The anti-influenza M2e antibody response is promoted by XCR1 targeting in pig skin

Deloizy, Charlotte; Fossum, Even; Barnier-Quer, Christophe; Urien, Céline; Chrun, Tiphany; Duval, Audrey; Codjovi, Maelle; Bouguyon, Edwige; Maisonnasse, Pauline; Hervé, Pierre‐Louis; Barc, Céline; Boulesteix, Olivier; Pezant, Jérémy; Chevalier, Christophe; Collin, Nicolas; Dalod, Marc; Bogen, Bjarne; Bertho, Nicolas; Schwartz-Cornil, Isabelle

doi:10.1038/s41598-017-07372-9

Cited by 16 publications

(20 citation statements)

References 72 publications

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“…Indeed, in our study, the DNA-MLV prime–boost strategy potently favored the antibody response, and the response was promoted by XCR1 and CD11c targeting, and even in mucosa. XCR1-targeting appears to be particularly suitable to promote antibody response both in mice [24,53] and in pigs as previously shown by us [54]. It has also been proposed that XCR1-targeting with ligands that induce a slow internalization kinetics of XCR1 [53] allows a prolonged antigenic interaction, leading to efficient activation of the BCR.…”

Section: Discussionmentioning

confidence: 90%

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

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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.

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Section: Discussionmentioning

confidence: 90%

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

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“…Alternatively, XCR1 targeting, another receptor exclusively expressed by cDC1s across species, could also be used to successfully induce high anti-eGn IgG responses in sheep, as recently showed by us in pigs for promoting anti-influenza M2e IgG responses. 56 …”

Section: Discussionmentioning

confidence: 99%

A Rift Valley fever virus Gn ectodomain-based DNA vaccine induces a partial protection not improved by APC targeting

et al. 2018

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Rift Valley fever virus, a phlebovirus endemic in Africa, causes serious diseases in ruminants and humans. Due to the high probability of new outbreaks and spread to other continents where competent vectors are present, vaccine development is an urgent priority as no licensed vaccines are available outside areas of endemicity. In this study, we evaluated in sheep the protective immunity induced by DNA vaccines encoding the extracellular portion of the Gn antigen which was either or not targeted to antigen-presenting cells. The DNA encoding untargeted antigen was the most potent at inducing IgG responses, although not neutralizing, and conferred a significant clinical and virological protection upon infectious challenge, superior to DNA vaccines encoding the targeted antigen. A statistical analysis of the challenge parameters supported that the anti-eGn IgG, rather than the T-cell response, was instrumental in protection. Altogether, this work shows that a DNA vaccine encoding the extracellular portion of the Gn antigen confers substantial—although incomplete—protective immunity in sheep, a natural host with high preclinical relevance, and provides some insights into key immune correlates useful for further vaccine improvements against the Rift Valley fever virus.

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“…Immunization of Macaques with a rat antibody specific for Macaque CLEC9A resulted in strong anti-rat IgG antibody responses in the absence of adjuvant (93). In pigs, targeting the influenza antigen M2e to cDC1s by fusion to porcine XCL1 enhanced antibody responses in both naive and sero-positive animals (94). Also in pigs, targeting the influenza antigen nucleoprotein (NP) to CD11c induced strong antibody responses, although the responses were not enhanced compared to non-targeted controls (95).…”

Section: Translation To Clinical Medicinementioning

confidence: 99%

Targeting Conventional Dendritic Cells to Fine-Tune Antibody Responses

et al. 2019

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Dendritic cells (DCs) facilitate cross talk between the innate and adaptive immune system. They sense and phagocytose invading pathogens, and are not only capable of activating naïve T cells, but can also determine the polarization of T cell responses into different effector subtypes. Polarized T cells in turn have a crucial role in antibody class switching and affinity maturation, and consequently the quality of the resulting humoral immunity. Targeting vaccines to DCs thus provides a great deal of opportunities for influencing the humoral immune responses, by fine-tuning the T cell response as well as regulating antigen availability for B cells. In this review we aim to outline how different DC targeted vaccination strategies can be utilized to induce a desired humoral immune response. A range of factors, including route of vaccine administration, use of adjuvants, choice of DC subset and surface receptor to target have been reported to influence the resulting immune response and will be reviewed herein. Finally, we will discuss opportunities for designing improved vaccines and challenges with translating this knowledge into clinical or veterinary medicine.

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The anti-influenza M2e antibody response is promoted by XCR1 targeting in pig skin

Cited by 16 publications

References 72 publications

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

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

A Rift Valley fever virus Gn ectodomain-based DNA vaccine induces a partial protection not improved by APC targeting

Targeting Conventional Dendritic Cells to Fine-Tune Antibody Responses

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