Malaria DNA vaccine gp96NTD-CSP elicits both CSP-specific antibody and CD8+ T cell response

Tan, Zhangping; Zhou, Tong; Zheng, Hong; Ding, Yan; Xu, Wenyue

doi:10.1007/s00436-015-4429-8

Cited by 11 publications

(9 citation statements)

References 35 publications

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“…The lack of memory-stage protection by DNA-only vaccine-induced CD8 + T cells is consistent with the previous literature (52,53). Although DNA vaccines for malaria have shown some success in mice (54,55), such vaccines have historically been considered to be poorly immunogenic in humans (56)(57)(58). However, earlier studies were often limited by inefficient routes of DNA delivery (e.g., i.m.…”

Section: Discussionsupporting

confidence: 87%

Prime-and-Trap Malaria Vaccination To Generate Protective CD8+ Liver-Resident Memory T Cells

Olsen

Stone

Chuenchob

et al. 2018

The Journal of Immunology

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Tissue-resident memory CD8 T (Trm) cells in the liver are critical for long-term protection against pre-erythrocytic infection. Such protection can usually be induced with three to five doses of i.v. administered radiation-attenuated sporozoites (RAS). To simplify and accelerate vaccination, we tested a DNA vaccine designed to induce potent T cell responses against the SYVPSAEQI epitope of circumsporozoite protein. In a heterologous "prime-and-trap" regimen, priming using gene gun-administered DNA and boosting with one dose of RAS attracted expanding Ag-specific CD8 T cell populations to the liver, where they became Trm cells. Vaccinated in this manner, BALB/c mice were completely protected against challenge, an outcome not reliably achieved following one dose of RAS or following DNA-only vaccination. This study demonstrates that the combination of CD8 T cell priming by DNA and boosting with liver-homing RAS enhances formation of a completely protective liver Trm cell response and suggests novel approaches for enhancing T cell-based pre-erythrocytic malaria vaccines.

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Section: Discussionsupporting

confidence: 87%

Prime-and-Trap Malaria Vaccination To Generate Protective CD8+ Liver-Resident Memory T Cells

Olsen

Stone

Chuenchob

et al. 2018

The Journal of Immunology

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“…Moreover, studies have demonstrated that gp96 or its N-terminal domain activates macrophages and dendritic cells through interaction with Toll-like receptors (TLRs) and the induction of pro-inflammatory cytokines. It also activates specific T cells by cross-presentation of peptides to MHC class I and class II molecules (31). Therefore, gp96 as a genetic adjuvant creates a potent humoral and cellular immune responses by conferring antigen presentation by both MHC-I and MHC-II.…”

Section: Discussionmentioning

confidence: 99%

A DNA Vaccine Expressing Fusion Protein E2-NT(gp96) Induces Hepatitis C Virus Cross-Neutralizing Antibody in BALB/c Mice

et al. 2019

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Background: Development of an effective prophylactic vaccine is the optimal long-term goal for the eventual control of HCV infection. An effective HCV vaccine should be able to elicit neutralizing antibodies (NAbs). Glycoprotein E2 of HCV is the major target for NAbs. Methods: In this study, we designed and constructed a DNA vaccine (pcDNA-E2-NT(gp96)) encoding a fusion protein composed of HCV E2 ectodomain (genotype 1a) and N-terminal domain of gp96 as a biological adjuvant. Two possible forms of a fusion protein, namely E2-NT(gp96) and NT(gp96)-E2, were made and subjected to in silico modeling and analysis. After the selection of the best form and confirmation its expression capacity in COS-7 cells, recombinant pcDNA-E2-NT(gp96) plasmid was generated by cloning of target genes into pcDNA3.1(+) plasmid. Constructed DNA vaccine immunogenicity was evaluated in BALB/c mice by measurement specific antibodies by ELISA and their neutralization capacity by neutralization assay. Results: In silico modeling and analysis showed that the E2-NT(gp96) structure was more valid than NT(gp96)-E2. Docking result revealed that the selected fusion protein had a high tendency for interaction with the main receptor (CD81) of HCV. GFP expression in COS-7 cells confirmed the E2-NT(gp96) expression capacity. Restriction enzyme digestion and sequencing results confirmed the integrity of the constructed plasmid. ELISA results showed that the pcDNA-E2-NT(gp96) induced high titers of specific antibodies in immunized mice. The sera of immunized mice cross-neutralized JFH1/HCVcc genotype 2a by 55% relative to pre-immune sera. Conclusions: Total results showed that the generated DNA vaccine induced potent immune responses in immunized mice. Therefore, our findings are sufficiently encouraging to propose the pcDNA-E2-NT(gp96) as a promising vaccine candidate for HCV infection.

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“…It was suggested that tuberculosis may depend on the T helper-1 (Th1)-type cell-mediated immune response to protect against infection by an intracellular pathogen, including Brucella (24,25). A number of studies demonstrated that DNA vaccines acted on the major histocompatibility complex class I and II following naked DNA immunization, inducing a wide range of immune responses, including antibody production, CD8 cytotoxic T cells and CD4 T helper cell activation (10,23,26). DNA vaccines overcame the disadvantages of acellular vaccines, including recombinant proteins and synthetic peptides that were not adequately processed and presented, which resulted in a failure to induce a strong CMI response as well as to confer a high degree of protection (6,27).…”

Section: Discussionmentioning

confidence: 99%

Evaluation of a DNA vaccine encoding Brucella BvrR in BALB/c mice

et al. 2018

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Brucellosis is an important neglected zoonotic disease, and the pathogens responsible are Brucellae. In order to evaluate the immunogenicity and protective efficacy of a DNA vaccine encoding Brucella BvrR, the recombinant plasmid pCDNA-BvrR was constructed by inserting the BvrR gene fragment into a pCDNA3.0 vector. The His 6-tagged BvrR was purified with His-trap FF crude affinity chromatography and verified with an anti-histidine monoclonal antibody by western blot analysis. The specific immunoglobulin antigens and their isotypes were detected by indirect ELISA. The recombinant His 6-BvrR protein was expressed and purified by affinity chromatography. The optical density 450 value of immunoglobulin G (IgG) in the pCDNA-BvrR group was significantly increased compared with the pCDNA3.0 vector or PBS groups (P<0.05), and the pCDNA3.0 vector and PBS groups exhibited no significant difference (P>0.05). BvrR induced specific antibodies with a dominance of IgG2a over IgG1 and the T cell-proliferative response, in addition to a typical T helper-1 (Th1)-dominated immune response in mice. The splenocytes from mice of the pCDNA-BvrR group demonstrated significant proliferative activity compared with the pCDNA3.0 vector group. The present results indicated that immunization with BvrR induced a specific Th1-type immune response in mice. Subsequent to challenging with B. abortus S19, it was identified that the DNA vaccine pCDNA-BvrR induced a significant level of protection in BALB/c mice by evaluating systemic bacterial clearance. These results suggested that BvrR may be a good candidate for a DNA vaccine against brucellosis.

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Malaria DNA vaccine gp96NTD-CSP elicits both CSP-specific antibody and CD8+ T cell response

Cited by 11 publications

References 35 publications

Prime-and-Trap Malaria Vaccination To Generate Protective CD8+ Liver-Resident Memory T Cells

Prime-and-Trap Malaria Vaccination To Generate Protective CD8+ Liver-Resident Memory T Cells

A DNA Vaccine Expressing Fusion Protein E2-NT(gp96) Induces Hepatitis C Virus Cross-Neutralizing Antibody in BALB/c Mice

Evaluation of a DNA vaccine encoding Brucella BvrR in BALB/c mice

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