Cell Vaccine Research Articles

Phase I Study of Adjuvant Allogeneic GM-CSF-Transduced Pancreatic Tumor Cell Vaccine, Low Dose Cyclophosphamide, and SBRT followed by FFX in High-Risk Resected Pancreatic Ductal Adenocarcinoma.

Local and distant progression remain common following resection of resectable pancreatic ductal adenocarcinoma (PDAC) despite adjuvant multiagent chemotherapy. We report a prospective institutional phase I trial incorporating adjuvant GVAX vaccine, low-dose cyclophosphamide (Cy) and SBRT followed by FOLFIRINOX (FFX) among patients who underwent resection of high-risk PDAC. The study design was a modified 3+3. Cohort 1 received 5-fraction SBRT to 33 Gy to the tumor bed and 25 Gy to elective nodes followed by 6 cycles of full dose FFX. After toxicity review, cohort 2 had SBRT and were switched to modified FFX (mFFX). Cohort 3 had 1 cycle of Cy/GVAX followed by SBRT, mFFX, and 4 cycles of maintenance Cy/GVAX with 6-month Cy/GVAX boosts until progression. 19 patients were enrolled with a median follow-up of 36.2 months. To be eligible, patients were required to have close/positive margins (within ≤1 mm) (71%) and/or lymph node metastasis (79%). Overall, 63% of patients had both. In cohort 1, 67% of patients received 6 cycles of FFX; in cohort 2, 75% received 6 cycles of modified FFX. In cohort 3, 12 patients received the first dose of Cy/GVAX and SBRT with 10 individuals (83%) receiving 6 cycles of mFFX. Cohort 3 had acceptable levels of grade ≥3 thrombocytopenia, neutropenia, and diarrhea after two cycles of mFFX. Median OS/DFS for the overall cohort and cohort 3 was 36.2/18.2 months and 61.3/24.1 months, respectively. 1-year and 2-year OS for cohort 3 was 83%/75%, respectively. At last follow-up (median= x), 5 patients were alive (42%) in cohort 3. This is the first prospective trial to evaluate adjuvant GVAX, Cy, SBRT, and mFFX in resected PDAC patients with high-risk features. This combination regimen was well tolerated with limited toxicity and promising survival outcomes, warranting future studies to validate this regimen in the adjuvant setting.

The Processuality of ‘Sex’ in Biomedicine: Exploring Stem Cell Research, Cancer Medicine and Vaccine Safety Research

Incorporating sex into biomedical research is envisioned as key to addressing inequalities in health. However, feminist research suggests that it is a complicated task. This is, we argue, especially the case with research that seeks to mobilise sex across different scales involving bodies, samples and populations to provide a basis for personalised biomedical prevention and treatment. Through case studies from stem cell research, cancer medicine and vaccine safety research, we analyse how sex is enacted, foregrounded and sidelined at different stages of research. We argue that sex becomes suspended between individual bodies, samples and population groups, and that this postpones biomedical analysis of sex differences in health. Yet, research on sex differences in complex embodied processes, such as drug metabolism or immunity, appears as a future potentiality. This potentiality shapes research practices that may open biomedicine towards multi-disciplinary study settings that bring together physiological and social dimensions of bodily difference.

IMMU-61. THE LAST OF US: A FUNGI BASED DENDRITIC CELL VACCINE

Abstract BACKGROUND Glioblastoma (GBM) is the most prevalent primary malignant brain tumor in adults. The current standard treatment for newly diagnosed GBM involves maximal surgical resection followed by radiotherapy and temozolomide. Despite these interventions, the median overall survival for GBM patients remains approximately 15 months, highlighting the critical need for innovative therapeutic approaches. OBJECTIVE Our laboratory has previously developed a subcutaneous autologous tumor vaccine incorporating irradiated (IR) tumor cells with phagocytosis-stimulating ligands (Mannan-BAM), toll-like receptor (TLR) agonists, and an immunostimulant anti-CD40 antibody (collectively termed MBT). This combination has shown efficacy in mouse models of colon carcinoma, breast cancer, melanoma, and, more recently, gliomas. Our study aimed to create a dendritic cell (DC) vaccine using this strategy. METHODS To evaluate whether MBT could induce the maturation of DCs in vitro, we harvested BMDCs from mice and co-cultured them in the presence of MBT-tagged irradiated tumor cells. We then analyzed the maturation markers using flow cytometry and assessed cytokine production via ELISA. To test the efficacy of this approach in vivo, we utilized two different murine glioma models (SB28 and GL261). RESULTS Using flow cytometry, we observed a significant upregulation of important co-stimulatory molecules. Additionally, ELISA analysis demonstrated that MBT-treated DCs significantly increased the secretion of Type 1 cytokines while limiting the secretion of the regulatory cytokine IL-10. MBT-primed DCs combined with immune checkpoint inhibitor PD-1 increased mouse survival in a glioma model compared to WT mice. However, mice eventually succumbed to cerebral edema. Histology demonstrated significant treatment effects. CONCLUSION Our results demonstrate that MBT effectively matures DCs ex-vivo. Further research is required to immunophenotype the response to vaccination in glioma models and explore ways to overcome resistance.

TMIC-45. CYTOMEGALOVIRUS PP65 ANTIGEN EXPRESSION FOLLOWING PP65-SPECIFIC DENDRITIC CELL VACCINATION IN MATCHED PRIMARY AND RECURRENT GLIOBLASTOMA SPECIMENS

Abstract BACKGROUND Human cytomegalovirus (HCMV) expression in glioblastoma (GBM) has been corroborated by multiple independent laboratories. HCMV genes have been directly linked to GBM cell proliferation, invasion, and angiogenesis. The HCMV tegument protein pp65 has served as a tumor-specific antigen in serial pp65 RNA-pulsed autologous dendritic cell (DC) vaccine trials. Here we report pp65 expression in matched primary and recurrent GBM samples from those trials following pp65-DC vaccination. METHODS Paired GBM specimens were collected from patients receiving pp65-DC vaccines according to ATTAC and ATTAC-GM clinical trials (NCT00639639). Of 23 treated patients, 9 cases were available for analysis. Formalin-fixed paraffin-embedded specimens were mounted on glass slides and stained for pp65 via immunohistochemistry (IHC). CD31 served as a control for tissue quality and to investigate the role of pp65 co-staining in the tumor perivascular niche. RESULTS Of 9 available cases, 5 were excluded due to poor tissue quality/absent CD31 staining on aged slides. Among the remaining four cases, three showed pp65 staining in non-vascular and perivascular areas within both primary and recurrent samples. However, recurrent specimens of these positive cases demonstrated a clear reduction in both intensity and distribution of pp65 staining within non-vascular regions but retained a strong positivity within the perivascular space. The fourth case showed absent pp65 staining and only weakly positive CD31 staining in both primary and recurrent specimens. Necrotic areas within pp65-positive slides showed minimal to no pp65 staining. CONCLUSIONS This study confirms HCMV pp65 expression in both primary and recurrent GBM following pp65-DC vaccination, with an interesting phenomenon of retained pp65 expression specifically in the perivascular niche. These findings support the role of HCMV in GBM angiogenesis and tumor progression as well as mechanisms of immune evasion following single antigen vaccine platforms. Our study reinforces the importance of tissue quality for proper HCMV detection in GBM.

BIOS-05. PEPTIDE-BASED VACCINES VERSUS DENDRITIC CELL-BASED VACCINE THERAPIES FOR PATIENTS WITH GLIOBLASTOMA: A NETWORK META-ANALYSIS OF CONTROLLED CLINICAL TRIALS

Abstract BACKGROUND Glioblastoma (GBM) is the most prevalent primary CNS malignancy in adults, often with a bleak prognosis. Reports suggest the efficacy of dendritic cell vaccines (DCV) and peptide vaccines in extending overall survival (OS). We aimed to compare their efficacy using network meta-analysis (NMA). METHODS We systematically searched PubMed, Cochrane database, SCOPUS, and Clinicaltrials.gov up to February 2024 for controlled trials on DCV or peptide vaccines for GBM. NMA was conducted using the frequentist approach to obtain direct and indirect comparisons of each vaccine. Pairwise analyses were performed using the inverse variance method, comparing each vaccine’s efficacy. PEPvIII-KLH and Rindopepimut were merged into “Peptide-based vaccines” [PEP], and standard of care (SOC) and (Placebo + SOC) were merged. Primary outcome: hazard ratio (HR) of overall survival with 95% confidence intervals. RESULTS Analysis included 5 studies with 451 patients (vaccine arm) and 445 controls, with SOC/[Placebo + SOC] as reference. Common effects model showed DCV + SOC significantly reduced the HR to 0.3385 [0.1753; 0.6539], while the peptide-based vaccine + SOC reduced the HR to 0.8276 [0.6960; 0.9840]. In the random effects model, DCV + SOC had an HR of 0.3132 [0.0839; 1.1688], and the peptide-based vaccine + SOC had an HR of 0.3888 [0.1383; 1.0928]. Heterogeneity: tau^2 = 0.6473, tau = 0.8045, I^2 = 77.7% [39.5%; 91.8%]. In a pairwise meta-analysis comparing the DCV+SOC and SOC/[Placebo + SOC] consisting of 2 trials, the common and random effects models both estimated an HR of 0.3385 [0.1753; 0.6539, I^2 = 0.0%]. Comparing the PEP+SOC and SOC/[Placebo + SOC] based on 3 trials, the common effect model estimated an HR of 0.8276 [0.6960; 0.9840], while the random effects model estimated an HR of 0.3874 [0.1360; 1.1039, I^2 = 84.4%]. CONCLUSION Based on current evidence, DCV vaccines perform better than peptide-based vaccines in reducing mortality in GBM patients. Further trials are required to validate their efficacies.

CTIM-27. DOC1021 CELL-BASED VACCINATION AS ADJUVANT THERAPY FOR GLIOBLASTOMA: PHASE I CLINICAL TRIAL ANALYSIS

Abstract Glioblastoma is an aggressive tumor for which median survival remains 14-18 months despite aggressive standard of care. Cellular immunotherapy approaches have recently shown promise. Homologous antigenic loading is an ex-vivo technique that leverages p38MAPK and mTORC1 signaling cascades to initiate powerful cDC1-like skewing in monocyte-derived dendritic cells, leading to downstream induction of tissue-infiltrating, cytolytic effector memory T-cells. This open-label phase I clinical trial evaluated the autologous dendritic cell vaccine DOC1021 prepared through homologous antigenic loading and administered bilaterally near the deep cervical lymph nodes. Three courses of vaccine were administered every 2 weeks after completion of chemoradiation, adjuvanted concurrently with six weeks of weekly type I interferon. Four dose levels from 3.5x106 to 3.6x107 total vaccine cells were tested. Tumor progression prior to vaccination was not an exclusion criterion. Sixteen newly diagnosed IDH-WT patients completed treatment, median age 63 years and 94% MGMTp unmethylated. The most common related AEs were grade 1 injection-site reactions and grade 1-3 fatigue and urticaria. No DLTs were observed. Immunohistochemistry of tumors derived from early post-vaccination second resections showed enhanced CD8+ T-cell infiltration and pathologic findings consistent with residual rather than relapsed GBM in 2/3 patients. Analysis of post-vaccination PBMC in dose level cohorts 2-4 indicated expansion of both CD4+ (13/13) and CD8+ (11/13) central memory T-cell compartments (p<0.002 and p<0.05, respectively) as well as expansion of CD8+CD127+ T-cells (12/13; p<0.001). Among three patients for whom tissue was obtained pre- and post-vaccination, clinical outcomes correlated with Visium spatial transcriptomic analysis. Median survival for the MGMTp unmethylated cohort (n=15) has not yet been reached but is statistically greater (p<0.05) than that of matched historic controls. The results indicate that DOC1021 is safe, can be effectively integrated within existing standards of care and is potentially efficacious in a challenging patient population.

CTIM-17. INDIVIDUALIZED MULTIMODAL IMMUNOTHERAPY (IMI) FOR ADULTS WITH DIFFUSE MIDLINE GLIOMA OR DIFFUSE HEMISPHERIC GLIOMA

Abstract Diffuse Midline Glioma (DMG, H3K27 mutant) and Diffuse Hemispheric Glioma (DHG, H3G34 mutant) are rare malignant CNS tumors with dismal prognosis. We retrospectively searched in our database for adults (>18y) with molecularly define DMG/DHG, treated between May 2015 and 2024 with IMI as part of first-line treatment. Amongst 157 IMI-treated malignant glioma patients, four patients fit these restrictions, pointing to scarce experience of IMI for DMG/DHG adult patients. HM (M, 29y) was diagnosed with a DMG in the pons. He received radiochemotherapy, and continued after 2x TMZm with BRAF-MEK-inhibition therapy. He received one IO-Vac® dendritic cell vaccine but showed fast progression thereafter. He died 9 months after diagnosis. GJE (F, 28y) had a DMG at the corpus callosum. She received radiochemotherapy and 6x TMZm, followed by 2x IO-Vac® and 3x maintenance immunogenic cell death (ICD) immunotherapy (NDV injections, sessions of modulated electrohyperthermia), combined with WT1 and H3K27M long-peptide vaccines. She progressed after 20 months, for which a new IO-Vac® and an H3K27M short- and long-peptide vaccine were given. She died 5 months later. Overall Survival (OS) was 26 months after initial diagnosis. JD (F, 27y) was diagnosed with a DMG in C2-C6. She received radiochemotherapy followed by IMI alone, including 2x IO-Vac®, one ICD immunotherapy, and four doses of anti-PD1. She died 17 months later, making OS 27 months after diagnosis. VJ (F, 21y) had a DHG in the left cerebrum. She received radiochemotherapy and 12 cycles of maintenance TMZ (TMZm), between which ICD immunotherapy was inserted each time. Afterwards, she received two IO-Vac®. Finally, she received ICD immunotherapy (6x) combined with checkpoint inhibitors (4x anti-CTLA4, 10x anti-PD1). Thirty months after diagnosis, she is in remission with a stable Health Utility Index of 0.72. IMI might have contributed to a better OS in three out of four DMG/DHG patients, and should be explored further as part of the treatment for these patients.

Exogenous or in situ vaccination to trigger clinical responses in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDA) is a lethal disease for which remarkable therapeutic resistance is the norm. Conventional immunotherapies, like immune checkpoint inhibitors, show limited efficacy in PDA due to a remarkably immunosuppressive tumor microenvironment (TME) and systemic inflammation. This review discusses the potential of both exogenous and in situ vaccination strategies to overcome these barriers and enhance anti-tumor immunity in PDA. Exogenous vaccines, including whole-cell, dendritic cell, peptide, and nucleic acid-based vaccines, have shown varying degrees of promise but face challenges related to antigen selection, production complexities, and patient-specific factors. In contrast, in situ vaccination strategies leverage conventional cytotoxic therapies, such as chemotherapy and radiation therapy, to induce immunogenic cell death and modulate the TME with the aim to stimulate anti-tumor immunity. While preclinical studies support the use of in situ vaccination, balancing the stimulatory and inhibitory effects is likely fundamental to eliciting productive anti-tumor responses in patients. Ongoing research seeks to identify new innovative strategies that can harness the endogenous immune response and trigger in situ vaccination. Overall, while both vaccination approaches offer significant potential, further research and clinical trials will be needed to optimize these strategies for improving patient outcomes in PDA.

Intradermal Delivery of Cell Vaccine via Ice Microneedles for Cancer Treatment.

The living tumor cell vaccine (TCV) holds a promise for cancer immunotherapy. Microneedle arrays provide a tool to improve the immune response of vaccines by the intradermal administration in a painless manner. However, it remains challenges for microneedle arrays to deliver the living TCV intradermally. Here, an ice microneedle array delivered living TCVsis shown with sustained granulocyte-macrophage colony-stimulating factor (GM-CSF) secretion for cancer treatment. The ice microneedle array is composed of ice microneedles and a matching polymer holder, which are customized fabricated by a static optical projection lithography (SOPL) technique. The living TCV consisted ofirradiated melanoma cells transfected with nanoparticle-mediated GM-CSF plasmids. After the living TCV is readily loaded into the ice microneedle via a cryopreservation process, it couldbe efficiently delivered into the dermis by the microneedle device. Compared to the subcutaneous injection, intradermal administration led to the recruitment of more dendritic cells at the vaccination site and the increased infiltration of CD8+ T cells in the tumor. The ice microneedle array deliveres intradermal TCVssignificantly inhibited melanoma growth and effectively prevented melanoma recurrence without obvious side effects. This work demonstrates a promising TCVs for melanoma treatment, which will inspire the future of cancer immunotherapy.

Necroptosis as a consequence of photodynamic therapy in tumor cells.

Photodynamic therapy (PDT) is an alternative to cancer treatment, demonstrating selectivity and significant cytotoxicity on malignant tissues. Such therapy involves two nontoxic components: photosensitizer (PS) and non-ionizing radiation. In optimal dosage combinations, PDT causes cellular and tissue effects by oxygen-dependent processes, leading tumor cells to regulated cell death pathways. Regulated necrosis, called necroptosis, can be triggered by PDT and is characterized by caspase-8 inhibition and RIPK1, RIPK3, and MLKL activities, leading to plasma membrane pores formation with subsequent cellular content release into the extracellular space. For this review, studies accessed by PubMed describing the relation between necroptosis and PDT were summarized. The results showed that PDT can trigger necroptosis mechanisms in different tumor cells. Moreover, a mix of different cell death types can co-occur. It is also important to highlight that necroptosis triggered by PDT is related to damage-associated molecular patterns (DAMPs) release, involving immunogenic cell death and vaccination. The cell death response is directly related to the photosensitizer chemical characteristics, concentration, incubation time, cellular location, and irradiation parameters. The synergism among all cell death types is an excellent advantage for avowing tumor resistance mechanisms and developing new solutions.

Immunogenicity of two-dose sinopharm BBIB-CorV vaccine in Morocco: One-year follow-up and neutralizing activity against severe acute respiratory syndrome coronavirus 2 variants of concern.

This study aimed to evaluate the immunogenicity of a two-dose Sinopharm BBIB-CorV (Vero cells) vaccine against SARS-CoV-2, at 28 days, 6 months, and 1-year postvaccination. And assess the capacity of two-dose vaccine recipients to neutralize SARS-CoV-2 strains B.1 (Wuhan/D614G), B.1.1.7 (Alpha), AY.33 (Delta), or BA.5.2.2 (Omicron) variants of concern (VOCs). A prospective matched case-control cohort study was conducted at the Military Hospital of Rabat, Morocco between February 2021 and 2022. Immunogenicity was evaluated by standard Microneutralization (MN) assay against four variants (Wuhan D614G, Alpha, Delta, and Omicron). The overall positive neutralizing rates for vaccine recipients against B.1 D614G were 72.09%, 74.82%, and 75.19% on 28-, 180-, 365- day respectively. The proportion of NAbs targeting the Wuhan D614G, and Alpha variants under the BBIBP-CorV vaccination was high on Day 28- and 6 months postvaccination. The immunogenic response to the newly emerging SARS-CoV-2 variants of concern (VOCs), such as Delta and Omicron was comparatively reduced. As a result, it is recommended that additional boost vaccinations be considered.

A novel anti-CTLA-4 nanobody-IL12 fusion protein in combination with a dendritic cell/tumour fusion cell vaccine enhances the antitumour activity of CD8+ T cells in solid tumours.

We previously developed a nanobody targeting CTLA-4 and demonstrated that it can boost antitumour T-cell responses in vitro; however, the resulting responses after the injection of T cells into cancer models are usually weak and transient. Here, we explored whether fusing our nanobody to IL-12 would enable it to induce stronger, longer-lasting T-cell immune responses after exposure to immature dendritic cell and tumour cell fusions. The fusion protein enhanced the response of CD8+ T cells to tumour antigens in vitro and led to stronger, more persistent immune responses after the T cells were injected into mice bearing different types of xenografts. Our in vitro and in vivo results suggest the anticancer potential of our nanobody-interleukin fusion system and support the clinical application of this fusion approach for various nanobodies.

Triple-negative breast cancer-derived exosomes change the immunological features of human monocyte-derived dendritic cells and influence T-cell responses.

Triple-negative breast cancer (TNBC) exhibits a lower survival rate in comparison to other BC subtypes. Utilizing dendritic cell (DC) vaccines as a form of immunotherapy is becoming a promising new approach to cancer treatment. However, inadequate immunogenicity of tumor antigens leads to unsatisfactory effectiveness of the DC vaccines. Exosomes are the basis for the latest improvements in tumor immunotherapy. This study examined whether TNBC-derived exosomes elicit immunogenicity on the maturation and function of monocyte-derived DCs and the impact of the exosome-treated monocyte-derived DCs (moDCs) on T cell differentiation. exosomes were isolated from MDA-MB-231 TNBC cancer cells and characterized. Monocytes were separated from peripheral blood mononuclear cells and differentiated into DCs. Then, monocyte-derived DCs were treated with TNBC-derived exosomes. Furthermore, the mRNA levels of the genes and cytokines involved in DC maturation and function were examined using qRT-PCR and ELISA assays. We also cocultured TNBC-derived exosome-treated moDCs with T cells and investigated the role of the treatment in T cell differentiation by evaluating the expression of some related genes by qRT-PCR. The concentration of the cytokines secreted from T cells cocultured with exosome-treated moDCs was quantified by the ELISA assays. Our findings showed that TNBC-derived exosomes induce immunogenicity by enhancing moDCs' maturation and function. In addition, exosome-treated moDCs promote cocultured T-cell expansion by inducing TH1 differentiation through increasing cytokine production. TNBC-derived exosomes could improve vaccine-elicited immunotherapy by inducing an immunogenic response and enhancing the effectiveness of the DC vaccines. However, this needs to be investigated further in future studies.

Zika virus T-cell based 704/DNA vaccine promotes protection from Zika virus infection in the absence of neutralizing antibodies.

Zika virus (ZIKV) and dengue virus (DENV) are closely related flaviviruses co-circulating in the same endemic areas. Infection can raise cross-reactive antibodies that can be either protective or increase risk of severe disease, depending on the infection sequence, DENV serotype and elapsed time between infection. On the contrast, T cell-mediated immunity against DENV and ZIKV is considered protective. Therefore, we have developed a T cell vaccine enriched in immunodominant T cell epitopes derived from ZIKV and evaluated its immunogenicity and efficacy against ZIKV and DENV infection. Mice were vaccinated using DNA vaccine platform using the tetrafunctional amphiphilic block copolymer 704. We show that vaccination of 2 different HLA class I transgenic mice with the ZIKV non-structural (NS) poly-epitope elicits T cell response against numerous ZIKV epitopes. Moreover, vaccination induces a significant protection against ZIKV infection, in the absence of neutralizing or enhancing antibodies against ZIKV. However, vaccination does not induce a significant protection against DENV2. In contrast, immunization with a DENV1-NS poly-epitope induces a significant protection against both DENV1 and DENV2, in the absence of humoral immunity. Taken together, we have shown that T-cell based vaccination could protect against multiple flavivirus infections and could overcome the complexity of antibody-mediated enhancement.

Mechanotransduction-Piloted Whole-Cell Vaccines for Spatiotemporal Modulation of Postoperative Antitumor Immunity.

Whole tumor cell vaccines hold promise by presenting a broader spectrum of autologous-origin tumor antigens to combat postoperative recurrence and metastasis. However, challenges such as intractable adjuvant modification and obscure interactions with antigen-presenting cells in the postoperative microenvironment impede their translation into effective personalized immunotherapies. In this study, we propose cancer vaccines derived from manganese oxide-immobilized resected tumor cells, featuring whole tumor antigens and adjustable stiffness to modulate interactions with antigen-presenting cells in the postoperative microenvironment. These vaccines effectively stimulate dendritic cell phagocytosis and function through sequential stiffness-mediated mechanotransduction and interferon signaling. We evaluated their efficacy using an orthotopic triple-negative breast cancer mouse model and found that combining the vaccines with radiotherapy effectively inhibits postoperative tumor recurrence and metastasis. Our study underscores the potential of utilizing mechanotransduced adjuvants alongside directly inactivated whole-cell vaccines as a universal solution for preventing postoperative tumor recurrence.

Study on the feasibility of using livestock blood as a fetal bovine serum substitute for cultured meat.

Fetal bovine serum (FBS) accounts for the largest portion of the cost of cultured meat production or cell culture experiments and is highly controversial in terms of animal welfare because it is taken from the fetus of a pregnant cow during slaughtering. Nevertheless, FBS is the most important supplement in the cell culture manufacturing process. This study aimed to develop an FBS substitute from slaughterhouse waste blood to reduce the cost of FBS in cultured meat production through various experiments. Our study successfully demonstrated that adult livestock blood obtained from slaughterhouses can effectively replace FBS. Our substitute, when cultured with bovine myosatellite cells, demonstrated cell growth that was either equivalent to or superior to that of commercial FBS. In the process of muscle generation through differentiation, the substitutes from bovine and chicken formed 70%-75% more bovine muscle compared to the control group using FBS. Furthermore, using the FBS substitute can reduce cell culture costs by approximately 61% compared to using commercial FBS. Therefore, the groundbreaking FBS substitute will not only contribute to the development of technology to mass-produce cultured meat using livestock byproducts but will also lower the production cost of media for experimental cell culture or vaccine production.

Molecular mechanisms of Coxiella burnetii formalin-fixed cellular vaccine reactogenicity.

Local and systemic reactogenic responses to Q-VAX have prevented licensing of this vaccine outside of Australia. These reactogenic responses occur in previously sensitized individuals and have not been well defined at the cellular level, in part because many studies have been done in guinea pigs that have limited molecular tools. We previously characterized a mouse model of reactogenicity where local reaction sites showed an influx of CD8+ and IFNγ-expressing IL17a+ CD4+ T cells consistent with a Th1 delayed-type hypersensitivity. In this study, we determined, using depletion and adoptive transfer experiments, that both anti-Coxiella antibodies and CD4+ T cells were essential for localized reactions at the site of vaccination. Furthermore, IFNγ depletion showed significant histological changes at the local reaction sites demonstrating the essential nature of this cytokine to reactogenicity. In addition to the cells and cytokines required for this response, we determined that whole cell vaccine (WCV) material remained at the site of vaccination for at least 26 weeks post-injection. Transmission electron microscopy (TEM) of these sites demonstrated intact rod-shaped bacteria at 2 weeks post-injection and partially degraded bacteria within macrophages at 26 weeks post-injection. Finally, because small cell variants (SCVs) are an environmentally stable form, we determined that local reactions were more severe when the WCV material was prepared with higher levels of SCVs compared to typical WCV or with higher levels of large cell variant (LCV). These studies support the hypothesis that antigen persistence at the site of injection contributes to this reactogenicity and that anti-Coxiella antibodies, CD4+ T cells, and IFNγ each contribute to this process.

Comprehensive Details on Human Papillomavirus (HPV) Infections and Associated Malignancies: Awareness about Prophylaxis & Treatment Options Available for HPV Infections

Human Papilloma virus (HPV) role has now been widely accepted as a causative agent for cervical as well as head and neck squamous cell carcinomas. Screening and early detection of cervical cancer remains the key element to eradicate this deadly disease. Since it has a long natural history and disease progression, this gave an opportunity for early detection through screening of precancerous lesions which was adopted in high income countries (HIC) like UK which has led to the significant reduction of the cases. Unfortunately, Low- and middle-income countries are facing huge burden because of the lack of effective screening program. FDA approved Cervarix, Gardasil and Gardasil 9 are used as prophylaxis for cervical cancer & genital warts but screening is still essential after vaccination because these vaccines are not effective against all types of HPV types. HPV 16 & HPV 18 are highly oncogenic types and accounts for 70% of cervical cancers. The use of vaccine reduces the risk of getting HPV infection and decrease the rate of morbidity and mortality due to the cervical cancer. In addition to vaccines, many peptides or protein-based & cell or DNA-based vaccines are still in clinical trials; these prevention and management available in vaccines are likely to come up with significant benefits of health in future. Although it’s usually cured by immune system but presence of certain cofactors such as smoking, HIV etc. reduces the probability of an individual to eradicate the infection effectively. The aim of this study is to review literature regarding HPV related infections and malignancies. Moreover, it will make individuals aware about prophylaxis & treatment options available for HPV infection. This review article evaluates the HPV related diseases, there screening, evaluation and management currently available. Bangladesh Journal of Medical Science Vol. 23 No. 04 October’24 Page : 967-983

A subunit vaccine of largemouth bass (Micropterus salmoides) with baculovirus-expressed largemouth bass ranavirus (LMBRaV) major capsid protein induces protective immunity against LMBRaV infection

Largemouth Bass Ranavirus (LMBRaV) is associated with large mortalities of farmed Largemouth Bass (Micropterus salmoides), which has caused huge economic loss to its aquaculture in China. The major capsid protein (MCP), an effective antigen to induce a specific immune response in iridovirus, has been widely used as immunogen in vaccination experiments. In this study, we constructed the recombinant baculovirus autographa californica multiple nucleopolyhedrovirus-MCP (AcMNPV-MCP) through Bac-to-Bac baculovirus expression system and expressed MCP as a subunit vaccine in insect cells. Recombinant baculovirus was verified using PCR and the virus titer was calculated as 50 % tissue culture infectious dose (TCID50/mL) using the Reed-Muench method. After confirmed by western blot, the recombinant MCP was purified from baculovirus-infected cell lysates and injected intraperitoneally (12 µg/fish) into M. salmoides. Liver, spleen and head kidney were collected at indicated times to analyze the expression of anti-viral genes. The result showed that the mRNA expression levels of immune-related genes like interferon related factors and interleukins were significantly up-regulated in AcMNPV-MCP immunized group. Meanwhile, the number of leukocytes in immunized group were significantly higher than that in control group. After immunized for 35 days, M. salmoides were challenged with LMBRaV injection. After infection with LMBRaV, Non-vaccinated groups exhibited a mortality of 100 %, while the survival rate of vaccinated group was up to 63.3 %. qPCR found that the virus load of vaccinated group was significantly lower than that of Non-vaccinated groups. This finding will potentially allow for the development of more target subunit vaccine development against largemouth bass ranavirus.

Dendritic cells pulsed with multifunctional Wilms’ tumor 1 (WT1) peptides combined with multiagent chemotherapy modulate the tumor microenvironment and enable conversion surgery in pancreatic cancer

BackgroundWe aimed to develop a chemoimmunotherapy regimen consisting of a novel Wilms’ tumor 1 (WT1) peptide-pulsed dendritic cell (WT1-DC) vaccine and multiagent chemotherapy and to investigate the safety, clinical outcomes,...