scholarly journals Designed DNA-Encoded IL-36 Gamma Acts as a Potent Molecular Adjuvant Enhancing Zika Synthetic DNA Vaccine-Induced Immunity and Protection in a Lethal Challenge Model

Vaccines ◽  
2019 ◽  
Vol 7 (2) ◽  
pp. 42 ◽  
Author(s):  
Lumena Louis ◽  
Megan C. Wise ◽  
Hyeree Choi ◽  
Daniel O. Villarreal ◽  
Kar Muthumani ◽  
...  
Keyword(s):  
Dna Vaccine ◽  
Critical Role ◽  
Lethal Challenge ◽  
Synthetic Dna ◽  
Molecular Adjuvant ◽  
Immunodeficiency Virus ◽  
Suboptimal Dose ◽  
Dose Sparing ◽  
Molecular Adjuvants ◽  
Induced Immunity

Identification of novel molecular adjuvants which can boost and enhance vaccine-mediated immunity and provide dose-sparing potential against complex infectious diseases and for immunotherapy in cancer is likely to play a critical role in the next generation of vaccines. Given the number of challenging targets for which no or only partial vaccine options exist, adjuvants that can address some of these concerns are in high demand. Here, we report that a designed truncated Interleukin-36 gamma (IL-36 gamma) encoded plasmid can act as a potent adjuvant for several DNA-encoded vaccine targets including human immunodeficiency virus (HIV), influenza, and Zika in immunization models. We further show that the truncated IL-36 gamma (opt-36γt) plasmid provides improved dose sparing as it boosts immunity to a suboptimal dose of a Zika DNA vaccine, resulting in potent protection against a lethal Zika challenge.

scholarly journals Molecular adjuvant IL-33 enhances the potency of a DNA vaccine in a lethal challenge model

Vaccine ◽  
2015 ◽  
Vol 33 (35) ◽  
pp. 4313-4320 ◽  
Author(s):  
Daniel O. Villarreal ◽  
Nikolaos Svoronos ◽  
Megan C. Wise ◽  
Devon J. Shedlock ◽  
Matthew P. Morrow ◽  
...  
Keyword(s):  
Dna Vaccine ◽  
Lethal Challenge ◽  
Molecular Adjuvant

scholarly journals Co-Administration of Molecular Adjuvants Expressing NF-Kappa B Subunit p65/RelA or Type-1 Transactivator T-bet Enhance Antigen Specific DNA Vaccine-Induced Immunity

Vaccines ◽  
2014 ◽  
Vol 2 (2) ◽  
pp. 196-215 ◽  
Author(s):  
Devon Shedlock ◽  
Colleen Tingey ◽  
Lavanya Mahadevan ◽  
Natalie Hutnick ◽  
Emma Reuschel ◽  
...  
Keyword(s):  
Dna Vaccine ◽  
Nf Kappa B ◽  
B Subunit ◽  
Molecular Adjuvants ◽  
Induced Immunity

scholarly journals Adjuvantic cytokine IL-33 improves the protective immunity of cocktailed DNA vaccine of ROP5 and ROP18 against toxoplasma gondii infection in mice

Parasite ◽  
2020 ◽  
Vol 27 ◽  
pp. 26 ◽  
Author(s):  
Yu-Chao Zhu ◽  
Yong He ◽  
Jian-Fa Liu ◽  
Jia Chen
Keyword(s):  
Toxoplasma Gondii ◽  
Immune Responses ◽  
Dna Vaccine ◽  
High Dose ◽  
Dna Immunization ◽  
Lethal Challenge ◽  
Molecular Adjuvant ◽  
Cell Immunity ◽  
Toxoplasma Gondii Infection ◽  
Immune Efficacy

Toxoplasma gondii is a threat for immunocompromized individuals, and no treatment is available for enhancing immunity against infection. Molecular adjuvants may improve the efficacy of DNA vaccine-induced T cell immunity. Here, we report that cocktailed DNA immunization with ROP5 and ROP18 boosted immune responses induced by a single DNA immunization with ROP5 or ROP18, but also that co-administration of molecular adjuvant IL-33 enhanced immune efficacy induced by this cocktailed DNA vaccination. These improved immune responses were characterized by higher Toxoplasma-specific IgG2a titers, Th1 responses associated with the production of IFN-γ, IL-2, IL-12, as well as cell-mediated activity with higher frequencies of CD8+ and CD4+ T cells. More importantly, this enhanced immunity has the ability to confer remarkable protection against a high dose lethal challenge of the T. gondii RH strain and thus against chronic infection with the T. gondii PRU strain. These data show that IL-33 is a promising immunoadjuvant to facilitate humoral as well as cellular immunity in a vaccine setting against T. gondii, and suggest that it should be evaluated in strategies against other apicomplexan parasites.

scholarly journals Qualitative T-Helper Responses to Multiple Viral Antigens Correlate with Vaccine-Induced Immunity to Simian/Human Immunodeficiency Virus Infection

2004 ◽  
Vol 78 (7) ◽  
pp. 3333-3342 ◽  
Author(s):  
Petra Mooij ◽  
Ivonne G. Nieuwenhuis ◽  
Christiaan J. Knoop ◽  
Robert W. Doms ◽  
Willy M. J. M. Bogers ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Critical Role ◽  
T Helper ◽  
Th2 Response ◽  
Human Immunodeficiency Virus Strain ◽  
Immunodeficiency Virus ◽  
Single Antigen ◽  
Ifn Γ ◽  
Induced Immunity ◽  
Th1 And Th2

ABSTRACT Evidence is accumulating that CD4+ T-helper (Th) responses play a critical role in facilitating effector responses which are capable of controlling and even preventing human immunodeficiency virus (HIV) infection. The present work was undertaken to determine whether immunization with multiple antigens influenced individual Th responses and increased protection relative to a single antigen. Rhesus macaques were primed with DNA and boosted (immune-stimulating complex-formulated protein) with a combination of regulatory and structural antigens (Tat-Env-Gag) or with Tat alone. Immunization with combined antigens reduced the magnitude of the responses to Tat compared to the single-antigen immunization. Interestingly, the Th immune responses to the individual antigens were noticeably different. To determine whether the qualitative differences in vaccine-induced Th responses correlated with vaccine efficacy, animals were challenged intravenously with simian/human immunodeficiency virus (strain SHIV89.6p) 2 months following the final immunization. Animals that developed combined Th1- and Th2-like responses to Gag and Th2 dominant Env-specific responses were protected from disease progression. Interestingly, one animal that was completely protected from infection had the strongest IFN-γ and interleukin-2 (IL-2) responses prior to challenge, in addition to very strong IL-4 responses to Gag and Env. In contrast, animals with only a marked vaccine-induced Tat-specific Th2 response (no IFN-γ) were not protected from infection or disease. These data support the rationale that effective HIV vaccine-induced immunity requires a combination of potent Th1- and Th2-like responses best directed to multiple antigens.

scholarly journals Integrated analysis of lncRNA, miRNA and mRNA profiles reveals potential lncRNA functions during early HIV infection

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Lianwei Ma ◽  
Hui Zhang ◽  
Yue Zhang ◽  
Hailong Li ◽  
Minghui An ◽  
...  
Keyword(s):  
Hiv Infection ◽  
Immune Activation ◽  
Expression Profiles ◽  
Critical Role ◽  
Differentially Expressed ◽  
Integrated Analysis ◽  
Target Mrnas ◽  
Immunodeficiency Virus ◽  
Mirna Sequencing ◽  
Hiv 1

Abstract Background Long noncoding RNAs (lncRNAs) can regulate gene expression in a cis-regulatory fashion or as “microRNA sponges”. However, the expression and functions of lncRNAs during early human immunodeficiency virus (HIV) infection (EHI) remain unclear. Methods 3 HAART-naive EHI patients and 3 healthy controls (HCs) were recruited in this study to perform RNA sequencing and microRNA (miRNA) sequencing. The expression profiles of lncRNAs, mRNAs and miRNAs were obtained, and the potential roles of lncRNAs were analysed based on discovering lncRNA cis-regulatory target mRNAs and constructing lncRNA–miRNA–mRNA competing endogenous RNA (ceRNA) networks. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on 175 lncRNA-associated differentially expressed (DE) mRNAs to investigate the potential functions of DE lncRNAs in ceRNA networks. Results A total of 242 lncRNAs, 1240 mRNAs and 21 mature known miRNAs were determined as differentially expressed genes in HAART-naive EHI patients compared to HCs. Among DE lncRNAs, 44 lncRNAs were predicted to overlap with 41 target mRNAs, and 107 lncRNAs might regulate their nearby DE mRNAs. Two DE lncRNAs might regulate their cis-regulatory target mRNAs BTLA and ZAP70, respectively, which were associated with immune activation. In addition, the ceRNA networks comprised 160 DE lncRNAs, 21 DE miRNAs and 175 DE mRNAs. Seventeen DE lncRNAs were predicted to regulate HIF1A and TCF7L2, which are involved in the process of HIV-1 replication. Twenty DE lncRNAs might share miRNA response elements (MREs) with FOS, FOSB and JUN, which are associated with both immune activation and HIV-1 replication. Conclusions This study revealed that lncRNAs might play a critical role in HIV-1 replication and immune activation during EHI. These novel findings are helpful for understanding of the pathogenesis of HIV infection and provide new insights into antiviral therapy.

scholarly journals Induction of Mucosal Protection against Primary, Heterologous Simian Immunodeficiency Virus by a DNA Vaccine

2002 ◽  
Vol 76 (7) ◽  
pp. 3309-3317 ◽  
Author(s):  
Deborah Heydenburg Fuller ◽  
Premeela A. Rajakumar ◽  
Lawrence A. Wilson ◽  
Anita M. Trichel ◽  
James T. Fuller ◽  
...  
Keyword(s):  
Simian Immunodeficiency Virus ◽  
Dna Vaccine ◽  
Dna Sequences ◽  
Serum Antibody ◽  
Antibody Responses ◽  
Effective Vaccine ◽  
Lymphoid Tissues ◽  
Mucosal Protection ◽  
Mucosal Transmission ◽  
Immunodeficiency Virus

ABSTRACT An effective vaccine against human immunodeficiency virus (HIV) should protect against mucosal transmission of genetically divergent isolates. As a safe alternative to live attenuated vaccines, the immunogenicity and protective efficacy of a DNA vaccine containing simian immunodeficiency virus (SIV) strain 17E-Fr (SIV/17E-Fr) gag-pol-env was analyzed in rhesus macaques. Significant levels of cytotoxic T lymphocytes (CTL), but low to undetectable serum antibody responses, were observed following multiple immunizations. SIV-specific mucosal antibodies and CTL were also detected in rectal washes and gut-associated lymphoid tissues, respectively. Vaccinated and naive control monkeys were challenged intrarectally with SIV strain DeltaB670 (SIV/DeltaB670), a primary isolate whose env is 15% dissimilar to that of the vaccine strain. Four of seven vaccinees were protected from infection as determined by the inability to identify viral RNA or DNA sequences in the peripheral blood and the absence of anamnestic antibody responses postchallenge. This is the first report of mucosal protection against a primary pathogenic, heterologous isolate of SIV by using a commercially viable vaccine approach. These results support further development of a DNA vaccine for protection against HIV.

scholarly journals Recruitment of Antigen-Presenting Cells to the Site of Inoculation and Augmentation of Human Immunodeficiency Virus Type 1 DNA Vaccine Immunogenicity by In Vivo Electroporation

2008 ◽  
Vol 82 (11) ◽  
pp. 5643-5649 ◽  
Author(s):  
Jinyan Liu ◽  
Rune Kjeken ◽  
Iacob Mathiesen ◽  
Dan H. Barouch
Keyword(s):  
Human Immunodeficiency Virus ◽  
Dna Vaccine ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Antigen Presenting Cells ◽  
In Vivo Electroporation ◽  
Immunodeficiency Virus ◽  
Antigen Presenting

ABSTRACT In vivo electroporation (EP) has been shown to augment the immunogenicity of plasmid DNA vaccines, but its mechanism of action has not been fully characterized. In this study, we show that in vivo EP augmented cellular and humoral immune responses to a human immunodeficiency virus type 1 Env DNA vaccine in mice and allowed a 10-fold reduction in vaccine dose. This enhancement was durable for over 6 months, and re-exposure to antigen resulted in anamnestic effector and central memory CD8+ T-lymphocyte responses. Interestingly, in vivo EP also recruited large mixed cellular inflammatory infiltrates to the site of inoculation. These infiltrates contained 45-fold-increased numbers of macrophages and 77-fold-increased numbers of dendritic cells as well as 2- to 6-fold-increased numbers of B and T lymphocytes compared to infiltrates following DNA vaccination alone. These data suggest that recruiting inflammatory cells, including antigen-presenting cells (APCs), to the site of antigen production substantially improves the immunogenicity of DNA vaccines. Combining in vivo EP with plasmid chemokine adjuvants that similarly recruited APCs to the injection site, however, did not result in synergy.

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