PD1-based DNA vaccine amplifies HIV-1 GAG-specific CD8+ T cells in mice

Zhou, Jingying; Cheung, Allen Ka Loon; Tan, Zhiwu; Wang, Haibo; Yu, Wenbo; Du, Yanhua; Kang, Yuanxi; Lu, Xiaofan; Liu, Li; Yuen, Kwok‐Yung; Chen, Zhiwei

doi:10.1172/jci64704

Cited by 62 publications

(92 citation statements)

References 60 publications

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“…Vaccination was performed as described previously (13). For tumor inoculation, BALB/c or SCID mice were injected with a lethal dose of 5 Â 10 5 AB1, AB1-WT1, or AB1-GAG cells, whereas C57BL/6 mice received 5 Â 10 5 B16F10-GAG cells in the right hind flank subcutaneously.…”

Section: Mouse Immunization and Tumor Challengementioning

confidence: 99%

“…Flow cytometry analysis, Elispot, and serum ELISA for assessing p24-specific immune responses Cell surface and intracellular immunostaining, Elispot as well as ELISA were performed as previously described (13). CD8-specific tetramer against HIV-1 GAG p24 gagA-I epitope AMQMLKETI was used for assay (Beckman Coulter).…”

Section: Wt1- Gag- and Luciferase-expressing Mesothelioma And Melanmentioning

confidence: 99%

“…To test this hypothesis, we sought to determine the efficacy and immune correlates of protection of conventional tumor antigen WT1 DNA vaccines and a soluble PD-1 (sPD1)-based fusion DNA vaccine, namely sPD1-p24 fc , via in vivo electroporation (EP) delivery against malignant mesothelioma in immunocompetent BALB/c mice. The model xenoantigen p24 is derived from HIV capsid protein GAG (13). sPD1-p24 fc /EP DNA vaccination induces uniquely high frequency of antigen-specific CD8 þ T cells with broad reactivity, longterm memory, polyfunctionality, and cytotoxicity by targeting the p24 to DCs while triggering IL12 production and antigen cross-presentation (13).…”

Section: Introductionmentioning

confidence: 99%

“…The model xenoantigen p24 is derived from HIV capsid protein GAG (13). sPD1-p24 fc /EP DNA vaccination induces uniquely high frequency of antigen-specific CD8 þ T cells with broad reactivity, longterm memory, polyfunctionality, and cytotoxicity by targeting the p24 to DCs while triggering IL12 production and antigen cross-presentation (13). Using a malignant murine mesothelioma tumor engineered to express WT1 or GAG, we demonstrate that functional antigen-specific CD8 þ T cells are essential to achieve complete prevention and therapeutic cure of mesothelioma.…”

Section: Introductionmentioning

confidence: 99%

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Vaccine-Elicited CD8+ T Cells Cure Mesothelioma by Overcoming Tumor-Induced Immunosuppressive Environment

et al. 2014

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Eradicating malignant tumors by vaccine-elicited host immunity remains a major medical challenge. To date, correlates of immune protection remain unknown for malignant mesothelioma. In this study, we demonstrated that antigen-specific CD8 þ T-cell immune response correlates with the elimination of malignant mesothelioma by a model PD-1-based DNA vaccine. Unlike the nonprotective tumor antigen WT1-based DNA vaccines, the model vaccine showed complete and long-lasting protection against lethal mesothelioma challenge in immunocompetent BALB/c mice. Furthermore, it remained highly immunogenic in tumor-bearing animals and led to therapeutic cure of preexisting mesothelioma. T-cell depletion and adoptive transfer experiments revealed that vaccine-elicited CD8 þ T cells conferred to the protective efficacy in a dose-dependent way. Also, these CD8

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Section: Mouse Immunization and Tumor Challengementioning

confidence: 99%

Section: Wt1- Gag- and Luciferase-expressing Mesothelioma And Melanmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Vaccine-Elicited CD8+ T Cells Cure Mesothelioma by Overcoming Tumor-Induced Immunosuppressive Environment

et al. 2014

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“…The vaccination of mice with a plasmid encoding the PD1 soluble domain fused to the HIV gag p24 protein elicited high frequencies of gag-specific polyfunctional and cytotoxic CD8 + T cells. It is interesting to notice that this vaccination strategy elicited stronger responses than those elicited in mice vaccinated with the HIV gag p41-scFv DEC205 [138].…”

Section: Dendritic Cell Targetingmentioning

confidence: 99%

DNA Vaccines: How Much Have We Accomplished In The Last 25 Years?

Rosa¹

2015

J Vaccines Vaccin

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Vaccination has been the most efficacious way to combat infectious diseases in human history. Nevertheless, there are still a variety of pathogens for which vaccines are urgently needed. In the last 25 years, DNA vaccines emerged as promising in prophylactic and therapeutic settings. However, despite all the practical advantages, DNA vaccines face challenges in inducing potent antigen specific immune responses and protection in humans. In the last years, rational approaches to improve the efficacy of DNA vaccines were developed and include: modifications of plasmid basic design, use of next-generation delivery methods, addition of adjuvants in the formulation, improvement in immunization protocols and even targeting to dendritic cells. In this review, we will explore the advances and hurdles involved in the development of more potent DNA vaccines.

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Biodegradable Microrobots for DNA Vaccine Delivery

Chen

Tan

Pan

et al. 2023

Adv Healthcare Materials

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The delivery of nucleic acid vaccine to stimulate host immune responses against Coronavirus disease 2019 shows promise. However, nucleic acid vaccines have drawbacks, including rapid clearance and poor cellular uptake, that limit their therapeutic potential. Microrobots can be engineered to sustain vaccine release and further control the interactions with immune cells that are vital for robust vaccination. Here, the 3D fabrication of biocompatible and biodegradable microrobots via the two‐photon polymerization of gelatin methacryloyl (GelMA) and their proof‐of‐concept application for DNA vaccine delivery is reported. Programmed degradation and drug release by varying the local exposure dose in 3D laser lithography and further functionalized the GelMA microspheres with polyethyleneimine for DNA vaccine delivery to dendritic cell and primary cells is demonstrated. In mice, the DNA vaccine delivered by functionalized microspheres elicited fast, enhanced, and durable antigen expression, which may lead to prolonged protection. Furthermore, we demonstrated the maneuverability of microrobots by fabricating GelMA microspheres on magnetic skeletons. In conclusion, GelMA microrobots may provide an efficient vaccination strategy by controlling the expression duration of DNA vaccines.

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PD1-based DNA vaccine amplifies HIV-1 GAG-specific CD8+ T cells in mice

Cited by 62 publications

References 60 publications

Vaccine-Elicited CD8+ T Cells Cure Mesothelioma by Overcoming Tumor-Induced Immunosuppressive Environment

Vaccine-Elicited CD8+ T Cells Cure Mesothelioma by Overcoming Tumor-Induced Immunosuppressive Environment

DNA Vaccines: How Much Have We Accomplished In The Last 25 Years?

Biodegradable Microrobots for DNA Vaccine Delivery

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