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sPD-1 |
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Vaxjo ID |
231 |
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Vaccine Adjuvant Name |
sPD-1 |
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Adjuvant VO ID |
VO_0005718
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Description |
A genetically encoded soluble form of the PD-1 immune checkpoint protein, designed to modulate immune responses when co-delivered with DNA vaccines |
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Stage of Development |
Research |
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Host Species for Testing |
Mouse |
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Components |
The DNA-vaccine was applied either alone or in combination with genetic adjuvants encoding the soluble ectodomains of programmed cell death protein-1 (sPD-1) or its ligand (sPD-L1). |
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Structure |
Encodes only the ectodomain of the PD-1 protein, used as plasmid DNA; lacks transmembrane and intracellular domains |
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Storage |
DNA constructs stored in standard lab conditions |
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Preparation |
sPD-1 plasmid DNA was co-electroporated intramuscularly using TriGrid® electroporation system with HA and NP plasmids |
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Dosage |
30–45 µg DNA total per injection; sPD-1 and antigen plasmids co-delivered in 60 µL per dose |
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Function |
Due to the low efficacy and the need for seasonal adaptation of currently licensed influenza A vaccines, the importance of alternative vaccination strategies is increasingly recognized. Considering that DNA vaccines can be rapidly manufactured and readily adapted with novel antigen sequences, genetic vaccination is a promising immunization platform. However, the applicability of different genetic adjuvants to this approach still represents a complex challenge. Immune checkpoints are a class of molecules involved in adaptive immune responses and germinal center reactions. In this study, we immunized mice by intramuscular electroporation with a DNA-vaccine encoding hemagglutinin (HA) and nucleoprotein (NP) of the influenza A virus. The DNA-vaccine was applied either alone or in combination with genetic adjuvants encoding the soluble ectodomains of programmed cell death protein-1 (sPD-1) or its ligand (sPD-L1). Co-administration of genetic checkpoint adjuvants did not significantly alter immune responses against NP. In contrast, sPD-1 co-electroporation elevated HA-specific CD4+ T cell responses, decreased regulatory CD4+ T cell pools, and modulated the IgG2a-biased HA antibody pattern towards an isotype-balanced IgG response with a trend to higher influenza neutralization in vitro. Taken together, our data demonstrate that a genetic DNA-adjuvant encoding soluble ectodomains of sPD-1 was able to modulate immune responses induced by a co-administered influenza DNA vaccine. |
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Safety |
Well-tolerated in mice; no adverse effects reported; improves immune profile without apparent toxicity |
| References |
Tannig et al., 2020: Tannig P, Peter AS, Lapuente D, Klessing S, Schmidt A, Damm D, Tenbusch M, Ãœberla K, Temchura V. Genetic Co-Administration of Soluble PD-1 Ectodomains Modifies Immune Responses against Influenza A Virus Induced by DNA Vaccination. Vaccines. 2020; 8(4); . [PubMed: 33019546].
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