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At least 19 recordsLinked to original sources
PubMed2026

Comparative Genomics-Guided Epitope Prioritization and in Silico Design of a Multi-Epitope DNA Vaccine Candidate Against Megalocytivirus pagrus 1.

Megalocytivirus pagrus 1 infection is a World Organisation for Animal Health-listed aquatic animal disease caused by a virus species comprising the RSIV, ISKNV, and TRBIV genogroups. Here, we integrated comparative genomics and immunoinformatics to prioritize a multi-epitope protein construct, pMEV, and to design a DNA vaccine candidate encoding it, with emphasis on RSIV-type infection relevant to rock bream aquaculture. Analysis of 61 complete genomes identified 28 core gene clusters, from which myristoylated membrane protein (MMP) and major capsid protein (MCP) were prioritized as source antigens for epitope screening. Four cytotoxic T-cell, five helper T-cell, and five linear B-cell epitope candidates were selected based on sequence-based screening and exploratory peptide-MHC docking. The selected epitopes were assembled with rock bream beta-defensin-3, PADRE, and peptide linkers to generate the 283-aa pMEV construct. Sequence-based physicochemical analyses indicated properties relevant to subsequent structural and expression-based evaluation, while computationally refined structural modeling identified nine putative conformational B-cell epitope regions. TLR3 docking, normal mode analysis, and a 200-ns molecular dynamics simulation characterized the structural behavior of the selected computational complex without inferring receptor activation. C-ImmSim further generated model-dependent generic humoral and helper T-cell-associated response patterns within a mammalian-based simulation framework. Finally, the pMEV coding sequence was codon-optimized and incorporated into an in silico pcDNA3.1(+)-based DNA vaccine design. Collectively, this study provides a comparative genomics-guided framework for prioritizing an experimentally testable multi-epitope DNA vaccine candidate against M. pagrus 1, while construct expression, immunogenicity, and protective efficacy remain to be evaluated experimentally.

Animals↗
PubMed2026

Synthetic long peptide and DNA personalized cancer vaccines induce robust neoantigen-specific T cell responses in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is unresponsive to standard immunotherapies despite harboring cancer neoantigens capable of eliciting T cell responses. We completed two phase 1 clinical trials (NCT03956056 and NCT03122106) evaluating safety and immunogenicity of synthetic long peptide (SLP) and DNA personalized cancer vaccines (PCVs). PCVs were administered after resection and adjuvant chemotherapy. Tumor/normal whole-exome sequencing, RNA sequencing, and pVACtools were used to identify and prioritize candidate PCV neoantigens. PCVs were well tolerated without any grade ≥3 adverse events. Neoantigen-specific responses were demonstrated by interferon-γ enzyme-linked immunospot and intracellular cytokine staining. Expanded T cell receptor clonotypes were sequenced and transduced into autologous peripheral blood mononuclear cells to confirm neoantigen specificity. When compared with a contemporaneous institutional propensity-matched cohort, PCV patients demonstrated a trend toward prolonged median overall survival (4.4 versus 3.5 years, log-rank P = 0.23). Overall, PDAC PCVs are safe and feasible and elicit polyclonal T cell responses, linking prioritized cancer neoantigens to functional antitumor immunity.

Humans↗
PubMedDate not supplied

[Analysis of cultures infected by vaccinal strains of viruses for detecting in them the integrated genome of these viruses (author's transl)].

White mice of 10-12 g were immunized with one of the three virus vaccines (vaccines against poliomyelitis, measles, smallpox) at various intervals. Poliovirus type II and measles virus, Edmonston strain, were labeled in tissue culture with 3H-uridine (30/uCi/ml). Smallpox virus (rabbit strain) was labeled with 3H-thymidine (30/uCi per ml) also in tissue culture. After purification and concentration of labeled poliomyelitis and measles viruses, viral RNA was isolated by double extraction with phenol, and precipitation with alcohol to which a yeast RNA-carrier was added. Isolation of 3H-thymidine-labeled viral RNA from smallpox virus was carried out by the same method with the addition of SDS to the final concentration of 1%. From the brain and lung cells of the vaccinated animals DNA was extracted by the kinetic reassociation method and hybridized with labeled viral nucleic acids. The formation of a hybrid with DNA-containing vaccine virus was controlled by chromatography in hydroxylapatite. No integration of viral and cell nucleic acids was demonstrated in our experiments, however, it cannot be ruled out completely, because this method does not detect homologous sequences if they occur in a small number of cells tested.

Animals↗
PubMed2026

Development of a recombinant goose parvovirus VP2 neutralizing epitope-containing region vaccine adjuvanted with IL-2 and FliC for enhanced immune responses and protection against challenge.

Gosling plague (GP), caused by goose parvovirus (GPV), is a highly contagious and fatal viral disease. Vaccination is essential for disease prevention; however, conventional attenuated and inactivated vaccines have several limitations. Genetically engineered vaccines based on defined antigenic regions represent a promising alternative strategy. This study aimed to identify neutralizing epitope-containing regions within the GPV VP2 protein and develop effective recombinant vaccines. The GPV VP2 protein was divided into 11 overlapping fragments, and the anchored periplasmic expression (APEx) bacterial display system combined with flow cytometry (FCM) was used for antigenic region screening. GPV VP2-specific single-domain antibodies (VHHs) were further applied to identify neutralizing epitope-containing regions. Six neutralizing epitope-containing regions were identified and linked together to construct the VP2M recombinant antigen. The VP, VP2M, interleukin-2 (IL-2), and flagellin (FliC) genes were inserted into prokaryotic and eukaryotic expression vectors to generate protein and DNA vaccines. Three-day-old goslings were randomly assigned into 15 experimental groups for immunization. Immune responses were evaluated by measuring anti-GPV antibody levels, IgG, IgM, and IgA production, IFN-γ levels, immune-related gene expression, splenocyte proliferation, neutralizing activity, and protective efficacy against GPV challenge. The results showed that vaccines containing neutralizing epitope-containing regions induced stronger immune responses than control vaccines. Vaccinated groups exhibited increased anti-GPV antibody levels, IgG, IgM, IgA production, IFN-γ levels, immune-related gene expression, and splenocyte proliferation. Following GPV challenge, VP2M-based vaccines significantly reduced viral genome copies in the bursa of Fabricius, spleen, thymus, and intestinal tissues, accompanied by decreased histopathological lesions based on semi-quantitative scoring. Furthermore, the protective efficacy exceeded 50% in vaccines without adjuvants and reached 90% in groups containing combined IL-2 and FliC adjuvants. In conclusion, this study identifies novel neutralizing epitope-containing regions within GPV VP2 and provides a potential strategy for developing safe and effective recombinant vaccines against GP infection.

GP↗
PubMed1979

Antibody and cell-mediated immunity to a DNA free herpes simplex subunit vaccine.

The immunogenicity of a DNA free herpes simplex subunit vaccine was evaluated in chimpanzees and rabbits. The results clearly demonstrate that 1 injection of 3 micrograms/kg elicited antibodies as well as cell-mediated immunity in all the animals studied. These antibodies persisted for at least 6 months. Furthermore the vaccine also protected 50% of the animals against an experimental infection and reduced the rate of latent infection in nervous sensory ganglia.

Animals↗
PubMed1979

Intestinal immunity and vaccine development: a WHO memorandum.

As part of the research component of the WHO Diarrhoeal Diseases Control Programme, a Scientific Working Group met in August 1978 to review recent advances in knowledge of intestinal immunity, the application of genetic techniques in enteric vaccine development, the status of currently available immunizing agents against cholera, typhoid fever, and Shigella dysentery, and the prospects for the development of new or improved vaccines against the well known and newly recognized agents such as rotavirus and enterotoxigenic Escherichia coli. In each of these areas, the Group made specific recommendations for further research that should be considered for support under the WHO research programme in the field of diarrhoeal diseases.

Animals↗
PubMedDate not supplied

Comparative studies of different strains of BCG vaccine in mice: T-cell dependent immune responses.

Three tests have been selected to demonstrate the close relationship between the innate immunogenicity and immunopotentiating capacity of different strains of BCG vaccines grown under the same conditions. The five strains of BCG which have been most extensively studied were PASTEUR, PHIPPS, TICE, CONNAUGHT and GLAXO. The first four are alike, they have similar growth characteristics and closely resemble each other, in immunological properties-lymphoproliferative response in vivo and T-cell potentiating effect-PASTEUR BCG being the strongest. GLAXO strain is different in these respects and is shown to have atypical properties.

Animals↗
PubMed1979

Effect of BCG on cytostatic activity of peritoneal macrophages from normal and tumor-bearing rats.

In tumor-bearing rats inoculated intramuscularly with 5 x 10(4) SLC cells, the cytostatic activity of peritoneal macrophages was elevated in the early stage (7 days after transplantation) and decreased in the advanced stage (21 days after transplantation). When BCG was intraperitoneally administered into normal and tumor-bearing rats, peritoneal macrophages showed higher cytostatic activity than the untreated macrophages. This elevated cytostatic activity of the marcophages obtained from BCG-treated tumor-bearing rats was maintained even at an advanced stage.

Animals↗
PubMed2026

Therapeutic melanoma vaccines: Platforms, neoantigen strategies, and emerging combination immunotherapies.

Melanoma has emerged as a major focus of cancer immunotherapy research because of its highly immunogenic nature and responsiveness to immune-based treatments. Therapeutic melanoma vaccines are designed to stimulate tumor-specific immune responses through the delivery of Tumor-Associated Antigens (TAAs), Tumor-Specific Antigens (TSAs), and personalized neoantigens. This narrative review provides an overview of current melanoma vaccine strategies, including peptide-based vaccines, dendritic cell vaccines, nucleic acid-based platforms such as mRNA, DNA, and viral vector vaccines. Recent advances in vaccine engineering and tumor genomics have accelerated the development of personalized neoantigen vaccines capable of targeting mutations unique to individual tumors. In parallel, Artificial Intelligence (AI) and Machine Learning (ML) are increasingly being incorporated into neoantigen identification pipelines to improve epitope prediction and optimize vaccine design. Combination strategies involving Immune Checkpoint Inhibitors (ICIs), particularly anti-PD-1 and anti-CTLA-4 therapies, have further enhanced interest in melanoma vaccines by helping overcome tumor-induced immune suppression and augment T-cell activation. In addition to reviewing vaccine mechanisms and emerging technologies, this manuscript examines the evolving clinical trial landscape through analysis of melanoma vaccine studies registered on ClinicalTrials.gov. Although many studies have reported encouraging safety and immunogenicity findings, challenges related to tumor heterogeneity, immune evasion, biomarker selection, and manufacturing complexity continue to limit widespread clinical implementation. Ongoing advances in computational immunology, biomaterial engineering, and precision oncology are expected to further refine melanoma vaccine development and improve therapeutic efficacy. Collectively, these innovations may help establish melanoma vaccines as an increasingly important component of future personalized cancer immunotherapy strategies.

DNA vaccines↗
PubMed1979

Comparative studies on Marek's disease virus and herpesvirus of turkey DNAs.

DNA of Marek's disease virus (MDV) was compared to that of herpes virus of turkey (HVT). Centrifugation of the two virus DNAs in neutral glycerol and CsCl density gradients showed that the MDV genome was slightly larger than that of HVT and that the buoyant density (1.705 g/ml) of MDV DNA in CsCl gradients was slightly lower than that (1.707 g/ml) of HVT DNA. MDV and HVT DNAs were digested with either EcoRI or HindIII restriction endonuclease and analysed by 0.5% agarose gel electrophoresis. The cleavage patterns of HindIII or EcoRI DNA digests of two strains of these two viruses showed general similarities between the strains, but not between MDV and HVT. However, a few fragments of EcoRI or HindIII digests of MDV DNA co-migrated with those of HVT DNA. DNA-DNA reassociation kinetics and DNA-RNA hybridization between the two viruses indicated that MDV and HVT DNAs share detectable homology, although it is less than 5%. The DNA of a HVT variant, which has lost the ability to protect chickens from Marek's disease, appeared similar to DNA of the vaccine strain in the size buoyant density and in its restriction endonuclease cleavage pattern.

Animals↗
PubMed2026

Emerging techniques of CRISPR/Cas system in antiviral therapy and diagnostics: Applications, limitations, and translational perspectives.

The CRISPR/Cas (clustered regularly interspaced short palindromic repeats) system is a versatile technology for developing antiviral medicines and editing viral genomes in both diagnostics and vaccine synthesis. Emerging insights into class 2 effectors, such as Cas9, Cas12, and Cas13, which target viral DNA and RNA, have revolutionized vaccines against viruses such as HIV, HPV, HBV, and EBV. Innovative diagnostic techniques such as SHERLOCK, DETECTR, and FELUDA have demonstrated system's diversity and accuracy in detecting the virus markers, supporting clinical decision-making, indicating adaptability and precision of CRISPR. This review critically evaluates CRISPR's role in RNA editing, emphasizing its importance for functional genomics and development of recombinant vaccines. Translational challenges are critically discussed, including off-target effects, delivery limitations, and ethical issues, for which unique approaches such as high-fidelity Cas variants, non-viral delivery systems, and bioethical frameworks are evaluated to address these limitations. This review also covers other social implications, such as accessibility and biosecurity risks, associated with CRISPR technologies Collectively, these advances underscore the transformative potential of CRISPR technologies in shaping next-generation antiviral diagnostics and therapeutics.

CRISPR-Cas Systems↗
PubMed2005

Characterization of the genetic lineages responsible for pneumococcal invasive disease in Portugal.

The availability of a conjugate vaccine has the potential to reduce the disease burden of pneumococci and to alter the serotype frequency in the disease-causing population through immunoselection. These changes will probably be reflected in the distributions of individual genetic lineages within the population. We present a characterization of a collection of recent (1999 to 2002) invasive isolates from Portugal (n = 465) by macrorestriction profiling with pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing. During this time, serotypes 14, 1, 3, 4, 8, 9V, 23F, 7F, 19A, and 12B were the 10 most prevalent overall by decreasing rank order. By combining the PFGE data with the sequence types (STs) of 104 isolates, we were able to identify the genetic lineages of the majority of the isolates. We found 66 STs, including 20 novel STs, corresponding to 47 different lineages by e-BURST analysis. We found in our collection a number of previously identified internationally disseminated lineages, especially among macrolide-resistant and penicillin-resistant isolates, and these accounted for most of the isolates. Most of the major lineages (17 of 25) were identified in all years of the study, suggesting that the pneumococcal population associated with invasive disease was stable. This study provides a characterization of the pneumococcal population associated with invasive disease that will be useful for detecting potential selective effects of the novel conjugate vaccine.

Alleles↗
PubMed1979

Sister chromatid exchange in peripheral lymphocytes of subjects vaccinated against measles.

The SCE frequency was studied in cultures of peripheral lymphocytes from three subjects before and after vaccination against measles. The immunological vaccination reactions were monitored by antibody titration and by measurement of DNA synthesis in peripheral lymphocytes. In two of the subjects, on the 14th day after vaccination, there was a marked decrease of the SCE frequency coinciding with common clinical vaccination reactions and an increase of DNA synthesis in the peripheral lymphocytes. The increase of antibody titers started on the 17th day. One month later, when the immunological reactions had subsided, the SCE frequency was increased by 25% over the prevaccination level. Third subject displayed a delayed vaccination response due to a simultaneous influenza infection. This subject showed a 50% increase in the SCE frequency on the 14th day as well as 6 weeks after vaccination. These results suggest that significant changes in the SCE frequency may be related to immunological vaccination reactions.

Adult↗
PubMed1977

Sequential examination of lymphocyte proliferative capacity in patients with malignant melanoma receiving BCG immunotherapy.

A series of 42 patients with malignant melanoma treated with BCG adjuvant immunotherapy were studied for sequential changes in cellular immune reactivity to non-specific mitogens. Lymphocyte preparations were made monthly and stored in a viable condition in liquid nitrogen. After 6 months of treatment, all lymphocyte samples from an individual were recovered and tested for DNA synthesis after stimulation with PHA, PWM, Con A, PPD and MLC. The responses to the mitogens in the blastogenesis test were stable during the course of therapy. The MLC response did not increase significantly in patients treated with tumor-cell vaccines, and declined sharply in the six patients who subsequently relapsed and died. The in vitro PPD response increased 1 to 3 months after initiation of BCG in patients who were initially unresponsive to PPD in vitro. However, PPD-positive patients did not show any significant alteration of the PPD response. The PPD response did increase less sharply in patients whose disease eventually recurred than in those who remained without evidence of clinical disease. BCG therapy does not appear to correct lymphocyte proliferative defects in melanoma patients. Of the assays employed, the MLC and PPD tests appear to be the most useful as monitors of clinical status and response to therapy.

BCG Vaccine↗
PubMed1975

Screen for type-C ribonucleic acid viruses in vaccines using the ribonucleic acid-dependent deoxyribonucleic acid polymerase assay.

The ribonucleic acid-dependent deoxyribonucleic acid polymerase assay was used to detect type-C viruses in live virus vaccines. Conditions were first established to maximize the sensitivity of the assay. Vaccines tested included live poliomyelitis, rubella, measles, mumps, and yellow fever. Only yellow fever and measles vaccines known to have been produced in avian leukosis-contaminated cells showed evidence of type-C viruses using the assay. The result of the survey show that the assay has direct practical application to the problem of detecting latent agents in biological products intended for human use.

Avian Sarcoma Viruses↗