Induction of T-cell response by a DNA vaccine encoding a novel HLA-A*0201 severe acute respiratory syndrome coronavirus epitope

ABSTRACT DNA vaccines induce humoral and cellular immune responses in animal models and humans. To analyze the immunogenicity of the severe acute respiratory syndrome (SARS) coronavirus (CoV), SARS-CoV, spike DNA vaccine and the immunoregulatory activity of interleukin-2 (IL-2), DNA vaccine plasmids pcDNA-S and pcDNA-IL-2 were constructed and inoculated into BALB/c mice with or without pcDNA-IL-2 by using three different immunization routes (the intramuscular route, electroporation, or the oral route with live attenuated Salmonella enterica serovar Typhimurium). The cellular and humoral immune responses were assessed by enzyme-linked immunosorbent assays, lymphocyte proliferation assays, enzyme-linked immunospot assays, and fluorescence-activated cell sorter analyses. The results showed that specific humoral and cellular immunities could be induced in mice by inoculating them with SARS-CoV spike DNA vaccine alone or by coinoculation with IL-2-expressing plasmids. In addition, the immune response levels in the coinoculation groups were significantly higher than those in groups receiving the spike DNA vaccine alone. The comparison between the three vaccination routes indicated that oral vaccination evoked a vigorous T-cell response and a weak response predominantly with subclass immunoglobulin G2a (IgG2a) antibody. However, intramuscular immunization evoked a vigorous antibody response and a weak T-cell response, and vaccination by electroporation evoked a vigorous response with a predominant subclass IgG1 antibody response and a moderate T-cell response. Our findings show that the spike DNA vaccine has good immunogenicity and can induce specific humoral and cellular immunities in BALB/c mice, while IL-2 plays an immunoadjuvant role and enhances the humoral and cellular immune responses. Different vaccination routes also evoke distinct immune responses. This study provides basic information for the design of DNA vaccines against SARS-CoV.

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An IL-15 adjuvant enhances the efficacy of a combined DNA vaccine against Brucella by increasing the CD8+ cytotoxic T cell response

Vaccine ◽

10.1016/j.vaccine.2009.12.076 ◽

2010 ◽

Vol 28 (12) ◽

pp. 2408-2415 ◽

Cited By ~ 18

Author(s):

Xi-Dan Hu ◽

Su-Ting Chen ◽

Jia-Yun Li ◽

Da-Hai Yu ◽

Yi-zhang ◽

...

Keyword(s):

T Cell ◽

Dna Vaccine ◽

Cell Response ◽

T Cell Response ◽

Cytotoxic T Cell

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Erratum to “Efficient Modulation of T–cell Response by Dual–mode, Single–carrier Delivery of Cytokine–targeted siRNA and DNA Vaccine to Antigen–presenting Cells”

Molecular Therapy ◽

10.1038/mt.2008.247 ◽

2009 ◽

Vol 17 (2) ◽

pp. 395

Keyword(s):

T Cell ◽

Dna Vaccine ◽

Cell Response ◽

Antigen Presenting Cells ◽

T Cell Response ◽

Dual Mode ◽

Single Carrier ◽

Antigen Presenting

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Leishmania donovani p36(LACK) DNA Vaccine Is Highly Immunogenic but Not Protective against Experimental Visceral Leishmaniasis

Infection and Immunity ◽

10.1128/iai.69.8.4719-4725.2001 ◽

2001 ◽

Vol 69 (8) ◽

pp. 4719-4725 ◽

Cited By ~ 114

Author(s):

Peter C. Melby ◽

Jue Yang ◽

Weiguo Zhao ◽

Luis E. Perez ◽

Jun Cheng

Keyword(s):

T Cell ◽

Visceral Leishmaniasis ◽

Dna Vaccine ◽

Cell Response ◽

Leishmania Donovani ◽

T Cell Response ◽

Vaccine Antigen ◽

Interleukin 4 ◽

Th1 Response

ABSTRACT The acquisition of immunity following subclinical or resolved infection with the intracellular parasite Leishmania donovani suggests that vaccination could prevent visceral leishmaniasis (VL). The LACK (Leishmania homolog of receptors for activated C kinase) antigen is of interest as a vaccine candidate for the leishmaniases because of its immunopathogenic role in murine L. major infection. Immunization of mice with a truncated (24-kDa) version of the 36-kDa LACK antigen, delivered in either protein or DNA form, was found previously to protect against cutaneous L. major infection by redirecting the early T-cell response away from a pathogenic interleukin-4 (IL-4) response and toward a protective Th1 response. The amino acid sequence of theLeishmania p36(LACK) antigen is highly conserved, but the efficacy of this vaccine antigen in preventing disease caused by strains other than L. major has not been determined. We investigated the efficacy of a p36(LACK) DNA vaccine against VL because of the serious nature of this form of leishmaniasis and because it was unclear whether the LACK vaccine would be effective in a model where there was not a dominant pathogenic IL-4 response. We demonstrate here that although the LACK DNA vaccine induced a robust parasite-specific Th1 immune response (IFN-γ but not IL-4 production) and primed for an in vivo T-cell response to inoculated parasites, it did not induce protection against cutaneous or systemic L. donovanichallenge. Coadministration of IL-12 DNA with the vaccine did not enhance the strong vaccine-induced Th1 response or augment a protective effect.

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CD4+ T Cells Induced by a DNA Vaccine: Immunological Consequences of Epitope-Specific Lysosomal Targeting

Journal of Virology ◽

10.1128/jvi.75.21.10421-10430.2001 ◽

2001 ◽

Vol 75 (21) ◽

pp. 10421-10430 ◽

Cited By ~ 49

Author(s):

Fernando Rodriguez ◽

Stephanie Harkins ◽

Jeffrey M. Redwine ◽

Jose M. de Pereda ◽

J. Lindsay Whitton

Keyword(s):

T Cells ◽

T Cell ◽

Dna Vaccine ◽

Cell Response ◽

T Cell Responses ◽

Lymphocytic Choriomeningitis ◽

Lymphocytic Choriomeningitis Virus ◽

T Cell Response ◽

Cell Responses ◽

Lysosomal Targeting

ABSTRACT Our previous studies have shown that targeting DNA vaccine-encoded major histocompatibility complex class I epitopes to the proteasome enhanced CD8+ T-cell induction and protection against lymphocytic choriomeningitis virus (LCMV) challenge. Here, we expand these studies to evaluate CD4+ T-cell responses induced by DNA immunization and describe a system for targeting proteins and minigenes to lysosomes. Full-length proteins can be targeted to the lysosomal compartment by covalent attachment to the 20-amino-acid C-terminal tail of lysosomal integral membrane protein-II (LIMP-II). Using minigenes encoding defined T-helper epitopes from lymphocytic choriomeningitis virus, we show that the CD4+T-cell response induced by the NP309–328 epitope of LCMV was greatly enhanced by addition of the LIMP-II tail. However, the immunological consequence of lysosomal targeting is not invariably positive; the CD4+ T-cell response induced by the GP61–80 epitope was almost abolished when attached to the LIMP-II tail. We identify the mechanism which underlies this marked difference in outcome. The GP61–80 epitope is highly susceptible to cleavage by cathepsin D, an aspartic endopeptidase found almost exclusively in lysosomes. We show, using mass spectrometry, that the GP61–80 peptide is cleaved between residues F74 and K75 and that this destroys its ability to stimulate virus-specific CD4+ T cells. Thus, the immunological result of lysosomal targeting varies, depending upon the primary sequence of the encoded antigen. We analyze the effects of CD4+ T-cell priming on the virus-specific antibody and CD8+ T-cell responses which are mounted after virus infection and show that neither response appears to be accelerated or enhanced. Finally, we evaluate the protective benefits of CD4+ T-cell vaccination in the LCMV model system; in contrast to DNA vaccine-induced CD8+ T cells, which can confer solid protection against LCMV challenge, DNA vaccine-mediated priming of CD4+ T cells does not appear to enhance the vaccinee's ability to combat viral challenge.

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Immunization with a Mixture of HIV Env DNA and VLP Vaccines Augments Induction of CD8 T Cell Responses

Journal of Biomedicine and Biotechnology ◽

10.1155/2010/497219 ◽

2010 ◽

Vol 2010 ◽

pp. 1-11 ◽

Cited By ~ 6

Author(s):

Ling Ye ◽

Zhiyuan Wen ◽

Ke Dong ◽

Lei Pan ◽

Zhigao Bu ◽

...

Keyword(s):

Immune Response ◽

T Cell ◽

Dna Vaccine ◽

Cell Response ◽

T Cell Responses ◽

Cd8 T Cell ◽

T Cell Response ◽

Antibody Responses ◽

Cell Responses ◽

Virus Like Particle

The immune response induced by immunization with HIV Env DNA and virus-like particle (VLP) vaccines was investigated. Immunization with the HIV Env DNA vaccine induced a strong CD8 T cell response but relatively weak antibody response against the HIV Env whereas immunization with VLPs induced higher levels of antibody responses but little CD8 T cell response. Interestingly, immunization with a mixture the HIV Env DNA and VLP vaccines induced enhanced CD8 T cell and antibody responses. Further, it was observed that the mixing of DNA and VLP vaccines during immunization is necessary for augmenting induction of CD8 T cell responses and such augmentation of CD8 T cell responses was also observed by mixing the HIV Env DNA vaccine with control VLPs. These results show that immunization with a mixture of DNA and VLP vaccines combines advantages of both vaccine platforms for eliciting high levels of both antibody and CD8 T cell responses.

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

Parasitology Research ◽

10.1007/s00436-015-4429-8 ◽

2015 ◽

Vol 114 (6) ◽

pp. 2333-2339 ◽

Cited By ~ 6

Author(s):

Zhangping Tan ◽

TaoLi Zhou ◽

Hong Zheng ◽

Yan Ding ◽

Wenyue Xu

Keyword(s):

T Cell ◽

Dna Vaccine ◽

Specific Antibody ◽

Cell Response ◽

Cd8 T Cell ◽

T Cell Response

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T Cell Responses Are Required for Protection from Clinical Disease and for Virus Clearance in Severe Acute Respiratory Syndrome Coronavirus-Infected Mice

Journal of Virology ◽

10.1128/jvi.01049-10 ◽

2010 ◽

Vol 84 (18) ◽

pp. 9318-9325 ◽

Cited By ~ 163

Author(s):

Jincun Zhao ◽

Jingxian Zhao ◽

Stanley Perlman

Keyword(s):

Immune Response ◽

T Cells ◽

T Cell ◽

Severe Acute Respiratory Syndrome ◽

Innate Immune Response ◽

Cell Response ◽

T Cell Response ◽

Innate Immune ◽

Clinical Disease ◽

Virus Clearance

ABSTRACT A dysregulated innate immune response and exuberant cytokine/chemokine expression are believed to be critical factors in the pathogenesis of severe acute respiratory syndrome (SARS), caused by a coronavirus (SARS-CoV). However, we recently showed that inefficient immune activation and a poor virus-specific T cell response underlie severe disease in SARS-CoV-infected mice. Here, we extend these results to show that virus-specific T cells, in the absence of activation of the innate immune response, were sufficient to significantly enhance survival and diminish clinical disease. We demonstrated that T cells are responsible for virus clearance, as intravenous adoptive transfer of SARS-CoV-immune splenocytes or in vitro-generated T cells to SCID or BALB/c mice enhanced survival and reduced virus titers in the lung. Enhancement of the number of virus-specific CD8 T cells by immunization with SARS-CoV peptide-pulsed dendritic cells also resulted in a robust T cell response, earlier virus clearance, and increased survival. These studies are the first to show that T cells play a crucial role in SARS-CoV clearance and that a suboptimal T cell response contributes to the pathological changes observed in SARS. They also provide a new approach to SARS vaccine design.

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A putative miRNA in the spike gene of SARS-CoV-2 has perfect sequence identity to both the forward and reverse complementary strands of hsa-mir-8055 involved in T-cell response to antigen

10.31219/osf.io/hyz89 ◽

2020 ◽

Cited By ~ 2

Author(s):

Luis María Vaschetto

Keyword(s):

T Cell ◽

Severe Acute Respiratory Syndrome ◽

Cell Response ◽

T Cell Response ◽

Spike Protein ◽

Seed Region ◽

Spike Gene ◽

Sequence Identity ◽

Perfect Sequence ◽

Perfect Complementarity

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), also known as COVID-19, encodes for a spike protein that is responsible for both attachment and membrane fusion, thereby being critical in the pathogenicity of this virus. Here, I report that a putative miRNA localized in the spike gene of SARS-CoV-2 matches to the forward strand of hsa-miR-8055, a miRNA expressed during T-cell response to antigen, and also binds with perfect complementarity to its seed region

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