Immunization with DNA prime-subunit protein boost strategy based on influenza H9N2 virus conserved matrix protein M1 and its epitope screening.
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ABSTRACT:
SUBMITTER: Liu F
PROVIDER: S-EPMC7057951 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Chikungunya virus (CHIKV) is a reemerging mosquito-borne alphavirus that causes debilitating arthralgia in humans. Here we describe the development and testing of novel DNA replicon and protein CHIKV vaccine candidates and evaluate their abilities to induce antigen-specific immune responses against CHIKV. We also describe homologous and heterologous prime-boost immunization strategies using novel and previously developed CHIKV vaccine candidates. Immunogenicity and efficacy were studied in a mouse model of CHIKV infection and showed that the DNA replicon and protein antigen were potent vaccine candidates, particularly when used for priming and boosting, respectively. Several prime-boost immunization strategies eliciting unmatched humoral and cellular immune responses were identified. Further characterization by antibody epitope mapping revealed differences in the qualitative immune responses induced by the different vaccine candidates and immunization strategies. Most vaccine modalities resulted in complete protection against wild-type CHIKV infection; however, we did identify circumstances under which certain immunization regimens may lead to enhancement of inflammation upon challenge. These results should help guide the design of CHIKV vaccine studies and will form the basis for further preclinical and clinical evaluation of these vaccine candidates.As of today, there is no licensed vaccine to prevent CHIKV infection. In considering potential new vaccine candidates, a vaccine that could raise long-term protective immunity after a single immunization would be preferable. While humoral immunity seems to be central for protection against CHIKV infection, we do not yet fully understand the correlates of protection. Therefore, in the absence of a functional vaccine, there is a need to evaluate a number of different candidates, assessing their merits when they are used either in a single immunization or in a homologous or heterologous prime-boost modality. Here we show that while single immunization with various vaccine candidates results in potent responses, combined approaches significantly enhance responses, suggesting that such approaches need to be considered in the further development of an efficacious CHIKV vaccine.
| S-EPMC4249109 | biostudies-literature
Project description:Similar with others, our data proved that antigen-specific CD8+ T cells from mice primed with DNA and boosted by VACV were much more sensitive to antigen stimulation than those from DNA-boost. Since the mechanisms of in vivo tuning of antigen sensitivity (also termed functional avidity) is still not defined, we compared this two vaccination regimen at gene expression level. Results provide important information of which genes were selectively activated by VACV boost vaccination. For example, data shows that the expression levels of genes involved in Cancer and Wnt signaling pathways is more higher in DNA prime-VACV boost regimen that DNA prime-DNA boost vaccination. To obtain sufficient of antigen-specific cells for microarray analysis, the OVA-specific CD8+ T cells from OT-1 mice were adoptively transferred into wild type mice and then immunized by DNA and VACV vaccine encoding OVA. Four week later, mice were scarificed and antigen-specific CD8+ T cells were emriched by CD45.1-PE antibody and anti-PE MicroBeads from splenocytes.Total RNA was extracted by the RNeasy Mini Kit (QIAGEN, Germany). Followed by amplification and biotin labeling, the samples were hybridized using Illumina Total Prep RNA Amplification Kit (Ambion, USA). Mouse WG-6v2 Expression BeadChips were used for analysis of transcriptome.
2013-10-30 | E-GEOD-51849 | biostudies-arrayexpress
Project description:BackgroundTembusu virus (TMUV), a newly emerging pathogenic flavivirus, spreads rapidly between ducks, causing massive economic losses in the Chinese duck industry. Vaccination is the most effective method to prevent TMUV. Therefore, it is urgent to look for an effective vaccine strategy against TMUV. Heterologous prime-boost regimens priming with vaccines and boosting with recombinant adenovirus vaccines have been proven to be successful strategies for protecting against viruses in experimental animal models.MethodsIn this study, heterologous and homologous prime-boost strategies using an attenuated salmonella vaccine and a recombinant adenovirus vaccine expressing prM-E or the E gene of TMUV were evaluated to protect ducks against TMUV infection for the first time, including priming and boosting with the attenuated salmonella vaccine, priming and boosting with the recombinant adenovirus vaccine, and priming with the attenuated salmonella vaccine and boosting with the recombinant adenovirus vaccine. Humoral and cellular immune responses were detected and evaluated. We then challenged the ducks with TMUV at 12 days after boosting to assay for clinical symptoms, mortality, viral loads and histopathological lesions after these different strategies.ResultsCompared with the homologous prime-boost strategies, the heterologous prime-boost regimen produced higher levels of neutralizing antibodies and IgG antibodies against TMUV. Additionally, it could induce higher levels of IFN-γ than homologous prime-boost strategies in the later stage. Interestingly, the heterologous prime-boost strategy induced higher levels of IL-4 in the early stage, but the IL-4 levels gradually decreased and were even lower than those induced by the homologous prime-boost strategy in the later stage. Moreover, the heterologous prime-boost strategy could efficiently protect ducks, with low viral titres, no clinical symptoms and histopathological lesions in this experiment after challenge with TMUV, while slight clinical symptoms and histopathological lesions were observed with the homologous prime-boost strategies.ConclusionsOur results indicated that the heterologous prime-boost strategy induced higher levels of humoral and cellular immune responses and better protection against TMUV infection in ducks than the homologous prime-boost strategies, suggesting that the heterologous prime-boost strategy is an important candidate for the design of a novel vaccine strategy against TMUV.
| S-EPMC7218524 | biostudies-literature
Project description:Similar with others, our data proved that antigen-specific CD8+ T cells from mice primed with DNA and boosted by VACV were much more sensitive to antigen stimulation than those from DNA-boost. Since the mechanisms of in vivo tuning of antigen sensitivity (also termed functional avidity) is still not defined, we compared this two vaccination regimen at gene expression level. Results provide important information of which genes were selectively activated by VACV boost vaccination. For example, data shows that the expression levels of genes involved in Cancer and Wnt signaling pathways is more higher in DNA prime-VACV boost regimen that DNA prime-DNA boost vaccination.
2013-10-30 | GSE51849 | GEO
Project description:BackgroundThe objective of the present work was to assess the reactogenicity and immunogenicity of heterologous COVID-19 vaccination regimens in clinical trials and observational studies.MethodsPubMed, Cochrane Library, Embase, MedRxiv, BioRxiv databases were searched in September 29, 2021. The PRISMA instruction for systemic review was followed. Two reviewers independently selected the studies, extracted the data and assessed risk of bias. The quality of studies was evaluated using the New Castle-Ottawa and Cochrane risk of instrument. The characteristics and study outcome (e.g., adverse events, immune response, and variant of concern) were extracted.ResultsNineteen studies were included in the final data synthesis with 5 clinical trials and 14 observational studies. Heterologous vaccine administration showed a trend toward more frequent systemic reactions. However, the total reactogenicity was tolerable and manageable. Importantly, the heterologous prime-boost vaccination regimens provided higher immunogenic effect either vector/ mRNA-based vaccine or vector/ inactivated vaccine in both humoral and cellular immune response. Notably, the heterologous regimens induced the potential protection against the variant of concern, even to the Delta variant.ConclusionsThe current findings provided evidence about the higher induction of robust immunogenicity and tolerated reactogenicity of heterologous vaccination regimens (vector-based/mRNA vaccine or vector-based/inactivated vaccine). Also, this study supports the application of heterologous regimens against COVID-19 which may provide more opportunities to speed up the global vaccination campaign and maximize the capacity to control the pandemic.
| S-EPMC8767802 | biostudies-literature
Project description:The emergence of >300 serovars of Leptospira confounded the use of generalized bacterin, the whole cell lysate, as vaccines to control leptospirosis. Because of substantial genetic and geographic heterogeneity among circulating serovars, one vaccine strain per serovar cannot be efficacious against all the serovars. We have performed heterologous DNA prime-protein boost vaccination challenge studies in hamsters using in vivo expressed, leptospiral recombinase A (RecA) and flagellar hook associated protein (FliD). We prepared the monovalent recombinant protein, plasmid DNA, and DNA prime protein boost adjuvant vaccines. The whole cell bacterin served as a control. Our data show that (i) RecA and FliD have multiple immunogenic B and T-cell epitopes with highly conserved domains among most prevalent pathogenic Leptospira spp., (ii) humoral and cell mediated immune responses were induced remarkably, (iii) provides significant protection against homologous (Autumnalis strain N2) and cross-clade heterologous (Canicola strain PAI-1) challenge infection for the heterologous prime-protein boost (∼91-100%) and, the DNA vaccine (∼75-83%). Recombinant protein vaccine shows only partial protection (∼58-66%), (iv) RecA prime-protein boost vaccine shows sterilizing immunity, with heterologous protection. This RecA/FliD prime-protein boost strategy holds potential for vaccination against animal leptospirosis and for a better control of zoonotic transmission.
| S-EPMC5915591 | biostudies-literature
Project description:The present study was undertaken to determine immune response and protection efficacy of a spike (S) protein fragment containing neutralizing epitopes (4F/4R) of turkey coronavirus (TCoV) by priming with DNA vaccine and boosting with the recombinant protein from the corresponding DNA vaccine gene segment. Turkeys were vaccinated by priming with either one dose (G1-750DP) or two doses (G3-750DDP) of 750?g DNA vaccine expressing 4F/4R S fragment and boosting with one dose of 200?g 4F/4R S fragment. One dose of 100?g DNA vaccine mixed with polyethyleneimine (PEI) and sodium hyaluronate (HA) followed by one dose of 750?g DNA vaccine and one dose of 200?g 4F/4R S fragment were given to the turkeys in group G2-100DPH. After infectious challenge by TCoV, clinical signs and TCoV detected by immunofluorescence antibody (IFA) assay were observed in less number of turkeys in vaccination groups than that in challenge control groups. TCoV viral RNA loads measured by quantitative real-time reverse transcription-PCR were lower in vaccinated turkeys than those in challenge control turkeys. The turkeys in G3-750DDP produced the highest level of TCoV S protein-specific antibody and virus neutralization (VN) titer. Comparing to the turkeys in G1-750DP, significantly less TCoV were detected by IFA in the turkeys in G2-100DPH receiving an extra dose of 100?g DNA mixed with PEI and HA. The results indicated that DNA-prime protein-boost DNA vaccination regimen targeting TCoV S fragment encompassing neutralizing epitopes induced humoral immune response and partially protected turkeys against infectious challenge by TCoV.
| S-EPMC7112546 | biostudies-literature
Project description:SARS-CoV-2 vaccines are advancing into human clinical trials, with emphasis on eliciting high titres of neutralising antibodies against the viral spike (S). However, the merits of broadly targeting S versus focusing antibody onto the smaller receptor binding domain (RBD) are unclear. Here we assess prototypic S and RBD subunit vaccines in homologous or heterologous prime-boost regimens in mice and non-human primates. We find S is highly immunogenic in mice, while the comparatively poor immunogenicity of RBD is associated with limiting germinal centre and T follicular helper cell activity. Boosting S-primed mice with either S or RBD significantly augments neutralising titres, with RBD-focussing driving moderate improvement in serum neutralisation. In contrast, both S and RBD vaccines are comparably immunogenic in macaques, eliciting serological neutralising activity that generally exceed levels in convalescent humans. These studies confirm recombinant S proteins as promising vaccine candidates and highlight multiple pathways to achieving potent serological neutralisation.
| S-EPMC7930087 | biostudies-literature
Project description:Alpha fetoprotein (AFP) is an oncofetal antigen over-expressed by many hepatocellular cancers (HCC). We previously demonstrated that HLA-A2-restricted epitopes derived from AFP are immunogenic in vitro and in vivo despite high circulating levels of this oncofetal antigen. In order to test a more broadly applicable, HLA-unrestricted, inexpensive, cell-free vaccine platform capable of activating tumor antigen-specific CD8+ and CD4+ T cells, we tested full length AFP in a plasmid DNA construct in combination with an AFP-expressing replication-deficient adenovirus (AdV) in a prime-boost vaccine strategy.HCC patients who had an AFP+ tumor and previous treatment for HCC were screened and two patients received vaccination with three plasmid DNA injections followed by a single AdV injection, all delivered intramuscularly (i.m.).The vaccine was well tolerated and safe. Both patients showed immunologic evidence of immunization. The first patient had a weak AFP-specific T cell response, a strong AdV-specific cellular response and recurred with an AFP-expressing HCC at nine months. The second patient developed a strong AFP-specific CD8+ and CD4+ cellular response and an AdV neutralizing antibody response, and recurred at 18 months without an increase in serum AFP.The AFP DNA prime-AdV boost vaccine was safe and immunogenic. Circulating anti-AdV neutralizing antibodies at baseline did not prohibit the development of AFP-specific cellular immunity. The patient who developed CD8+ and CD4+ AFP-specific T cell immunity had more favorable progression-free survival. The observations with these two patients support development of this vaccine strategy in a larger clinical trial.ClinicalTrials.gov: NCT00093548.
| S-EPMC4021640 | biostudies-literature
Project description:Therapeutic cancer vaccines aim to induce an effective immune response against cancer, and the effectiveness of these vaccines is influenced by the choice of immunogen, vaccine type, and immunization strategy. Although treatment with cancer vaccines can improve tumor burden and survival, in most animal studies, it is challenging to achieve a complete response against tumor growth and recurrence, without the use of other therapies in combination. Here, we present a novel approach where dual antigens (survivin and MUC1) are co-targeted using three DNA vaccines, followed by a single booster of a recombinant modified vaccinia Ankara (MVA) vaccine. This heterologous vaccination strategy induced higher levels of interferon (IFN)-γ-secretion and stronger antigen-specific T-cell responses than those induced individually by the DNA vaccines and the MVA vaccine in mice. This strategy also increased the number of active tumor-infiltrating T cells that efficiently inhibit tumor growth in tumor-bearing mice. Heterologous DNA prime-MVA boost immunization was capable of inducing a robust antigen-specific immune-memory, as seen from the resistance to subsequent survivin- and MUC1-expressing tumors. Moreover, the therapeutic effects of DNA prime-MVA boost and DNA prime-adenovirus boost strategies were compared. DNA prime-MVA boost immunization performed better, as indicated by the T effector ratio and the induction of Th1 immunity. This study provides the basis for the use of heterologous DNA prime-MVA boost vaccination regime targeting two antigens simultaneously as a promising immunotherapeutic strategy against cancer.
| S-EPMC7657584 | biostudies-literature