A Δ42PD1 fusion-expressing DNA vaccine elicits enhanced adaptive immune response to HIV-1: the key role of TLR4.
Virol J
; 19(1): 174, 2022 11 01.
Article
in English
| MEDLINE | ID: covidwho-2139345
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.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
HIV Infections
/
HIV-1
/
AIDS Vaccines
/
Vaccines, DNA
Topics:
Vaccines
Limits:
Animals
/
Humans
Language:
English
Journal:
Virol J
Journal subject:
Virology
Year:
2022
Document Type:
Article
Affiliation country:
S12985-022-01909-9
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