Vaccines最新文献

{"title":"Engineering Universal Cancer Immunity: Non-Tumor-Specific mRNA Vaccines Trigger Epitope Spreading in Cold Tumors.","authors":"Matthias Magoola, Sarfaraz K Niazi","doi":"10.3390/vaccines13090970","DOIUrl":"10.3390/vaccines13090970","url":null,"abstract":"<p><p>The landscape of cancer immunotherapy must shift from personalized neoantigen vaccines toward universal platforms that leverage innate immune activation. This review examines a novel mRNA vaccine strategy that encodes non-tumor-specific antigens, carefully selected pathogen-derived or synthetic sequences designed to transform immunologically \"cold\" tumors into inflamed therapy-responsive microenvironments. Unlike conventional approaches requiring patient-specific tumor sequencing and 8-12-week manufacturing timelines, this platform utilizes pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) to trigger broad innate immune activation through multiple pattern recognition receptors (PRRs). The key therapeutic mechanism is epitope spreading, where vaccine-induced inflammation reveals previously hidden tumor antigens, enabling the immune system to mount responses against cancer-specific targets without prior knowledge of these antigens. Delivered via optimized lipid nanoparticles (LNPs) or alternative polymer-based systems, these vaccines induce epitope spreading, enhance checkpoint inhibitor responsiveness, and establish durable antitumor memory. This approach offers several potential advantages, including immediate treatment availability, a cost reduction of up to 100-fold compared to personalized vaccines, scalability for global deployment, and efficacy across diverse tumor types. However, risks such as cytokine release syndrome (CRS), potential for off-target autoimmunity, and challenges with pre-existing immunity must be addressed. By eliminating barriers of time, cost, and infrastructure, this universal platform could help democratize access to advanced cancer treatment, potentially benefiting the 70% of cancer patients in low- and middle-income countries (LMICs) who currently lack immunotherapy options.</p>","PeriodicalId":23634,"journal":{"name":"Vaccines","volume":"13 9","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12474334/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145178776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"COVID-19 Vaccination Reduces Lower Limb Amputation Rates and Mortality Rate in Patients with Pre-Existing Peripheral Vascular Disease Based on TriNetX Database.","authors":"Shiuan-Tzuen Su, Yu-Hsuan Huang, Jing-Yang Huang, James C-C Wei","doi":"10.3390/vaccines13090969","DOIUrl":"10.3390/vaccines13090969","url":null,"abstract":"<p><p><b>Background:</b> Unvaccinated individuals with peripheral arterial occlusive disease (PAOD) are more likely to develop acute limb ischemia (ALI) following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We assessed the protective effect of the COVID-19 vaccine in preventing ALI in PAOD patients with SARS-CoV-2 infection. <b>Methods:</b> This retrospective cohort study was conducted using the United States TriNetX (Cambridge, MA, USA), using patients with PAOD who were diagnosed with SARS-CoV-2 infection between 1 November 2020 and 31 December 2023. Propensity score matching was performed to adjust for demographic variables, lifestyle factors, medical utilization, and comorbidities. Cox proportional hazards models were used to compare the two matched cohorts. Kaplan-Meier analysis estimated the 3-year cumulative probability of lower limb amputation incidence. We selected 12,948 PAOD patients who received the COVID-19 vaccine and 44,064 PAOD patients who were unvaccinated against COVID-19. <b>Results:</b> A total of 11,822 pairs of COVID-19 vaccinated PAOD patients and unvaccinated individuals were compared. The mean (SD) age was 66.5 (14.1) years; there were 4849 male patients (41%) and 6569 female (55.6%) compared to unvaccinated PAOD patients, and those who received the COVID-19 vaccine had a significantly lower risk of 3-year all-cause mortality (log-rank test, <i>p</i> < 0.001; hazard ratio (HR) was 0.857; 95% CI, 0.796-0.922) and lower limb amputation (log-rank test, <i>p</i> = 0.001, HR = 0.716; 95% CI, 0.587-0.873), though there was no significant difference in ischemic stroke (log-rank test, <i>p</i> = 0.174; HR = 0.958; 95% CI, 0.902-1.019). <b>Conclusions:</b> This study found that patients who received the COVID-19 vaccine had a significantly lower risk of 3-year all-cause mortality and lower limb amputation, though there was no significant difference in ischemic stroke.</p>","PeriodicalId":23634,"journal":{"name":"Vaccines","volume":"13 9","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12474159/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145179058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adjuvant Mucosal Strategies Confer Safe and Effective Immunity Against <i>Mycoplasma pneumoniae</i> and Overcome Vaccine-Associated Enhanced Lung Pathology.","authors":"Zhentao Lei, Dandan Gao, Xiaolong Zhang, Han Cao, Jingping Hu, Yifan Zhou, Ning Luan, Cunbao Liu","doi":"10.3390/vaccines13090968","DOIUrl":"10.3390/vaccines13090968","url":null,"abstract":"<p><strong>Background/objectives: </strong>The global spread of <i>Mycoplasma pneumoniae</i> (MP) poses a significant threat to public health; however, no licensed vaccine for human use is currently available. The development of a safe and effective vaccine is a critical priority. This study systematically evaluated the protective efficacy and safety of an inactivated MP vaccine using different adjuvants and immunization routes.</p><p><strong>Methods: </strong>Mice were immunized with inactivated vaccines via either intramuscular (IM) injection with aluminum hydroxide (alum) or a combination of CpG+QS21 (CQ) or via intranasal (IN) administration of Flagellin from <i>Salmonella Typhimurium</i> (FLA-ST), a potent Toll-like receptor 5 (TLR5) agonist, as a mucosal adjuvant. Vaccine-induced immunogenicity, protective efficacy against MP challenge, and associated lung pathology were assessed.</p><p><strong>Results: </strong>Both IM-vaccinated groups (alum and CQ) exhibited robust systemic immune responses. However, upon subsequent MP challenge, these groups exhibited significant inflammatory pathology in the lung tissues. Notably, the CQ-adjuvanted group displayed severe pulmonary inflammatory infiltration. In stark contrast, compared with the IM-vaccinated group, the IN-immunized group with the FLA-ST mucosal adjuvant achieved significant clearance of MP from the lungs and showed markedly milder histopathological lung damage.</p><p><strong>Conclusions: </strong>Our findings suggest that IM immunization with CQ-adjuvanted inactivated vaccines may represent a suboptimal strategy for MP, given the risk of exacerbating lung immunopathology. Conversely, a mucosal immunization approach using the FLA-ST adjuvant demonstrates considerable promise, offering an effective balance between bacterial clearance and an improved safety profile, highlighting its potential for future MP vaccine development.</p>","PeriodicalId":23634,"journal":{"name":"Vaccines","volume":"13 9","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12474190/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145178846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of COVID-19 on Mucosal Immunity and Antibody Responses in COVID Vaccinees.","authors":"Priya Kannian, Muruganantham Lillimary Eniya, Pasuvaraj Mahanathi, Arul Gracemary, Nagalingeswaran Kumarasamy, Stephen J Challacombe","doi":"10.3390/vaccines13090967","DOIUrl":"10.3390/vaccines13090967","url":null,"abstract":"<p><p><b>Background and Objectives</b>: SARS-CoV-2 infection initiates at mucosal surfaces, and mucosal immunity may influence the nature and severity of infection. Little is known about the induction of mucosal immunity by vaccination in COVID-19 convalescents. <b>Methods</b>: Sera from 205 healthcare workers were collected one month after the first Covishield vaccination and 1/3/6 months after the second vaccination, while paired sera and stimulated whole-mouth fluid (SWMF) was collected 1/3/6 months after the third vaccination (N = 10) and at 0/30/90 days after a COVID-19 episode (N = 8). Anti-SARS-CoV-2 spike antibody detection by ECLIA/ELISA and cytokine detection by ELISA/CBA were performed. <b>Results</b>: One month post-second vaccination, serum antibodies had increased significantly (6-fold) in the COVID-19-naïve group (CNG) but declined (1.5-fold) in the previously COVID-19-exposed group (CEG), who already had high antibody titres. The serum regulatory cytokine IL-10 levels were higher after three antigen exposures (<i>p</i> = 0.0002). New infections (breakthrough infections-BTIs) or reinfections (RIs) with asymptomatic/mild disease occurred in 44% of the CNG and 27% of the CEG (<i>p</i> < 0.01). The mucosal cytokine IL-17 levels were significantly higher in the CEG. Salivary IgG/IgA and secretory IgA antibodies were detectable both after vaccination and COVID-19. Innate cytokines (MIG, MCP-1, IL-8, IL-1β) were higher and sustained in SWMF in contrast to serum. <b>Conclusions</b>: Two vaccinations in the CNG resulted in an antibody boost, but the second vaccination in the CEG induced antibody anergy. Serum/mucosal antibodies declined by six months after vaccination, but the rapid increase at subsequent exposures were indicative of a good T cell/B cell memory response to SARS-CoV-2. A higher percentage of BTI among the CNG than RI among the CEG may indicate better protection due to higher antibody responses in the latter group.</p>","PeriodicalId":23634,"journal":{"name":"Vaccines","volume":"13 9","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12474350/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145178950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunogenicity and Antigenicity of the Recombinant Ectodomain of Rabies Virus Glycoprotein Containing the Human Collagen XVIII Trimerization Domain.","authors":"Izat Smekenov, Gulshat Bayandy, Sanzhar Alybayev, Nuraiym Baltakhozha, Zhanat Batanova, Nurlan Akhmetsadykov, Amangeldy Bissenbaev","doi":"10.3390/vaccines13090971","DOIUrl":"10.3390/vaccines13090971","url":null,"abstract":"<p><p><b>Background</b>: Rabies remains a fatal zoonotic disease, necessitating effective and affordable vaccines. While current vaccines are effective, they require multiple doses and may not induce long-lasting immunity in all settings. The rabies virus glycoprotein (RABV-G) is the principal antigen responsible for eliciting virus-neutralizing antibodies, but its recombinant monomeric forms often suffer from poor immunogenicity due to misfolding and aggregation. <b>Methods</b>: A recombinant trimeric RABV-G ectodomain (rRABV-G-XVIII) was engineered by fusing it to a human collagen XVIII-derived trimerization domain. The protein was expressed in <i>E. coli</i>, purified under denaturing conditions, and refolded. Trimer formation was verified using size-exclusion chromatography. Mice were immunized with rRABV-G-XVIII, with or without adjuvant, and compared to a monomeric form (rRABV-GE). Antigen-specific antibody responses were measured by ELISA, neutralizing activity was assessed, and protective efficacy was evaluated via intracerebral challenge with the CVS-27 rabies strain. <b>Results</b>: rRABV-G-XVIII formed stable trimers and induced strong humoral immune responses, with high ELISA titers and virus-neutralizing activity comparable to an inactivated rabies vaccine. Mice immunized with rRABV-GE showed lower antibody responses and partial protection, which improved with adjuvant. All rRABV-G-XVIII-immunized mice were fully protected against rabies challenge, independent of adjuvant use. <b>Conclusions</b>: Stabilization of RABV-G in its native trimeric conformation markedly improves immunogenicity and protective efficacy. This approach offers a promising strategy for the development of rabies subunit vac-cines with simplified formulations and potential for cost-effective production in bacterial systems.</p>","PeriodicalId":23634,"journal":{"name":"Vaccines","volume":"13 9","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12474313/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145178898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vaccination Coverage in Adult Patients with Inflammatory Bowel Disease: Impact of a Tailored Vaccination Pathway Including COVID-19 and Herpes Zoster in a University Hospital Vaccination Center.","authors":"Roberto Venuto, Caterina Elisabetta Rizzo, Daniela Lo Giudice, Walter Fries, Concetta Ceccio, Francesco Fedele, Raffaele Squeri, Cristina Genovese","doi":"10.3390/vaccines13090961","DOIUrl":"10.3390/vaccines13090961","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Patients with inflammatory bowel disease (IBD) are at increased risk of severe infections, particularly when undergoing immunosuppressive therapy. Vaccination is a key preventive strategy, but coverage in this group is often suboptimal. This study evaluated vaccination coverage among IBD patients at diagnosis/referral and after admission to a structured hospital-based vaccination pathway. <b>Methods</b>: We conducted an observational study (February 2022-February 2025) at the Vaccination Center (VC) of the University Hospital \"G. Martino\" in Messina, Italy. Adult IBD patients referred by gastroenterologists were assessed for vaccination status using hospital and regional registries, and personalized schedules were developed based on Italian National Vaccine Prevention Plan guidelines. Descriptive statistics were applied to assess baseline and post-intervention vaccination coverage. <b>Results</b>: Of 154 participants (mean age 64 years; 51.9% male), 55.4% were on immunosuppressive therapy. Baseline coverage was heterogeneous: influenza, 6.5%; PCV13, 25.5%; PPV23, 26.6%; herpes zoster, 62.3%; and COVID-19 primary cycle, 79.6%. After enrollment, substantial improvements were observed: influenza, 89.2%; PCV13, 74.5%; PPV23, 67.0%; herpes zoster, 75.4%; and COVID-19 primary cycle, 96.8%. Coverage for catch-up vaccines also improved (e.g., HBV went from 1.9% to 44.2%). However, uptake of COVID-19 booster doses during the study period remained low (15.6%). No significant differences emerged by sex or treatment subgroup. <b>Conclusions</b>: A structured, collaborative care pathway between gastroenterologists and public health specialists significantly improved vaccination coverage among IBD patients. Despite gains, gaps persist in COVID-19 booster uptake and catch-up vaccinations. Integration of vaccination services into routine IBD management is essential to enhance protection in this high-risk population.</p>","PeriodicalId":23634,"journal":{"name":"Vaccines","volume":"13 9","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12474384/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145179025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differences in Glycoproteins and the Potential for Early Protection Using LAIV Based on Drift Variants of the A/H1N1pdm09 Influenza Virus.","authors":"Yulia Desheva, Irina Mayorova, Andrey Rekstin, Daniil Sokolovsky, Polina Kudar, Nina Kopylova, Danila Guzenkov, Darya Petrachkova, Andrey Mamontov, Andrey Trullioff, Irina Kiseleva","doi":"10.3390/vaccines13090966","DOIUrl":"10.3390/vaccines13090966","url":null,"abstract":"<p><strong>Background/objectives: </strong>Antigenic drift of influenza A(H1N1pdm09) viruses has led to periodic replacement of vaccine strains. Understanding how structural differences in glycoproteins influence immune protection is crucial for improving vaccine effectiveness.</p><p><strong>Methods: </strong>We conducted a structural analysis of the hemagglutinin (HA) and neuraminidase (NA) glycoproteins from drifted A(H1N1)pdm09 strains: A/South Africa/3626/2008 and A/Guangdong-Maonan/SWL1/2020, as well as their cold-adapted live attenuated vaccine (LAIV) reassortant strains (A/17/South Africa/2013/01(H1N1)pdm09 and A/17/Guangdong-Maonan/2019/211(H1N1)pdm09). We compared their replication in chicken embryo and mammalian cell culture, assessed type I interferon induction, and evaluated post-vaccine protection in mice after homologous and heterogeneous viral challenges.</p><p><strong>Results: </strong>The two vaccine strains had distinct glycosylation patterns for HA and NA. However, they had similar replication capacity in embryonated egg and mammalian cells. In the mouse respiratory tract, both strains replicated similarly. A/17/South Africa/2013/01(H1N1)pdm09 induced significantly higher levels of IFN-α and Mx1 in vitro, and it elicited earlier IgM and IgG response after vaccination in mice. At day 6 after immunization, it provided 70% protection from homologous challenge. A/17/Guangdong-Maonan/2019/211(H1N1)pdm09 did not prevent death, but it reduced viral titer in the lungs. Interestingly, A/17/South Africa/2013/01(H1N1)pdm09 provided full protection from heterologous H5N1 challenge, while A/17/Guangdong-Maonan/2019/211(H1N1)pdm09) only provided partial protection.</p><p><strong>Conclusions: </strong>Differences in HA and NA glycans among A(H1N1)pdm09 strains may influence innate and adaptive immunity, as well as cross-protection. These findings emphasize the importance of glycoprotein structure when selecting vaccine candidates for optimal homologous and cross-protection against influenza.</p>","PeriodicalId":23634,"journal":{"name":"Vaccines","volume":"13 9","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12474416/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145178746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cord Blood RSV-Neutralizing Antibodies and Risk of Hospitalization for RSV-Associated Acute Respiratory Infection in Vietnamese Children: A Case-Cohort Study.","authors":"Michiko Toizumi, Yutaro Yamagata, Hien Anh Thi Nguyen, Hirono Otomaru, Hoang Huy Le, Hiroyuki Moriuchi, Jean-Francois Eleouet, Marie-Anne Rameix-Welti, Makoto Takeda, Hung Thai Do, Lay-Myint Yoshida","doi":"10.3390/vaccines13090963","DOIUrl":"10.3390/vaccines13090963","url":null,"abstract":"<p><strong>Background: </strong>Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections in children, particularly severe during infancy. Maternal RSV-specific neutralizing antibodies (nAbs), transferred via the placenta, may provide protection in early infancy, but the extent and duration of protection remain uncertain.</p><p><strong>Objective: </strong>We investigated the association between cord blood RSV-A nAb levels and the risk of hospitalization due to RSV-associated acute respiratory infection (RSV-ARI) by 24 months of age.</p><p><strong>Methods: </strong>We conducted a case-cohort study nested within a birth cohort in Nha Trang, Vietnam. From the full cohort (<i>n</i> = 1977), a random subcohort of 392 infants and all 66 infants hospitalized for RSV-ARI by age 24 months were included for RSV-A nAb testing. RSV-A nAb titers at birth were categorized into three groups in the subcohort (low: lowest quartile; middle; interquartile; high: highest quartile). Weighted Cox proportional hazards regression was used to estimate hazard ratios (HRs) for RSV-ARI hospitalization.</p><p><strong>Results: </strong>The incidence of RSV-ARI hospitalization was 17.92 per 1000 person-years by 24 months, and 25.40 per 1000 person-years among infants aged <12 months. Among infants aged <6 months, those in the low nAb group had a significantly higher risk of hospitalization compared to the middle nAb group (adjusted HR: 4.05; 95% CI: 1.51-10.89). Maternal anemia was consistently associated with increased risk.</p><p><strong>Conclusions: </strong>Lower RSV-nAb titers at birth were associated with an increased risk of RSV-ARI hospitalization during early infancy. These findings support the importance of maternal immunization strategies to enhance infant protection against RSV.</p>","PeriodicalId":23634,"journal":{"name":"Vaccines","volume":"13 9","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12474007/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145178941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Case Report: A Multi-Peptide Vaccine Targeting Individual Somatic Mutations Induces Tumor Infiltration of Neoantigen-Specific T Cells in a Patient with Metastatic Colorectal Cancer.","authors":"Armin Rabsteyn, Henning Zelba, Borong Shao, Lisa Oenning, Christina Kyzirakos, Simone Kayser, Tabea Riedlinger, Johannes Harter, Magdalena Feldhahn, Dirk Hadaschik, Florian Battke, Veit Scheble, Alfred Königsrainer, Saskia Biskup","doi":"10.3390/vaccines13090960","DOIUrl":"10.3390/vaccines13090960","url":null,"abstract":"<p><strong>Background/objectives: </strong>Fully personalized peptide vaccines targeting tumor-specific mutations are a promising treatment option for patients in an adjuvant but also advanced/metastatic disease situation in addition to non-personalized standard therapies. Here, we report a patient's case with advanced metastatic colorectal cancer (mCRC) who was treated with a neoantigen-derived multi-peptide vaccine in addition to standard of care.</p><p><strong>Methods: </strong>Tumor-specific mutations were identified by whole exome and transcriptome sequencing. An individualized peptide vaccine was designed using an in-house developed epitope prediction and vaccine design platform. In this case, the vaccine consisted of 20 peptides targeting 18 distinct mutations. The vaccine was administered according to a prime-boost scheme for a total of 12 vaccinations. Vaccine immunogenicity was determined by stimulation of patient T cells with vaccinated peptides and subsequent intracellular cytokine staining (ICS). Tumor-infiltrating lymphocytes (TIL) were analyzed by ICS and T cell receptor beta chain (TCRβ) sequencing.</p><p><strong>Results: </strong>The patient survived for 41 months since initial diagnosis despite continuous disease progression under all therapeutic interventions. The vaccination induced multiple neoantigen-specific T cell responses in the patient without notable side effects. Two liver metastases were resected five months after the start of vaccination, and TIL were extracted and cultured. Analysis of TIL cultures revealed tumor infiltration by vaccine-induced neoantigen-specific T cells in only one of the metastases. TCRβ sequencing of neoantigen-specific T cells and tumor tissues supported this finding. Vaccine-targeted variants were reduced or absent in the metastasis with vaccine-specific T cell infiltration.</p><p><strong>Conclusions: </strong>This case demonstrates immunogenicity of a neoantigen-derived peptide vaccine and highlights tumor-infiltrating capabilities and potential cytotoxicity of vaccine-induced T cells in mCRC.</p>","PeriodicalId":23634,"journal":{"name":"Vaccines","volume":"13 9","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12474295/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145178872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antibody Responses to SARS-CoV-2 and Common HCoVs in Hemodialysis Patients and Transplant Recipients: Data from the Dominican Republic.","authors":"Lisette Alcantara Sanchez, Eloy Alvarez Guerra, Dongmei Li, Samantha M King, Shannon P Hilchey, Qian Zhou, Stephen Dewhurst, Kevin Fiscella, Martin S Zand","doi":"10.3390/vaccines13090965","DOIUrl":"10.3390/vaccines13090965","url":null,"abstract":"<p><p><b>Background:</b> Vaccination against SARS-CoV-2 has been pivotal in controlling the COVID-19 pandemic. However, understanding vaccine-induced immunity in immunocompromised individuals remains critical, particularly how prior exposure to other coronaviruses modulates immune responses. The influence of previous infections with endemic human coronaviruses (HCoVs), such as OC43, on SARS-CoV-2 immunity is not fully understood. This study evaluates antibody responses to COVID-19 vaccination in hemodialysis patients (HD), transplant recipients (TR), and healthy controls (CO), accounting for prior SARS-CoV-2 infection and baseline human coronavirus (HCoV) reactivity. <b>Methods:</b> We obtained longitudinal antibody measurements from 70 subjects (CO: <i>n</i> = 33; HD: <i>n</i> = 13; TR: <i>n</i> = 24) and assessed antibody kinetics across multiple post-vaccination time points using multivariate linear mixed modeling (MLMM). <b>Results:</b> Limited but measurable cross-reactivity was observed between SARS-CoV-2 and endemic HCoVs, particularly the β-coronavirus OC43. Pre-existing immunity in healthy individuals modestly enhanced vaccine-induced anti-spike (S) IgG responses, supported by post-vaccination increases in SARS-CoV-2 IgG. Prior SARS-CoV-2 infection significantly influenced anti-S and nucleocapsid (N) IgG responses but had limited impact on endemic HCoVs responses. Vaccine type and immune status significantly affected antibody kinetics. mRNA vaccination (BNT162b2) elicited stronger and more durable SARS-CoV-2 anti-S IgG responses than the inactivated CoronaVac vaccine, especially in immunocompetent individuals. Immunocompromised groups showed delayed or attenuated responses, with modest anti-S IgG cross-reactive boosting. Elevated anti-N IgG in CoronaVac recipients raised questions about its origin-infection or vaccine effects. MLMM identified key immunological and clinical predictors of antibody responses, emphasizing the critical role of host immune history. <b>Conclusions:</b> These findings highlight a constrained but meaningful role for HCoV cross-reactivity in SARS-CoV-2 immunity and vaccine responsiveness, underscore the need for infection markers unaffected by vaccination, and support development of broadly protective pan-coronavirus vaccines and tailored strategies for at-risk populations.</p>","PeriodicalId":23634,"journal":{"name":"Vaccines","volume":"13 9","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12474128/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145178811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}