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  • 1
    In: Infectious Agents and Cancer, Springer Science and Business Media LLC, Vol. 17, No. 1 ( 2022-12)
    Abstract: Both SARS-CoV-2 mRNA-based vaccines [BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna)] have shown high efficacy, with very modest side effects in limiting transmission of SARS-CoV-2 and in preventing the severe COVID-19 disease, characterized by a worrying high occupation of intensive care units (ICU), high frequency of intubation and ultimately high mortality rate. At the INT, in Naples, only the BNT162b2/Pfizer vaccine has been administered to cancer patients and healthcare professionals aged 16 and over. In the present study, the antibody response levels and their decline were monitored in an interval of 6–9 months after vaccine administration in the two different cohorts of workers of the INT – IRCCS "Fondazione Pascale" Cancer Center (Naples, Italy): the group of individuals previously infected with SARS-CoV-2 and vaccinated with a single dose; and that of individuals negative for previous exposure to SARS-CoV-2 vaccinated with two doses 21 days apart. Methods Specific anti-RBD (receptor-binding domain) titers against trimeric spike glycoprotein (S) of SARS-CoV-2 by Roche Elecsys Anti-SARS-CoV-2 S ECLIA immunoassay were determined in serum samples of 27 healthcare workers with a previously documented history of SARS-CoV-2 infection and 123 healthcare workers without, during antibody titers’ monitoring. Moreover, geometric mean titers (GMT) and relative fold changes (FC) were calculated. Results Bimodal titer decline was observed in both previously infected and uninfected SARS-CoV-2 subjects. A first rapid decline was followed by a progressive slow decline in the 6/9 month-period before the further vaccine boost. The trend was explained by 2 different mathematical models, exponential and power function, the latter revealing as predictive of antibody titer decline either in infected or in not previously infected ones. The value of the prolonged lower vaccine titer was about 1 log below in the 6/9-month interval after the single dose for previously infected individuals with SARS-CoV-2 and the two doses for those not previously infected. The titer change, after the boost dose administration, on the other hand, was ≥ 1.5 FC higher than the titers at the 6/9-month time-points in both cohorts. A similar quantitative immune titer was observed in both cohorts 8 days after the last boost dose. The subsequent immunoresponse trend remains to be verified. Discussion The results show that a very rapid first decline, from the highest antibody peak, was followed by a very slow decline which ensured immune protection lasting more than 6 months. The apparent absence of adverse effects of the rapid decline on the vaccine's immune protective role has been related to a large majority of low avidity antibodies induced by current vaccines. High avidity antibodies with prolonged anti-transmission efficacy show a longer half-life and are lost over a longer interval period. The cellular immunity, capable of preventing severe clinical diseases, lasts much longer. The unbalanced dual activity (cellular vs humoral) while effective in limiting ICU pressure and overall mortality, does not protect against transmission of SARS-CoV-2, resulting in high circulation of the virus among unvaccinated subjects, including the younger population, and the continuous production of variants characterized by changes in transmissibility and pathogenicity. The high mutation rate, peculiar to the RNA virus, can however lead to a dual opposite results: selection of defective and less efficient viruses up to extinction; risk of more efficiently transmitted variants as the current omicron pandemic. Conclusions In conclusion the current bimodal antibody-titer decline, following BNT162b2 mRNA anti-SARS-CoV-2 vaccination, needs a further extended analysis to verify the protective borderline levels of immunity and the optimal administration schedule of vaccine boosters. Our current results can contribute to such goal, besides a direct comparison of other FDA-approved and candidate vaccines.
    Type of Medium: Online Resource
    ISSN: 1750-9378
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2251117-9
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  • 2
    In: Cancers, MDPI AG, Vol. 14, No. 21 ( 2022-10-26), p. 5257-
    Abstract: Human oncoviruses are able to subvert telomerase function in cancer cells through multiple strategies. The activity of the catalytic subunit of telomerase (TERT) is universally enhanced in virus-related cancers. Viral oncoproteins, such as high-risk human papillomavirus (HPV) E6, Epstein–Barr virus (EBV) LMP1, Kaposi’s sarcoma-associated herpesvirus (HHV-8) LANA, hepatitis B virus (HBV) HBVx, hepatitis C virus (HCV) core protein and human T-cell leukemia virus-1 (HTLV-1) Tax protein, interact with regulatory elements in the infected cells and contribute to the transcriptional activation of TERT gene. Specifically, viral oncoproteins have been shown to bind TERT promoter, to induce post-transcriptional alterations of TERT mRNA and to cause epigenetic modifications, which have important effects on the regulation of telomeric and extra-telomeric functions of the telomerase. Other viruses, such as herpesviruses, operate by integrating their genomes within the telomeres or by inducing alternative lengthening of telomeres (ALT) in non-ALT cells. In this review, we recapitulate on recent findings on virus–telomerase/telomeres interplay and the importance of TERT-related oncogenic pathways activated by cancer-causing viruses.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2527080-1
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  • 3
    In: Cancers, MDPI AG, Vol. 12, No. 4 ( 2020-04-23), p. 1049-
    Abstract: Nanoparticles represent a potent antigen presentation and delivery system to elicit an optimal immune response by effector cells targeting tumor-associated antigens expressed by cancer cells. Many types of nanoparticles have been developed, such as polymeric complexes, liposomes, micelles and protein-based structures such as virus like particles. All of them show promising results for immunotherapy approaches. In particular, the immunogenicity of peptide-based cancer vaccines can be significantly potentiated by nanoparticles. Indeed, nanoparticles are able to enhance the targeting of antigen-presenting cells (APCs) and trigger cytokine production for optimal T cell response. The present review summarizes the categories of nanoparticles and peptide cancer vaccines which are currently under pre-clinical evaluation.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2527080-1
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  • 4
    Online Resource
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    Informa UK Limited ; 2022
    In:  Expert Opinion on Therapeutic Targets Vol. 26, No. 9 ( 2022-09-02), p. 767-780
    In: Expert Opinion on Therapeutic Targets, Informa UK Limited, Vol. 26, No. 9 ( 2022-09-02), p. 767-780
    Type of Medium: Online Resource
    ISSN: 1472-8222 , 1744-7631
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 2022
    detail.hit.zdb_id: 2028202-3
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  • 5
    In: Journal of Translational Medicine, Springer Science and Business Media LLC, Vol. 21, No. 1 ( 2023-02-14)
    Abstract: The infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has unpredictable manifestations of coronavirus disease (COVID-19) and variable clinical course with some patients being asymptomatic whereas others experiencing severe respiratory distress, or even death. We aimed to evaluate the immunoglobulin G (IgG) response towards linear peptides on a peptide array containing sequences from SARS-CoV-2, Middle East respiratory syndrome-related coronavirus (MERS) and common-cold coronaviruses 229E, OC43, NL63 and HKU1 antigens, in order to identify immunological indicators of disease outcome in SARS-CoV-2 infected patients. Methods We included in the study 79 subjects, comprising 19 pediatric and 30 adult SARS-CoV-2 infected patients with increasing disease severity, from mild to critical illness, and 30 uninfected subjects who were vaccinated with one dose of SARS-CoV-2 spike mRNA BNT162b2 vaccine. Serum samples were analyzed by a peptide microarray containing 5828 overlapping 15-mer synthetic peptides corresponding to the full SARS-CoV-2 proteome and selected linear epitopes of spike (S), envelope (E) and membrane (M) glycoproteins as well as nucleoprotein (N) of MERS, SARS and coronaviruses 229E, OC43, NL63 and HKU1 (isolates 1, 2 and 5). Results All patients exhibited high IgG reactivity against the central region and C-terminus peptides of both SARS-CoV-2 N and S proteins. Setting the threshold value for serum reactivity above 25,000 units, 100% and 81% of patients with severe disease, 36% and 29% of subjects with mild symptoms, and 8% and 17% of children younger than 8-years reacted against N and S proteins, respectively. Overall, the total number of peptides in the SARS-CoV-2 proteome targeted by serum samples was much higher in children compared to adults. Notably, we revealed a differential antibody response to SARS-CoV-2 peptides of M protein between adults, mainly reacting against the C-terminus epitopes, and children, who were highly responsive to the N-terminus of M protein. In addition, IgG signals against NS7B, NS8 and ORF10 peptides were found elevated mainly among adults with mild (63%) symptoms. Antibodies towards S and N proteins of other coronaviruses (MERS, 229E, OC43, NL63 and HKU1) were detected in all groups without a significant correlation with SARS-CoV-2 antibody levels. Conclusions Overall, our results showed that antibodies elicited by specific linear epitopes of SARS-CoV-2 proteome are age dependent and related to COVID-19 clinical severity. Cross-reaction of antibodies to epitopes of other human coronaviruses was evident in all patients with distinct profiles between children and adult patients. Several SARS-CoV-2 peptides identified in this study are of particular interest for the development of vaccines and diagnostic tests to predict the clinical outcome of SARS-CoV-2 infection.
    Type of Medium: Online Resource
    ISSN: 1479-5876
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2118570-0
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  • 6
    In: Cancers, MDPI AG, Vol. 10, No. 7 ( 2018-06-22), p. 213-
    Abstract: Viral oncogenesis is a multistep process largely depending on the complex interplay between viruses and host factors. The oncoviruses are capable of subverting the cell signaling machinery and metabolic pathways and exploit them for infection, replication, and persistence. Several viral oncoproteins are able to functionally inactivate the tumor suppressor p53, causing deregulated expression of many genes orchestrated by p53, such as those involved in apoptosis, DNA stability, and cell proliferation. The Epstein–Barr virus (EBV) BZLF1, the high-risk human papillomavirus (HPV) E6, and the hepatitis C virus (HCV) NS5 proteins have shown to directly bind to and degrade p53. The hepatitis B virus (HBV) HBx and the human T cell lymphotropic virus-1 (HTLV-1) Tax proteins inhibit p53 activity through the modulation of p300/CBP nuclear factors, while the Kaposi’s sarcoma herpesvirus (HHV8) LANA, vIRF-1 and vIRF-3 proteins have been shown to destabilize the oncosuppressor, causing a decrease in its levels in the infected cells. The large T antigen of the Merkel cell polyomavirus (MCPyV) does not bind to p53 but significantly reduces p53-dependent transcription. This review describes the main molecular mechanisms involved in the interaction between viral oncoproteins and p53-related pathways as well as in the development of therapeutic strategies targeting such interactions.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    Language: English
    Publisher: MDPI AG
    Publication Date: 2018
    detail.hit.zdb_id: 2527080-1
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  • 7
    In: Molecular Aspects of Medicine, Elsevier BV, Vol. 92 ( 2023-08), p. 101192-
    Type of Medium: Online Resource
    ISSN: 0098-2997
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2023
    detail.hit.zdb_id: 2008203-4
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  • 8
    In: Molecules, MDPI AG, Vol. 25, No. 12 ( 2020-06-19), p. 2850-
    Abstract: Antimicrobial peptides (AMPs), or host defense peptides, are small cationic or amphipathic molecules produced by prokaryotic and eukaryotic organisms that play a key role in the innate immune defense against viruses, bacteria and fungi. AMPs have either antimicrobial or anticancer activities. Indeed, cationic AMPs are able to disrupt microbial cell membranes by interacting with negatively charged phospholipids. Moreover, several peptides are capable to trigger cytotoxicity of human cancer cells by binding to negatively charged phosphatidylserine moieties which are selectively exposed on the outer surface of cancer cell plasma membranes. In addition, some AMPs, such as LTX-315, have shown to induce release of tumor antigens and potent damage associated molecular patterns by causing alterations in the intracellular organelles of cancer cells. Given the recognized medical need of novel anticancer drugs, AMPs could represent a potential source of effective therapeutic agents, either alone or in combination with other small molecules, in oncology. In this review we summarize and describe the properties and the mode of action of AMPs as well as the strategies to increase their selectivity toward specific cancer cells.
    Type of Medium: Online Resource
    ISSN: 1420-3049
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2008644-1
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  • 9
    In: Vaccines, MDPI AG, Vol. 10, No. 2 ( 2022-02-02), p. 227-
    Abstract: Virus-like particles (VLPs) are self-assembled viral protein complexes that mimic the native virus structure without being infectious. VLPs, similarly to wild type viruses, are able to efficiently target and activate dendritic cells (DCs) triggering the B and T cell immunities. Therefore, VLPs hold great promise for the development of effective and affordable vaccines in infectious diseases and cancers. Vaccine formulations based on VLPs, compared to other nanoparticles, have the advantage of incorporating multiple antigens derived from different proteins. Moreover, such antigens can be functionalized by chemical modifications without affecting the structural conformation or the antigenicity. This review summarizes the current status of preventive and therapeutic VLP-based vaccines developed against human oncoviruses as well as cancers.
    Type of Medium: Online Resource
    ISSN: 2076-393X
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2703319-3
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  • 10
    In: Current Medicinal Chemistry, Bentham Science Publishers Ltd., Vol. 29, No. 15 ( 2022-05), p. 2736-2747
    Abstract: Chronic infection with hepatitis C virus (HCV) is among the major causes of hepatic fibrosis, cirrhosis, as well as hepatocellular carcinoma (HCC), and it is associated with a significant risk of developing lymphoproliferative disorders. The rate of clinical disease progression is variable depending on multiple host and viral factors, including immune response. Methods: To perform a comprehensive epitope mapping of anti-HCV antibodies in patients suffering from HCV-related liver or lymphoproliferative diseases, we analyzed clinical samples on a peptide microarray platform made of 5952 overlapping 15-mer synthetic peptides derived from the whole HCV proteome. We evaluated the antibody profile of 71 HCV-positive patients diagnosed with HCC, mixed cryoglobulinemia (MC), and HCV chronic infection. Antibody reactivity against virus peptides was detected in all HCVpositive patients. Importantly, the signal amplitude varied significantly within and between diverse patient groups. Results: Antibody reactivity against C peptides were found generally low in HCV chronically infected asymptomatic subjects and increasingly high in HCC and MC patients. Moreover, we found a statistically significant higher IgG response in HCC and MC patients against specific domains of HCV C, E2, NS3, NS4A, NS4B, NS5A, and p7 compared to HCV-positive subjects. Conclusion: In conclusion, our data suggest that immune response against specific HCV protein domains may represent useful biomarkers of disease progression among HCVpositive patients and suggest that peptide microarrays are good tools for the screening of immunotherapy targets in preclinical HCV research.
    Type of Medium: Online Resource
    ISSN: 0929-8673
    Language: English
    Publisher: Bentham Science Publishers Ltd.
    Publication Date: 2022
    SSG: 15,3
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