A Δ42PD1 fusion-expressing DNA vaccine elicits enhanced adaptive immune response to HIV-1: the key role of TLR4
Abstract Since its discovery in the 1990s, the DNA vaccine has been of great interest because of its ability to elicit both humoral and cellular immune responses while showing relative advantages regarding producibility, stability and storage. However, when applied to human subjects, inadequate immu...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-11-01
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| Series: | Virology Journal |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12985-022-01909-9 |
| _version_ | 1798044593921458176 |
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| author | Lin Cheng Xian Tang Yun He Bin Ju Hui Wang |
| author_facet | Lin Cheng Xian Tang Yun He Bin Ju Hui Wang |
| author_sort | Lin Cheng |
| collection | DOAJ |
| description | Abstract Since its discovery in the 1990s, the DNA vaccine has been of great interest because of its ability to elicit both humoral and cellular immune responses while showing relative advantages regarding producibility, stability and storage. However, when applied to human subjects, inadequate immunogenicity remains as the greatest challenge for the practical use of DNA vaccines. In this study, we generated a DNA vaccine Δ42PD1-P24 encoding a fusion protein comprised of the HIV-1 Gag p24 antigen and the extracellular domain of murine Δ42PD1, a novel endogenous Toll-like receptor 4 (TLR4) agonist. Using a mouse model, we found that Δ42PD1-P24 DNA vaccine elicited a higher antibody response and an increased number of IFN-γ-producing CD4 and CD8 T cells. Moreover, mice with Δ42PD1-P24 DNA vaccination were protected from a subcutaneous challenge with murine mesothelioma cells expressing the HIV-1 p24 antigen. Importantly, the Δ42PD1-mediated enhancement of immune responses was not observed in TLR4 knockout mice. Collectively, these data demonstrate that the immunogenicity and efficacy of DNA vaccines could be improved by the fusion of the extracellular domain of Δ42PD1 to target the immunogen to dendritic cells. |
| first_indexed | 2024-04-11T23:06:35Z |
| format | Article |
| id | doaj.art-be1b13057f674dd690a2306cf9ef96fe |
| institution | Directory Open Access Journal |
| issn | 1743-422X |
| language | English |
| last_indexed | 2024-04-11T23:06:35Z |
| publishDate | 2022-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Virology Journal |
| spelling | doaj.art-be1b13057f674dd690a2306cf9ef96fe2022-12-22T03:58:00ZengBMCVirology Journal1743-422X2022-11-011911710.1186/s12985-022-01909-9A Δ42PD1 fusion-expressing DNA vaccine elicits enhanced adaptive immune response to HIV-1: the key role of TLR4Lin Cheng0Xian Tang1Yun He2Bin Ju3Hui Wang4Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People’s HospitalInstitute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People’s HospitalDepartment of Infectious Diseases, Shenzhen Third People’s HospitalInstitute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People’s HospitalDepartment of Infectious Diseases, Shenzhen Third People’s HospitalAbstract Since its discovery in the 1990s, the DNA vaccine has been of great interest because of its ability to elicit both humoral and cellular immune responses while showing relative advantages regarding producibility, stability and storage. However, when applied to human subjects, inadequate immunogenicity remains as the greatest challenge for the practical use of DNA vaccines. In this study, we generated a DNA vaccine Δ42PD1-P24 encoding a fusion protein comprised of the HIV-1 Gag p24 antigen and the extracellular domain of murine Δ42PD1, a novel endogenous Toll-like receptor 4 (TLR4) agonist. Using a mouse model, we found that Δ42PD1-P24 DNA vaccine elicited a higher antibody response and an increased number of IFN-γ-producing CD4 and CD8 T cells. Moreover, mice with Δ42PD1-P24 DNA vaccination were protected from a subcutaneous challenge with murine mesothelioma cells expressing the HIV-1 p24 antigen. Importantly, the Δ42PD1-mediated enhancement of immune responses was not observed in TLR4 knockout mice. Collectively, these data demonstrate that the immunogenicity and efficacy of DNA vaccines could be improved by the fusion of the extracellular domain of Δ42PD1 to target the immunogen to dendritic cells.https://doi.org/10.1186/s12985-022-01909-9DNA vaccineΔ42PD1TLR4Dendritic cellImmunogenicity |
| spellingShingle | Lin Cheng Xian Tang Yun He Bin Ju Hui Wang A Δ42PD1 fusion-expressing DNA vaccine elicits enhanced adaptive immune response to HIV-1: the key role of TLR4 Virology Journal DNA vaccine Δ42PD1 TLR4 Dendritic cell Immunogenicity |
| title | A Δ42PD1 fusion-expressing DNA vaccine elicits enhanced adaptive immune response to HIV-1: the key role of TLR4 |
| title_full | A Δ42PD1 fusion-expressing DNA vaccine elicits enhanced adaptive immune response to HIV-1: the key role of TLR4 |
| title_fullStr | A Δ42PD1 fusion-expressing DNA vaccine elicits enhanced adaptive immune response to HIV-1: the key role of TLR4 |
| title_full_unstemmed | A Δ42PD1 fusion-expressing DNA vaccine elicits enhanced adaptive immune response to HIV-1: the key role of TLR4 |
| title_short | A Δ42PD1 fusion-expressing DNA vaccine elicits enhanced adaptive immune response to HIV-1: the key role of TLR4 |
| title_sort | δ42pd1 fusion expressing dna vaccine elicits enhanced adaptive immune response to hiv 1 the key role of tlr4 |
| topic | DNA vaccine Δ42PD1 TLR4 Dendritic cell Immunogenicity |
| url | https://doi.org/10.1186/s12985-022-01909-9 |
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