Perspective Technologies of Vaccination : Do We Still Need Old Vaccines?

Funding Information: Acknowledgments: The authors gratefully acknowledge the Department of Science and Technology fund and grant #U98346 from the National Research Foundation administered South African Research Chair Initiative for Vector-borne and Zoonotic Pathogens Research, RFBR grant #20-04-01034, and Latvian Science Council grants #LZP-2020/2-0376 and #LZP-2021/1-0484 for their support in the analysis and presentation of the materials at the TECHVAC2020 conference (www.techvac.org accessed on 17 December 2021). We wish to thank all the authors who contributed to this issue and members of the Program Committee of TECHVAC2020 for their expert assistance. Funding Information: The authors gratefully acknowledge the Department of Science and Technology fund and grant #U98346 from the National Research Foundation administered South African Research Chair Initiative for Vector-borne and Zoonotic Pathogens Research, RFBR grant #20-04-01034, and Latvian Science Council grants #LZP-2020/2-0376 and #LZP-2021/1-0484 for their support in the analysis and presentation of the materials at the TECHVAC2020 conference (www.techvac.org accessed on 17 December 2021). We wish to thank all the authors who contributed to this issue and members of the Program Committee of TECHVAC2020 for their expert assistance.Until December 2019, we were living in the world of successfully functioning vaccines and vaccination programs [...].publishersversio

Proceedings of the Online Conference “Vaccines and Vaccination during and Post COVID Pandemics” (7–9 December 2022)

Funding Information: The online conference VAC&VAC 2022 gathered about 150 participants from Latvia, Sweden, Italy, the USA, South Korea, South Africa, Netherlands, China, India, Tanzania, Denmark, Germany, Lithuania, and San Marino. Among the participants were academic researchers, public health specialists, and industry representatives, and one-fourth were medical students and PhD students. The conference was supported by the Latvian Council of Science grant 2021/1-0484, Riga Stradins University, the National Cancer Institute “Fondazione Pascale” (Naples, Italy), the International Society for Vaccines ( https://isv-online.org/ , accessed on 27 June 2023), and the MDPI Journal Vaccines. Publisher Copyright: © 2023 by the authors.The COVID-19 pandemic put focus on various aspects of vaccine research and development. These include mass vaccination strategies, vaccination compliance and hesitancy, acceptance of novel vaccine approaches, preclinical and animal models used to assess vaccine safety and efficacy, and many other related issues. These issues were addressed by the international online conference “Vaccines and Vaccination During and Post COVID Pandemics” (VAC&VAC 2022) held on the platform of Riga Stradins University, Riga, Latvia. Conference was supported by the International Society for Vaccines, the National Cancer Institute “Fondazione Pascale” (Naples, Italy), and the scientific journal VACCINES (mdpi). VAC&VAC 2022 attracted nearly 150 participants from 14 countries. This report summarizes conference presentations and their discussion. Sessions covered the topics of (1) COVID-19 vaccine development, evaluation, and attitude towards these vaccines, (2) HPV and cancer vaccines, (3) progress and challenges of HIV vaccine development, (4) new and re-emerging infectious threats, and (5) novel vaccine vehicles, adjuvants, and carriers. Each session was introduced by a plenary lecture from renowned experts from leading research institutions worldwide. The conference also included sessions on research funding and grant writing and an early career researcher contest in which the winners received monetary awards and a chance to publish their results free of charge in the special issue of VACCINES covering the meeting.Peer reviewe

Oxidative stress in infection and consequent disease

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Oncogenic Effects of HIV-1 Proteins, Mechanisms Behind

Funding Information: Funding: This study was supported the Russian Fund for Basic Research grants 17_54_30002 and 20‐04‐01034 to M.I., Latvian Science Council grants LZP‐2018/2‐0308 and LZP‐2020/2‐0376 to M.I., Funding Information: and NCI R01CA 217715 to J.P.The work of Francesca Chiodi is supported by a grant from the Swe‐ dish Medical Research Council (Francesca Chiodi; Vetenskapsrådet 2019‐01169). Publisher Copyright: © 2021 by the authors.People living with human immunodeficiency virus (HIV-1) are at increased risk of developing cancer, such as Kaposi sarcoma (KS), non-Hodgkin lymphoma (NHL), cervical cancer, and other cancers associated with chronic viral infections. Traditionally, this is linked to HIV-1-induced immune suppression with depletion of CD4+ T-helper cells, exhaustion of lymphopoiesis and lymphocyte dysfunction. However, the long-term successful implementation of antiretroviral therapy (ART) with an early start did not preclude the oncological complications, implying that HIV-1 and its antigens are directly involved in carcinogenesis and may exert their effects on the background of restored immune system even when present at extremely low levels. Experimental data indicate that HIV-1 virions and single viral antigens can enter a wide variety of cells, including epithelial. This review is focused on the effects of five viral proteins: envelope protein gp120, accessory protein negative factor Nef, matrix protein p17, transactivator of transcription Tat and reverse transcriptase RT. Gp120, Nef, p17, Tat, and RT cause oxidative stress, can be released from HIV-1-infected cells and are oncogenic. All five are in a position to affect “innocent” bystander cells, specifically, to cause the propagation of (pre)existing malignant and malignant transformation of normal epithelial cells, giving grounds to the direct carcinogenic effects of HIV-1.Peer reviewe

Alphavirus‐driven interferon gamma (IFNG) expression inhibits tumor growth in orthotopic 4T1 breast cancer model

Funding Information: Funding: This research was funded by the Latvian Council of Science, project title “Functional Programming of Tumor‐Associated Macrophages with Viral Immunotherapy Vectors in Breast Cancer Model”, project number lzp‐2018/1‐0208. Funding Information: Acknowledgments: The authors would like to thank Zane Simsone, Dace Pjanova, and Felikss Rumnieks for confocal microscopy. The authors thank the Latvian Council of Science for funding of this research (project number LZP‐2018/1‐0208). O.T., J.J., and M.I were additionally supported by the project “New Approach to Active Immunotherapy of Hepatitis C‐Related Cancer (LIVE®VAC)”, project number LZP‐2018/2‐0308. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.Interferon gamma (IFNg) is a pleiotropic cytokine that can potentially reprogram the tumor microenvironment; however, the antitumor immunomodulatory properties of IFNg still need to be validated due to variable therapeutic outcomes in preclinical and clinical studies. We developed a replication‐deficient Semliki Forest virus vector expressing IFNg (SFV/IFNg) and evaluated its immunomodulatory antitumor potential in vitro in a model of 3D spheroids and in vivo in an immunocompetent 4T1 mouse breast cancer model. We demonstrated that SFV‐derived, IFN‐g‐stimulated bone marrow macrophages can be used to acquire the tumoricidal M1 phenotype in 3D nonattached conditions. Coculturing SFV/IFNg‐infected 4T1 spheroids with BMDMs inhibited spheroid growth. In the orthotopic 4T1 mouse model, intratumoral administration of SFV/IFNg virus particles alone or in combination with the Pam3CSK4 TLR2/1 ligand led to significant inhibition of tumor growth compared to the administration of the control SFV/Luc virus particles. Analysis of the composition of intratumoral lymphoid cells isolated from tumors after SFV/IFNg treatment revealed increased CD4+ and CD8+ and decreased T‐reg (CD4+/CD25+/FoxP3+) cell populations. Furthermore, a significant decrease in the populations of cells bearing myeloid cell markers CD11b, CD38, and CD206 was observed. In conclusion, the SFV/IFNg vector induces a therapeutic antitumor T‐cell response and inhibits myeloid cell infiltration in treated tumors.publishersversionPeer reviewe

The Molecular Interplay between Human Oncoviruses and Telomerase in Cancer Development

Funding Information: This work was supported by the Italian Ministry of Health Ricerca Corrente 2022 Grant L1/10. M.I. Isaguliants was supported by the Latvian Science Fund, project LZP 2021/1-0484. Publisher Copyright: © 2022 by the authors.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.publishersversionPeer reviewe

Oxidative Stress during HIV Infection : Mechanisms and Consequences

Publisher Copyright: © 2016 Alexander V. Ivanov et al.It is generally acknowledged that reactive oxygen species (ROS) play crucial roles in a variety of natural processes in cells. If increased to levels which cannot be neutralized by the defense mechanisms, they damage biological molecules, alter their functions, and also act as signaling molecules thus generating a spectrum of pathologies. In this review, we summarize current data on oxidative stress markers associated with human immunodeficiency virus type-1 (HIV-1) infection, analyze mechanisms by which this virus triggers massive ROS production, and describe the status of various defense mechanisms of the infected host cell. In addition, we have scrutinized scarce data on the effect of ROS on HIV-1 replication. Finally, we present current state of knowledge on the redox alterations as crucial factors of HIV-1 pathogenicity, such as neurotoxicity and dementia, exhaustion of CD4+/CD8+ T-cells, predisposition to lung infections, and certain side effects of the antiretroviral therapy, and compare them to the pathologies associated with the nitrosative stress.publishersversionPeer reviewe

Oxidative stress, a trigger of hepatitis C and B virus-induced liver carcinogenesis

Virally induced liver cancer usually evolves over long periods of time in the context of a strongly oxidative microenvironment, characterized by chronic liver inflammation and regeneration processes. They ultimately lead to oncogenic mutations in many cellular signaling cascades that drive cell growth and proliferation. Oxidative stress, induced by hepatitis viruses, therefore is one of the factors that drives the neoplastic transformation process in the liver. This review summarizes current knowledge on oxidative stress and oxidative stress responses induced by human hepatitis B and C viruses. It focuses on the molecular mechanisms by which these viruses activate cellular enzymes/systems that generate or scavenge reactive oxygen species (ROS) and control cellular redox homeostasis. The impact of an altered cellular redox homeostasis on the initiation and establishment of chronic viral infection, as well as on the course and outcome of liver fibrosis and hepatocarcinogenesis will be discussed The review neither discusses reactive nitrogen species, although their metabolism is interferes with that of ROS, nor antioxidants as potential therapeutic remedies against viral infections, both subjects meriting an independent review.publishersversionPeer reviewe

ATM and atr expression potentiates hbv replication and contributes to reactivation of hbv infection upon DNA damage

Funding Information: Funding: This work was performed within RSF grant no. 16-15-10426. Funding Information: National Medical Research Center of Tuberculosis and Infectious Diseases, Ministry of Health, Moscow 127994, Russia; [email protected] (S.B.); [email protected] (V.C.) Institute of Immunology, Federal Medical Biological Agency, Moscow 115522, Russia NF Gamaleya Research Center of Epidemiology and Microbiology, Moscow 123098, Russia; [email protected] (E.B.); [email protected] (I.G.); [email protected] (M.I.) Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of Russian Academy of Sciences, Moscow 108819, Russia Sechenov First Moscow State Medical University, Moscow 119146, Russia; [email protected] Department of Pathology, Riga Stradins University, LV-1007 Riga, Latvia Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-171 76 Stockholm, Sweden Izmerov Research Institute of Occupational Health, Gene Engineering and Biotechnology, Moscow 105275, Russia; [email protected] (I.G.); [email protected] (F.U.); [email protected] (A.N.) Central Research Institute of Epidemiology, Moscow 111123, Russia Correspondence: [email protected] (A.K.); [email protected] (D.K.) Publisher Copyright: © 2019 by the authors.Chronic hepatitis B virus infection (CHB) caused by the hepatitis B virus (HBV) is one of the most common viral infections in the world. Reactivation of HBV infection is a life-threatening condition observed in patients with CHB receiving chemotherapy or other medications. Although HBV reactivation is commonly attributed to immune suppression, other factors have long been suspected to play a role, including intracellular signaling activated in response to DNA damage. We investigated the effects of DNA-damaging factors (doxorubicin and hydrogen peroxide) on HBV reactivation/replication and the consequent DNA-damage response. Dose-dependent activation of HBV replication was observed in response to doxorubicin and hydrogen peroxide which was associated with a marked elevation in the mRNA levels of ataxia-telangiectasia mutated (ATM) and ATM- and RAD3-related (ATR) kinases. Downregulation of ATM or ATR expression by shRNAs substantially reduced the levels of HBV RNAs and DNA. In contrast, transcriptional activation of ATM or ATR using CRISPRa significantly increased HBV replication. We conclude that ATM and ATR are essential for HBV replication. Furthermore, DNA damage leading to the activation of ATM and ATR transcription, results in the reactivation of HBV replication.publishersversionPeer reviewe

DNA immunization site determines the level of gene expression and the magnitude, but not the type of the induced immune response

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