A Δ42PD1 fusion-expressing DNA vaccine elicits enhanced adaptive immune response to HIV-1: the key role of TLR4

Cheng，Lin1,3; Tang，Xian1; He，Yun2; Ju，Bin1,3; Wang，Hui2,3

2022-12-01

10.1186/s12985-022-01909-9

Virology Journal   Impact Factor & Quartile

1743-422X

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.

Dendritic cell DNA vaccine Immunogenicity TLR4 Δ42PD1

SCI

English

Corresponding

Shenzhen Science and Technology Innovation Program[JCYJ20180228162229889];Shenzhen Science and Technology Innovation Program[JCYJ20190809115617365];

Virology

Virology

WOS:000877698000001

BMC

2-s2.0-85141211013

Scopus

1.Institute for Hepatology,National Clinical Research Center for Infectious Disease,Shenzhen Third People’s Hospital,Shenzhen,Guangdong Province,518112,China
2.Department of Infectious Diseases,Shenzhen Third People’s Hospital,Shenzhen,Guangdong Province,518112,China
3.The Second Affiliated Hospital,School of Medicine,Southern University of Science and Technology,Shenzhen,Guangdong Province,518112,China

Cheng，Lin,Tang，Xian,He，Yun,et al. A Δ42PD1 fusion-expressing DNA vaccine elicits enhanced adaptive immune response to HIV-1: the key role of TLR4[J]. Virology Journal,2022,19(1).

Cheng，Lin,Tang，Xian,He，Yun,Ju，Bin,&Wang，Hui.(2022).A Δ42PD1 fusion-expressing DNA vaccine elicits enhanced adaptive immune response to HIV-1: the key role of TLR4.Virology Journal,19(1).

Cheng，Lin,et al."A Δ42PD1 fusion-expressing DNA vaccine elicits enhanced adaptive immune response to HIV-1: the key role of TLR4".Virology Journal 19.1(2022).