tetano
Editor, Senior Moderator
Vaccines (Basel)
. 2020 Oct 1;8(4):E570.
doi: 10.3390/vaccines8040570.
Genetic Co-Administration of Soluble PD-1 Ectodomains Modifies Immune Responses against Influenza A Virus Induced by DNA Vaccination
Pierre Tannig[SUP] 1 [/SUP], Antonia Sophia Peter[SUP] 1 [/SUP], Dennis Lapuente[SUP] 1 [/SUP], Stephan Klessing[SUP] 1 [/SUP], Anna Schmidt[SUP] 1 [/SUP], Dominik Damm[SUP] 1 [/SUP], Matthias Tenbusch[SUP] 1 [/SUP], Klaus ?berla[SUP] 1 [/SUP], Vladimir Temchura[SUP] 1 [/SUP]
Affiliations
Abstract
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[SUP]+[/SUP] T cell responses, decreased regulatory CD4[SUP]+[/SUP] 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.
Keywords: DNA adjuvants; DNA vaccine; checkpoint blockade; immunomodulation; influenza A; intramuscular electroporation; soluble PD-1; soluble PD-L1.
. 2020 Oct 1;8(4):E570.
doi: 10.3390/vaccines8040570.
Genetic Co-Administration of Soluble PD-1 Ectodomains Modifies Immune Responses against Influenza A Virus Induced by DNA Vaccination
Pierre Tannig[SUP] 1 [/SUP], Antonia Sophia Peter[SUP] 1 [/SUP], Dennis Lapuente[SUP] 1 [/SUP], Stephan Klessing[SUP] 1 [/SUP], Anna Schmidt[SUP] 1 [/SUP], Dominik Damm[SUP] 1 [/SUP], Matthias Tenbusch[SUP] 1 [/SUP], Klaus ?berla[SUP] 1 [/SUP], Vladimir Temchura[SUP] 1 [/SUP]
Affiliations
- PMID: 33019546
- DOI: 10.3390/vaccines8040570
Abstract
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[SUP]+[/SUP] T cell responses, decreased regulatory CD4[SUP]+[/SUP] 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.
Keywords: DNA adjuvants; DNA vaccine; checkpoint blockade; immunomodulation; influenza A; intramuscular electroporation; soluble PD-1; soluble PD-L1.