory Syndrome Virus

Bernelin-Cottet

Urien

Stubsrud³

et al. 2019

Viruses

View full text Add to dashboard Cite

The Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) induces reproductive disorders in sows and respiratory illnesses in growing pigs and is considered as one of the main pathogenic agents responsible for economic losses in the porcine industry worldwide. Modified live PRRSV vaccines (MLVs) are very effective vaccine types against homologous strains but they present only partial protection against heterologous viral variants. With the goal to induce broad and cross-protective immunity, we generated DNA vaccines encoding B and T antigens derived from a European subtype 1 strain that include T-cell epitope sequences known to be conserved across strains. These antigens were expressed either in a native form or in the form of vaccibodies targeted to the endocytic receptor XCR1 and CD11c expressed by different types of antigen-presenting cells (APCs). When delivered in skin with cationic nanoparticles and surface electroporation, multiple DNA vaccinations as a stand-alone regimen induced substantial antibody and T-cell responses, which were not promoted by targeting antigens to APCs. Interestingly, a DNA-MLV prime–boost strategy strongly enhanced the antibody response and broadened the T-cell responses over the one induced by MLV or DNA-only. The anti-nucleoprotein antibody response induced by the DNA-MLV prime–boost was clearly promoted by targeting the antigen to CD11c and XCR1, indicating a benefit of APC-targeting on the B-cell response. In conclusion, a DNA-MLV prime–boost strategy, by enhancing the potency and breadth of MLV vaccines, stands as a promising vaccine strategy to improve the control of PRRSV in infected herds.

show abstract

Dendritic Cells in the Cross Hair for the Generation of Tailored Vaccines

Cited by 17 publications

References 187 publications

mRNA as a Transformative Technology for Vaccine Development to Control Infectious Diseases

mRNA as a Transformative Technology for Vaccine Development to Control Infectious Diseases

S-Layer Glycoprotein From Lactobacillus kefiri Exerts Its Immunostimulatory Activity Through Glycan Recognition by Mincle

A DNA-Modified Live Vaccine Prime–Boost Strategy Broadens the T-Cell Response and Enhances the Antibody Response against the Porcine Reproductive and Respiratory Syndrome Virus

Contact Info

Product

Resources

About