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Immunogenicity and Protective Efficacy of Influenza A DNA Vaccines Encoding Artificial Antigens Based on Conservative Hemagglutinin Stem Region and M2 Protein in Mice
Open AccessArticle

Genetic Co-Administration of Soluble PD-1 Ectodomains Modifies Immune Responses against Influenza A Virus Induced by DNA Vaccination

Institute of Clinical and Molecular Virology, Friedrich-Alexander-University Erlangen-Nürnberg, 91054 Erlangen, Germany
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Vaccines 2020, 8(4), 570; https://doi.org/10.3390/vaccines8040570
Received: 10 August 2020 / Revised: 22 September 2020 / Accepted: 23 September 2020 / Published: 1 October 2020
(This article belongs to the Special Issue Influenza Virus and Vaccine Development)
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. View Full-Text
Keywords: influenza A; DNA vaccine; DNA adjuvants; checkpoint blockade; soluble PD-1; soluble PD-L1; intramuscular electroporation; immunomodulation influenza A; DNA vaccine; DNA adjuvants; checkpoint blockade; soluble PD-1; soluble PD-L1; intramuscular electroporation; immunomodulation
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MDPI and ACS Style

Tannig, P.; Peter, A.S.; Lapuente, D.; Klessing, S.; Schmidt, A.; Damm, D.; Tenbusch, M.; Überla, 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, 570.

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