Antigen targeting to APC: From mice to veterinary species

Álvarez, Belén; Poderoso, Teresa; Alonso, Fernando; Ezquerra, Ángel; Domı́nguez, Javier; Revilla, Concepción

doi:10.1016/j.dci.2013.04.021

Cited by 23 publications

(15 citation statements)

References 134 publications

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“…To our knowledge, previous reports on DC targeting of protein vaccines utilized mainly the intravenous route, less often the subcutaneous, the intranasal and the IM routes, and rarely the ID route (19). We speculated that the high bolus of AG in the small and confined ID compartment would favor the capture by the local DC, thus not offering advantage to CD11c targeting.…”

Section: Discussionmentioning

confidence: 99%

“…Consequently, when injected in pigs, VC were not uniquely targeted to cDC, which are the most potent AG-presenting cells and could have even been targeted to counterproductive cells, for instance monocyte-derived cells or even granulocytes. The variation in targeting selectivity across species might explain outcome differences of DC-targeting strategies between mice and large mammals (19). Thus more selective immunoreceptors could reveal to be better targets, such as XCR1 which is specifically expressed on cDC1 in all mammalian species investigated so far and for which we recently validated a suitable targeting tool (25).…”

Section: Discussionmentioning

confidence: 99%

“…The molecular DC targeting is usually achieved by endocytic receptor-specific monoclonal antibodies (mAb) that are covalently linked, or complexed, with AGs. In addition to over 100 promising preclinical studies conducted in mice or in vitro using human cells (18), few in vivo reports suggest that DC targeting could also be beneficial in large mammals such as in non-human primates, cattle, and pigs (19). In addition, the anatomical site where the DC-targeted AG is delivered could also impact on the shaping of the immune response, given the tissue composition in DC and other interfering cell types and the local specificity of the innate response.…”

Section: Introductionmentioning

confidence: 99%

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A Universal Influenza Vaccine Can Lead to Disease Exacerbation or Viral Control Depending on Delivery Strategies

et al. 2016

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The development of influenza A virus (IAV) vaccines, which elicits cross-strain immunity against seasonal and pandemic viruses is a major public health goal. As pigs are susceptible to human, avian, and swine-adapted IAV, they would be key targets of so called universal IAV vaccines, for reducing both the zoonotic risk and the economic burden in the swine industry. They also are relevant preclinical models. However, vaccination with conserved IAV antigens (AGs) in pigs was reported to elicit disease exacerbation. In this study, we assessed whether delivery strategies, i.e., dendritic cell (DC) targeting by the intradermal (ID) or intramuscular (IM) routes, impact on the outcome of the vaccination with three conserved IAV AGs (M2e, NP, and HA2) in pigs. The AGs were addressed to CD11c by non-covalent binding to biotinylated anti-CD11c monoclonal antibody. The CD11c-targeted AGs given by the ID route exacerbated disease. Conversely, CD11c-targeted NP injected by the IM route promoted T cell response compared to non-targeted NP. Furthermore, the conserved IAV AGs injected by the IM route, independently of DC targeting, induced both a reduction of viral shedding and a broader IgG response as compared to the ID route. Our findings highlight in a relevant animal species that the route of vaccine delivery impacts on the protection induced by conserved IAV AGs and on vaccine adverse effects. Finally, our results indicate that HA2 stands as the most promising conserved IAV AG for universal vaccine development.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A Universal Influenza Vaccine Can Lead to Disease Exacerbation or Viral Control Depending on Delivery Strategies

et al. 2016

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“…The present study also adds important data relevant for understanding porcine DC and MPS functions, which are useful for studies on host-pathogen interactions and for the rational design of powerful vaccines such as those targeting DC. To this end, a wide variety of receptors have been targeted in pigs, including MHC molecules, siglecs, TLRs, C-type lectin receptors, costimulatory molecules, and chemokine receptors, without clear information on receptor distribution (59). Furthermore, even if the distribution of targeted receptors is conserved between species, other peculiarities in the biology of the DC subset could modify the outcome of Ag delivery.…”

Section: Discussionmentioning

confidence: 99%

Characterization and Transcriptomic Analysis of Porcine Blood Conventional and Plasmacytoid Dendritic Cells Reveals Striking Species-Specific Differences

Auray¹,

Keller

Python³

et al. 2016

The Journal of Immunology

157

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Porcine dendritic cells (DCs) are relatively well characterized, but a clear-cut identification of all DC subsets combined with full transcriptional profiling was lacking, preventing an unbiased insight into the functional specializations of DC subsets. Using a large panel of Abs in multicolor flow cytometry, cell sorting, and RNA sequencing we identified and characterized the porcine equivalent of conventional DCs (cDC) 1 and cDC2 as well as plasmacytoid DCs (pDCs) in the peripheral blood of pigs. We demonstrate that cDC1 are CD135CD14CD172aCADM1wCD11R1 cells, cDC2 are CD135CD14CD172aCADM1CD115wCD11R1CD1 cells and pDCs are CD4CD135CD172aCD123CD303 cells. As described in other species, only cDC1 express BATF3 and XCR1, cDC2 express FCER1A and FCGR2B, and only pDCs express TCF4 and NRP1 Nevertheless, despite these cross-species conserved subset-specific transcripts, porcine pDCs differed from the species described so far in many expressed genes and transcriptomic profiling clustered pDCs more distantly from cDCs than monocytes. The response of porcine DC subsets to TLR ligands revealed that pDCs are by far the most important source of TNF-α, IL-12p40, and of course IFN-α, whereas cDCs are most efficient in MHC and costimulatory molecule expression. Nevertheless, upregulation of CD40 and CD86 in cDCs was critically influenced or even dependent on the presence of pDCs, particularly for TLR 7 and 9 ligands. Our data demonstrate that extrapolation of data on DC biology from one species to another has to be done with care, and it shows how functional details have evolved differentially in different species.

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“…Immunizing pigs against mouse IgG, an increase in the anti-mouse IgG titres was observed by targeting the antibody to TLR2 [223]. In this work, it was also shown that the in vitro proliferative response of PBMCs obtained from pigs immunized with mouse IgG was enhanced when restimulation was performed using an anti-TLR2 mouse monoclonal antibody comparing with restimulation with an isotype-matched control.…”

Section: Immunomodulation Through Tlr2 For Veterinary Vaccinesmentioning

confidence: 75%

Targeting TLR2 for Vaccine Development

Basto

Leitão

2014

Journal of Immunology Research

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Novel and more effective immunization strategies against many animal diseases may profit from the current knowledge on the modulation of specific immunity through stimulation of innate immune receptors. Toll-like receptor (TLR)2-targeting formulations, such as synthetic lipopeptides and antigens expressed in fusion with lipoproteins, have been shown to have built-in adjuvant properties and to be effective at inducing cellular and humoral immune mechanisms in different animal species. However, contradictory data has arisen concerning the profile of the immune response elicited. The benefits of targeting TLR2 for vaccine development are thus still debatable and more studies are needed to rationally explore its characteristics. Here, we resume the main features of TLR2 and TLR2-induced immune responses, focusing on what has been reported for veterinary animals.

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Antigen targeting to APC: From mice to veterinary species

Cited by 23 publications

References 134 publications

A Universal Influenza Vaccine Can Lead to Disease Exacerbation or Viral Control Depending on Delivery Strategies

A Universal Influenza Vaccine Can Lead to Disease Exacerbation or Viral Control Depending on Delivery Strategies

Characterization and Transcriptomic Analysis of Porcine Blood Conventional and Plasmacytoid Dendritic Cells Reveals Striking Species-Specific Differences

Targeting TLR2 for Vaccine Development

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