Introduction: While there has been considerable progress in the development of vaccines against SARS-CoV-2, largely based on the S (spike) protein of the virus, less progress has been made with vaccines delivering different viral antigens with cross-reactive potential.
Methods: In an effort to develop an immunogen with the capacity to induce broad antigen presentation, we have designed a multi-patch synthetic candidate containing dominant and persistent B cell epitopes from conserved regions of SARS-CoV-2 structural proteins associated with long-term immunity, termed CoV2-BMEP. Here we describe the characterization, immunogenicity and efficacy of CoV2-BMEP using two delivery platforms: nucleic acid DNA and attenuated modified vaccinia virus Ankara (MVA).
Results: In cultured cells, both vectors produced a main protein of about 37 kDa as well as heterogeneous proteins with size ranging between 25-37 kDa. In C57BL/6 mice, both homologous and heterologous prime/boost combination of vectors induced the activation of SARS-CoV-2-specific CD4 and CD8 T cell responses, with a more balanced CD8 T cell response detected in lungs. The homologous MVA/MVA immunization regimen elicited the highest specific CD8 T cell responses in spleen and detectable binding antibodies (bAbs) to S and N antigens of SARS-CoV-2. In SARS-CoV-2 susceptible k18-hACE2 Tg mice, two doses of MVA-CoV2-BMEP elicited S- and N-specific bAbs as well as cross-neutralizing antibodies against different variants of concern (VoC). After SARS-CoV-2 challenge, all animals in the control unvaccinated group succumbed to the infection while vaccinated animals with high titers of neutralizing antibodies were fully protected against mortality, correlating with a reduction of virus infection in the lungs and inhibition of the cytokine storm.
Discussion: These findings revealed a novel immunogen with the capacity to control SARS-CoV-2 infection, using a broader antigen presentation mechanism than the approved vaccines based solely on the S antigen.
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http://dx.doi.org/10.3389/fimmu.2023.1160065 | DOI Listing |
Immun Inflamm Dis
January 2025
Second Department of Oncology, Guangdong Second Provincial General Hospital, Guangzhou, China.
Background: SET domain-containing protein 4 (SETD4) is a histone methyltransferase that has been shown to modulate cell proliferation, differentiation, and inflammatory responses by regulating histone H4 trimethylation (H4K20me3). Previous reports have demonstrated its function in the quiescence of cancer stem cells as well as drug resistance in several cancers. A limited number of systematic studies have examined SETD4's role in the tumor microenvironment, pathogenesis, prognosis, and therapeutic response.
View Article and Find Full Text PDFJ Clin Invest
January 2025
State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China.
Stimulator of interferon genes (STING) agonists have been developed and tested in clinical trials for their antitumor activity. However, the specific cell population(s) responsible for such STING activation-induced antitumor immunity have not been completely understood. In this study, we demonstrated that endothelial STING expression was critical for STING agonist-induced antitumor activity.
View Article and Find Full Text PDFWorld J Gastrointest Oncol
January 2025
Department of Oncology, Zhangjiagang First People's Hospital, Suzhou 215600, Jiangsu Province, China.
Background: Owing to the absence of specific symptoms in early-stage gastric cancer, most patients are diagnosed at intermediate or advanced stages. As a result, treatment often shifts from surgery to other therapies, with chemotherapy and targeted therapies being the primary options for advanced gastric cancer treatment.
Aim: To investigate both treatment efficacy and immune modulation.
Theranostics
January 2025
Department of Pharmacology, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea.
Adenovirus-based therapies have encountered significant challenges due to host immunity, particularly from pre-existing antibodies. Many trials have struggled to evade antibody response; however, the efficiency of these efforts was limited by the diversity of antibody Fv-region recognizing multiple amino acid sequences. In this study, we developed an antibody-evading adenovirus vector by encoding a plasma-rich protein transferrin-binding domain.
View Article and Find Full Text PDFTheranostics
January 2025
Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
: Tumor associated macrophages (TAMs) are critical components in regulating the immune statuses of the tumor microenvironments. Although TAM has been intensively studied, it is unclear how mitochondrial proteins such as AGK regulate the TAMs' function. : We investigated the AGK function in TAMs using macrophage-specific deficient mice with B16 and LLC syngeneic tumor models.
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