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Search Results (569)

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Keywords = co-administration of vaccines

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17 pages, 382 KB  
Article
COVID-19 Vaccination, Hospitalization Rates, and Mortality Differ Between People with Diagnosed Immune Mediated Inflammatory Disease and the General Population: A Population-Based Study
by Carol A. Hitchon, Carole Taylor, Charles N. Bernstein, Christine A. Peschken, Diane Lacaille, Gilaad G. Kaplan, Jessica Widdifield and Ruth Ann Marrie
Vaccines 2025, 13(11), 1130; https://doi.org/10.3390/vaccines13111130 - 2 Nov 2025
Viewed by 520
Abstract
Background: Vaccination reduces Coronavirus disease-19 (COVID-19) infection severity. We evaluated COVID-19 vaccine uptake and effectiveness in people with immune mediated inflammatory diseases (pIMIDs) versus the general population. Methods: Using population-based administrative health records, we identified cohorts between 2004 and 2022 with an IMID [...] Read more.
Background: Vaccination reduces Coronavirus disease-19 (COVID-19) infection severity. We evaluated COVID-19 vaccine uptake and effectiveness in people with immune mediated inflammatory diseases (pIMIDs) versus the general population. Methods: Using population-based administrative health records, we identified cohorts between 2004 and 2022 with an IMID (rheumatoid arthritis n = 10,405, systemic autoimmune rheumatic disease n = 5888, inflammatory bowel disease n = 7911, multiple sclerosis n = 3665, psoriasis n = 23,948) who were matched (1:5) by age, sex, and region to general population comparators (n = 243,490) without these IMIDs. Between 1 January 2021 and 31 March 2022, rates of COVID-19 vaccine administration, hospitalizations with COVID-19 (Hosp-C), and all-cause mortality were assessed amongst pIMIDs and comparators using multivariable models. Results: More pIMIDs were vaccinated than comparators (87.3% vs. 84.7%, p < 0.0001). IMID diagnosis, increasing age, female sex, higher socioeconomic status, urban residence, immunotherapy use, and comorbidities were associated with increased odds of receiving at least two vaccine doses. pIMIDs had higher rates of Hosp-C (79 per 100,000, 95% confidence interval (CI) 77.8–80.2) than comparators (51 per 100,000, 95% CI 50.5–51.3; rate ratio 1.55; 95% CI 1.53, 1.58) and greater mortality [pIMID 1758 deaths, 3.61%; comparators (6346 deaths, 2.61%), RR 1.39 95% CI 1.32, 1.46)]. In multivariable analyses, vaccinated status was associated with less Hosp-C (OR 0.27, CI 0.23, 0.32) and death (HR 0.27 CI 0.24, 0.29); the association did not differ between IMID and comparator groups. Conclusions: Although COVID-19 vaccination reduced the risk of Hosp-C and death in both pIMIDs and comparators, pIMIDs remained at higher risk for both. Since SARS-CoV-2 is now endemic, these findings may inform ongoing vaccination recommendations. Full article
(This article belongs to the Special Issue Immunization of Immunosuppressed Patients)
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20 pages, 1726 KB  
Article
Heterologous SARS-CoV-2 Buccal Immunization with Oral Dissolving Films Generated a Strong Systemic and Mucosal Immunity in a Murine Model
by Tanisha Manoj Arte, Smital Patil, Emmanuel Adediran, Mahek Gulani, Amarae Ferguson, Sarthak Shah, Priyal Bagwe, Susu M. Zughaier and Martin J. D’Souza
Vaccines 2025, 13(11), 1105; https://doi.org/10.3390/vaccines13111105 - 29 Oct 2025
Viewed by 378
Abstract
Background: In response to the emergence of immune-evasive variants of SARS-CoV-2, this study explores a novel heterologous vaccination strategy using a microparticulate formulation approach that is delivered via oral dissolving film (ODF) formulations into the buccal cavity. Heterologous administration has the potential to [...] Read more.
Background: In response to the emergence of immune-evasive variants of SARS-CoV-2, this study explores a novel heterologous vaccination strategy using a microparticulate formulation approach that is delivered via oral dissolving film (ODF) formulations into the buccal cavity. Heterologous administration has the potential to generate cross-reactive antibodies, which can be especially beneficial against viruses with ever-mutating variants. Moreover, the microparticulate oral dissolving film-based vaccine approach is a non-invasive vaccine delivery platform. Methods: The vaccine design incorporated whole inactivated Delta and Omicron variants of the virus, administered at prime and booster doses, respectively, effectively encapsulated in a Poly(lactic-co-glycolic) acid (PLGA) polymer matrix, and adjuvanted with Alum to enhance immune activation. Following vaccination, serum, mucosal, and tissue samples were analyzed to evaluate humoral and cellular immune responses against the model antigen, as well as other variants such as Alpha and Beta variants, to understand the cross-reactive response. Result: In vitro evaluations confirmed the vaccine’s safety and its ability to stimulate immune responses. On administering microparticulate oral dissolving films to mice, whole inactivated delta and omicron variant-specific antibodies were observed in serum samples along with neutralizing titers in terminal week. The formulated vaccine showed significant secretory IgA antibody levels in mucosal samples. Moreover, CD4+ and CD8a cellular responses were observed in tissue samples of spleen and lymph nodes, along with antibodies (IgG, IgA, and IgM) detected in lung supernatant samples. Humoral and cellular cross-reactive antibodies were observed in the samples. Conclusions: This approach offers a promising platform for developing next-generation vaccines capable of inducing broad immunity. Full article
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12 pages, 451 KB  
Article
Immunogenicity and Safety of Sabin Strain Inactivated Poliovirus Vaccine Booster Dose Administered Separately or Concomitantly with Inactivated Hepatitis A Vaccine or Measles–Mumps–Rubella Combined Attenuated Live Vaccine: An Open-Labelled, Randomized, Controlled, Phase 4 Clinical Trial
by Jialei Hu, Weixiao Han, Kai Chu, Hengzhen Zhang, Ling Tuo, Xiaoqian Duan, Jun Li, Fang Yuan, Chunfang Luan, Hongxing Pan and Peng Jiao
Vaccines 2025, 13(11), 1087; https://doi.org/10.3390/vaccines13111087 - 23 Oct 2025
Viewed by 418
Abstract
Objectives: To determine whether a Sabin strain inactivated poliovirus booster (sIPV) given concomitantly (same day, different sites) with MMRV or inactivated hepatitis A vaccine (HepA) is non-inferior in immunogenicity and comparable in safety to separate administration at the 18-month visit. Methods: Open-label, randomized [...] Read more.
Objectives: To determine whether a Sabin strain inactivated poliovirus booster (sIPV) given concomitantly (same day, different sites) with MMRV or inactivated hepatitis A vaccine (HepA) is non-inferior in immunogenicity and comparable in safety to separate administration at the 18-month visit. Methods: Open-label, randomized Phase IV trial in healthy children (18~22 months), allocated 2:2:2:1:1 to sIPV&MMRV, sIPV&HepA, sIPV-only, MMRV-only, or HepA-only. Primary endpoints were Day-30 seroconversion rates (SCRs) for poliovirus types 1–3 (sIPV arms) and for HepA (HepA arms). Results: Of 892 screened, 889 were randomized; baseline characteristics were balanced. By Day 30, seroprotection was 100% for PV types 1–3 in all sIPV-containing arms. SCRs were high and similar across concomitant vs. separate administration; all pairwise SCR differences met non-inferiority (−10% margin). Adjusted post-vaccination GMTs were comparable across serotypes. For HepA, Day-30 SPoR was 99.3% vs. 100.0%, and adjusted GMC was 412.2 vs. 465.9 (p = 0.2224). For MMRV, Day-30 SPoR was 100% in both groups with similar adjusted GMCs. Within 30 days, overall adverse reactions were 14.5%/17.4%/16.3%/7.3%/10.8% (sIPV&MMRV/sIPV&HepA/sIPV-only/MMRV-only/HepA-only), mostly mild to moderate; no vaccine-related SAEs (NCT06442449). Conclusions: Same-day sIPV co-administration with MMRV or HepA was non-inferior and well tolerated, supporting programmatic adoption. Full article
(This article belongs to the Section Vaccine Advancement, Efficacy and Safety)
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15 pages, 1103 KB  
Article
A Novel Flow Cytometry Array for High Throughput Detection of SARS-CoV-2 Antibodies
by Benyue Zhang, Zhuo Zhang, Yichao Zhao, Jingqiao Lu, Jianmin Fang, Brianne Petritis, Kelly Whittaker, Rani Huang and Ruo-Pan Huang
Vaccines 2025, 13(10), 1063; https://doi.org/10.3390/vaccines13101063 - 17 Oct 2025
Viewed by 561
Abstract
Background/Objectives: Although the U.S. Food and Drug Administration (FDA) has approved one antiviral treatment and authorized others for emergency use, there is no fully effective antiviral therapy for coronavirus disease 2019 (COVID-19), which is caused by the severe acute respiratory syndrome coronavirus 2 [...] Read more.
Background/Objectives: Although the U.S. Food and Drug Administration (FDA) has approved one antiviral treatment and authorized others for emergency use, there is no fully effective antiviral therapy for coronavirus disease 2019 (COVID-19), which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Assays detecting virus-specific immunoglobulins (Ig) or nucleic acids in large-scale epidemiological, vaccine, and drug development studies remain limited due to high costs, reagent accessibility, and cumbersome protocols. Methods: A multiplex bead-based assay was developed to simultaneously detect human IgM, IgG, and IgA antibodies against the SARS-CoV-2 spike receptor binding domain (RBD) in serum using flow cytometry. Assay performance was evaluated for sensitivity, specificity, reproducibility, and cross-reactivity and compared to another immunoassay platform. Results: The assay enabled simultaneous measurement of three antibody isotypes across 624 samples within 2 h. Intra-plate coefficients of variation (CVs) ranged from 3.16 to 6.71%, and inter-plate CVs ranged from 3.33 to 5.49%, demonstrating high reproducibility. The platform also quantified background noise from nonspecific binding, facilitating straightforward data interpretation. Conclusions: This novel, flexible multiplex bead-based assay utilizing a well-established platform provides a rapid and reproducible approach for detecting SARS-CoV-2-specific antibodies. Its high throughput capacity and low variability make it well suited for large-scale epidemiological, vaccine, and therapeutic studies. The platform’s adaptability further supports application to other infectious diseases, offering an ideal tool for broad immunological surveillance. Full article
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12 pages, 1030 KB  
Article
Safety Evaluation of Tetanus, Diphtheria, and Acellular Pertussis Vaccine (Tdap) During Pregnancy Among Vietnamese Women
by Hien Minh Nguyen, Nhat Thang Tran, Quoc Huy Pham and Huu Nghia Cao
Vaccines 2025, 13(10), 1036; https://doi.org/10.3390/vaccines13101036 - 8 Oct 2025
Viewed by 1025
Abstract
Background: In Vietnam, the Ministry of Health recently approved the use of Tdap vaccines—Boostrix (2022) and Adacel (2024)—for administration during pregnancy, aiming to provide passive antibody transfer to protect newborns against pertussis and tetanus from birth. However, uptake remains low, largely because Tdap [...] Read more.
Background: In Vietnam, the Ministry of Health recently approved the use of Tdap vaccines—Boostrix (2022) and Adacel (2024)—for administration during pregnancy, aiming to provide passive antibody transfer to protect newborns against pertussis and tetanus from birth. However, uptake remains low, largely because Tdap is not included in the National Expanded Program on Immunization, vaccine hesitancy persists among obstetricians, and local safety data in pregnancy are limited. Methods: We conducted a prospective cohort study from September 2023 to September 2024 involving 485 pregnant women between 27 and 36 weeks of gestation at two major hospitals in Ho Chi Minh City: University Medical Center and Gia Dinh People’s Hospital. Participants received either Tdap or monovalent tetanus toxoid vaccine (TT) as a comparator. Results: Among women in the Tdap group, 49.8% reported at least one adverse event following immunization (AEFI). Local reactions were the most frequent, primarily injection-site pain (43.8%). Fatigue (12.8%) was the most common systemic reaction, followed by headache (3.9%). Grade 3 AEFIs occurred in 5% of the Tdap group and included extensive local reactions (erythema or swelling > 3 cm), high-grade fever (≥40 °C), and severe fatigue interfering with daily activities or requiring hospitalization. Women receiving Tdap had 1.52-fold higher injection-site pain compared with those receiving TT (95% CI: 0.060–0.782). Importantly, co-administration of Tdap with inactivated quadrivalent influenza vaccine (IIV4) did not increase the risk of AEFIs. Furthermore, no evidence was found that Tdap vaccination adversely affected the course of pre-existing maternal comorbidities, which remained stable throughout pregnancy. Conclusions: This first large-scale Vietnamese cohort provides reassuring evidence on the safety of Tdap vaccination during pregnancy. These findings support broader implementation of maternal Tdap immunization, including concomitant administration with IIV4, to protect both mothers and infants. Full article
(This article belongs to the Special Issue Vaccines for the Vulnerable Population)
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26 pages, 6802 KB  
Article
Multifunctional Polymer-Modified P-CaO2@Au@OVA@Cu@DHPs Nanoparticles Enhance SARS-CoV-2 mRNA Vaccine-Induced Immunity via the cGAS–STING Signaling Pathway
by Yanle Zhi, Shengchao Wang, Haibo Zhang, Guimin Xue and Zhiqiang Zhang
Polymers 2025, 17(19), 2636; https://doi.org/10.3390/polym17192636 - 30 Sep 2025
Viewed by 453
Abstract
The success of mRNA-based SARS-CoV-2 vaccines has been confirmed in both preclinical and clinical settings. However, the development of safe and efficient mRNA vaccine delivery platforms remains challenging. In this report, PBAE-G-B-SS-modified CaO2 nanofibers and Au@OVA@Cu@Dendrobium huoshanense polysaccharides were employed to establish [...] Read more.
The success of mRNA-based SARS-CoV-2 vaccines has been confirmed in both preclinical and clinical settings. However, the development of safe and efficient mRNA vaccine delivery platforms remains challenging. In this report, PBAE-G-B-SS-modified CaO2 nanofibers and Au@OVA@Cu@Dendrobium huoshanense polysaccharides were employed to establish novel self-assembling polymeric micelles (CaO2@Au@OVA@Cu@DHPs) capable of serving as both an adjuvant and a delivery system for mRNA vaccines. In vitro, CaO2@Au@OVA@Cu@DHPs nanoparticles (NPs) were conducive to effective macrophage antigen uptake and efficient antigen processing. In vivo, P-CaO2@Au@OVA@Cu@DHPs NP administration was associated with a reduction in the ovalbumin (OVA) release rate that was conducive to the sustained induction of long-term immunity and to the production of higher levels of different IgG subtypes, suggesting that these effects were attributable to enhanced antigen uptake by antigen-presenting cells. Overall, these present data highlight the promise of these P-CaO2@Au@OVA@Cu@DHPs NPs as an effective and safe platform amenable to vaccine delivery through their ability to provide robust adjuvant activity and sustained antigen release capable of eliciting long-term immunological memory while potentiating humoral and cellular immune responses. Full article
(This article belongs to the Section Polymer Applications)
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26 pages, 2093 KB  
Article
Preclinical Evaluation of the Efficacy of α-Difluoromethylornithine and Sulindac Against SARS-CoV-2 Infection
by Natalia A. Ignatenko, Hien T. Trinh, April M. Wagner, Eugene W. Gerner, Christian Bime, Chiu-Hsieh Hsu and David G. Besselsen
Viruses 2025, 17(10), 1306; https://doi.org/10.3390/v17101306 - 26 Sep 2025
Viewed by 679
Abstract
Despite numerous research efforts and several effective vaccines and therapies developed against coronavirus disease 2019 (COVID-19), drug repurposing remains an attractive alternative approach for treatment of SARS-CoV-2 variants and other viral infections that may emerge in the future. Cellular polyamines support viral propagation [...] Read more.
Despite numerous research efforts and several effective vaccines and therapies developed against coronavirus disease 2019 (COVID-19), drug repurposing remains an attractive alternative approach for treatment of SARS-CoV-2 variants and other viral infections that may emerge in the future. Cellular polyamines support viral propagation and tumor growth. Here we tested the antiviral activity of two polyamine metabolism-targeting drugs, an irreversible inhibitor of polyamine biosynthesis, α-difluoromethylornithine (DFMO), and a non-steroidal anti-inflammatory drug (NSAID), Sulindac, which have been previously evaluated for colon cancer chemoprevention. The drugs were tested as single agents and in combination in the human Calu-3 lung adenocarcinoma and Caco-2 colon adenocarcinoma cell lines and the K18-hACE2 transgenic mouse model of severe COVID-19. In the infected human cell lines, the DFMO/Sulindac combination significantly suppressed SARS-CoV-2 N1 Nucleocapsid mRNA by interacting synergistically when cells were pretreated with drugs and additively when treatment was applied to the infected cells. The Sulindac alone and DFMO/Sulindac combination treatments also suppressed the expression of the viral Spike protein and the host angiotensin-converting enzyme 2 (ACE2). In K18-hACE2 mice, the antiviral activity of DFMO and Sulindac as single agents and in combination was tested as prophylaxis (drug supplementation started 7 days before infection) or as treatment (drug supplementation started 24 h post-infection) at the doses equivalent to patient chemoprevention trials (835 ppm DFMO and 167 ppm Sulindac). The drugs’ antiviral activity in vivo was evaluated by measuring the clinical (survival rates and clinical scores), viral (viral load and virus infectivity), and biochemical (plasma polyamine, Sulindac, and Sulindac metabolite levels) endpoints. Prophylaxis with DFMO and Sulindac as single agents significantly increased survival rates in the young male mice (p = 0.01 and p = 0.027, respectively), and the combination was effective in the aged male mice (p = 0.042). Young female mice benefited the most from the prophylaxis with Sulindac alone (p = 0.001) and the DFMO/Sulindac combination (p = 0.018), while aged female mice did not benefit significantly from any intervention. Treatment of SARS-CoV-2-infected animals with DFMO or/and Sulindac did not significantly improve their survival rates. Overall, our studies demonstrated that DFMO and Sulindac administration as the prophylaxis regimen provided strong protection against the lethal outcome of SARS-CoV-2 infection and that male mice benefited more from the polyamine-targeted antiviral treatment than female mice. Our findings underscore the importance of evaluation of the antiviral activity of the drugs in the context of sex and age. Full article
(This article belongs to the Section Coronaviruses)
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18 pages, 11924 KB  
Article
Next-Generation Sequencing Reveals Field Strain Dynamics and PRRSV-2 Clearance in Gilts When Using Tylvalosin During MLV Vaccination
by Weixin Wu, Xiang Gao, Junfeng Gao, Zhi Lai, Xiaohong Deng, Junnan Zhang, Qiongqiong Zhou and Lei Zhou
Vaccines 2025, 13(10), 1007; https://doi.org/10.3390/vaccines13101007 - 25 Sep 2025
Viewed by 520
Abstract
Background: Porcine reproductive and respiratory syndrome virus (PRRSV) causes significant economic losses for the global swine industry. Gilt immunization using modified live virus (MLV) vaccines is crucial for herd stability, but it is complicated by frequent mixed infections of PRRSV strains on farm. [...] Read more.
Background: Porcine reproductive and respiratory syndrome virus (PRRSV) causes significant economic losses for the global swine industry. Gilt immunization using modified live virus (MLV) vaccines is crucial for herd stability, but it is complicated by frequent mixed infections of PRRSV strains on farm. This study monitored the administration of tylvalosin during a PRRSV-2 MLV (TJM) immunization program, focusing on viral dynamics and immune responses in gilts naturally exposed to co-circulating classical (GD240101) and highly pathogenic like (HP-PRRSV-like, GD240102) PRRSV strains. Methods: The animal study was approved by the Laboratory Animal Ethical Committee of China Agricultural University. One hundred gilts were randomized into control and tylvalosin groups (n = 50/group). All received the TJM MLV vaccination. The tylvalosin group received tylvalosin tartrate premix cyclically in-feed for three cycles. Serum and saliva samples were collected periodically. PRRSV RNA (RT-qPCR) and specific antibodies (ELISA) were assessed. Viral population dynamics (relative abundance, mutation, recombination of TJM, GD240101, and GD240102) were monitored via next-generation sequencing (NGS) on a pooled PRRSV-positive sample. Results: In this field trial where tylvalosin was used, a shorter duration of PRRSV viremia and saliva shedding was observed to compare with controls. NGS analysis showed accelerated vaccine strain (TJM) clearance in the tylvalosin group (by week 3 vs. week 9 in control). Field strain dynamics were also altered, showing a faster decline in the tylvalosin group. Antibody response uniformity was altered, with lower coefficient of variation (CV) for PRRSV and CSFV observed following tylvalosin usage. Conclusions: In gilts receiving tylvalosin for the management of bacterial pathogens during a PRRSV MLV immunization program, it was associated with accelerated viral clearance and enhanced systemic immune response uniformity under mixed-infection field conditions. NGS provides invaluable data for dissecting these complex viral dynamics. Crucially, these findings describe a biological drug–host–virus interaction and should not be interpreted as an endorsement for the prophylactic use of antimicrobials. In alignment with global antimicrobial stewardship principles, tylvalosin should be reserved for the therapeutic treatment of diagnosed bacterial diseases to mitigate the risk of promoting resistance. Full article
(This article belongs to the Section Veterinary Vaccines)
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16 pages, 1928 KB  
Article
Dual-Function Adjuvant Cyclosporin A: Enhancing RSV-Specific Humoral Immunity via Treg-Driven B-Cell Activation
by Chaofan Li, Yiwei Zhong, Shuren Zhang, Caixia Su, Gan Zhao and Bin Wang
Vaccines 2025, 13(10), 997; https://doi.org/10.3390/vaccines13100997 - 23 Sep 2025
Viewed by 533
Abstract
Background: Respiratory syncytial virus (RSV) remains a leading cause of respiratory illness globally, with limited vaccine options, particularly for infants and high-risk populations. This study investigates Cyclosporin A (CsA), traditionally an immunosuppressant, as a novel adjuvant to enhance RSV-specific immunity. Methods: BALB/c mice [...] Read more.
Background: Respiratory syncytial virus (RSV) remains a leading cause of respiratory illness globally, with limited vaccine options, particularly for infants and high-risk populations. This study investigates Cyclosporin A (CsA), traditionally an immunosuppressant, as a novel adjuvant to enhance RSV-specific immunity. Methods: BALB/c mice were subcutaneously immunized with RSV G protein co-administered with varying Cyclosporin A doses, challenged intranasally with RSV, and analyzed for RSV-specific humoral immunity and mechanistic Treg-dependent B-cell responses. Results: We demonstrate that co-administration of CsA with the RSV G protein (G+CsA) dose-dependently boosts RSV-specific IgG and neutralizing antibodies, with selective augmentation of IgG1 and IgG2 subclasses. Mechanistically, G+CsA induces regulatory T cells (Tregs) expressing CD40L and IL-10, which directly promote B-cell activation, proliferation, and plasma cell differentiation. Depletion of Tregs or neutralization of IL-10/CD40L abrogated antibody production, confirming these pathways as critical mediators. Notably, G+CsA-induced Tregs adopt a helper phenotype distinct from conventional Tregs, balancing immune enhancement and homeostasis. Conclusions: CsA demonstrates dual adjuvant properties by enhancing RSV-specific neutralizing IgG titers through Treg-driven B-cell activation, offering a potential strategy to optimize vaccine-induced humoral immunity. Full article
(This article belongs to the Special Issue Respiratory Syncytial Virus (RSV) Vaccine)
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17 pages, 1030 KB  
Review
Next-Generation mRNA Vaccines in Melanoma: Advances in Delivery and Combination Strategies
by Stefano Zoroddu and Luigi Bagella
Cells 2025, 14(18), 1476; https://doi.org/10.3390/cells14181476 - 22 Sep 2025
Cited by 1 | Viewed by 3207
Abstract
Messenger RNA (mRNA) vaccines have redefined cancer immunotherapy, offering unparalleled flexibility to encode tumor-specific antigens and to be adapted to individual mutational landscapes. Melanoma, with its high mutational burden and responsiveness to immune checkpoint blockade, has become the leading model for translating these [...] Read more.
Messenger RNA (mRNA) vaccines have redefined cancer immunotherapy, offering unparalleled flexibility to encode tumor-specific antigens and to be adapted to individual mutational landscapes. Melanoma, with its high mutational burden and responsiveness to immune checkpoint blockade, has become the leading model for translating these advances into clinical benefit. Recent innovations in delivery—ranging from lipid nanoparticles and polymeric carriers to biomimetic hybrids and intratumoral administration—are dismantling long-standing barriers of stability, targeting, and immunogenicity. Clinical milestones, including the randomized phase IIb KEYNOTE-942, show that adding the personalized neoantigen vaccine mRNA-4157 (V940) to pembrolizumab prolonged recurrence-free survival versus pembrolizumab alone (HR 0.561, 95% CI 0.309–1.017; 18-month RFS 79% vs. 62%), with the ASCO 3-year update reporting 2.5-year RFS 74.8% vs. 55.6% and sustained distant metastasis-free survival benefit in resected high-risk melanoma. Parallel preclinical studies highlight the potential of multifunctional platforms co-delivering cytokines or innate agonists to reshape the tumor microenvironment and achieve durable systemic immunity. As artificial intelligence drives epitope selection and modular manufacturing accelerates personalization, mRNA vaccines may have the potential to transition from adjuncts to main therapies in melanoma and beyond. Full article
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17 pages, 1083 KB  
Article
Immunogenicity and Safety Results of a Randomized, Three-Arm, Phase IV Clinical Trial of Concomitant Administration of Typhoid Vi Conjugate Vaccine with Measles and Rubella Vaccine in Healthy Infants
by Songa Narayana Rao, Deepali Ambike, Mahantesh Patil, Sanjay Vasant Mankar, Nishant Verma, Neeta Hanumante, Lisa Sarangi, Monjori Mitra, Godatwar Preeti, Bhaskar Jedhe Deshmukh, Girish Nanoti, Mohammad Moonis Akbar Faridi, Pavankumar Daultani, Ravindra Mittal, Kapil Maithal, Kevinkumar Kansagra, Deven V. Parmar, Radhakrishnan Kunnathamman, Manickam Elaiyaraja, Trayambak Dutta, Manish Mahajan and Samir Desaiadd Show full author list remove Hide full author list
Viruses 2025, 17(9), 1237; https://doi.org/10.3390/v17091237 - 12 Sep 2025
Viewed by 743
Abstract
Typhoid fever, measles, and rubella continue to contribute significantly to childhood morbidity and mortality in India. In line with WHO recommendations for co-administration of Typhoid Conjugate Vaccine (TCV) and measles–rubella (MR) vaccine at 9 months of age, this phase IV, randomized, open-label, multicenter [...] Read more.
Typhoid fever, measles, and rubella continue to contribute significantly to childhood morbidity and mortality in India. In line with WHO recommendations for co-administration of Typhoid Conjugate Vaccine (TCV) and measles–rubella (MR) vaccine at 9 months of age, this phase IV, randomized, open-label, multicenter clinical trial was conducted to assess their immunological compatibility and safety when administered concomitantly. A total of 900 healthy Indian infants aged 9–10 months were randomized into three groups: Group A received TCV and MR vaccine concomitantly; Group B received MR on Day 0 and TCV on Day 28; Group C received TCV on Day 0 and MR on Day 28. Subjects were followed for 6 months after concomitant/last vaccination. Seroconversion rates (SC) in Groups A/B/C at Day 28 were 90.2%/75.3%/89.5% for anti-Vi; 80.4%/75.2%/77.7% for anti-measles, and 87.7%/84.0%/85.2% for anti-rubella antibodies. By study end, SC for anti-Vi was 87.1%/71.6%/83.0%, while SC for anti-measles and anti-rubella reached ~90% and ≥98%, respectively, across all groups. Geometric mean titers increased significantly for all antigens, with no evidence of immunological interference. Safety assessments showed adverse events in 23.9%/32.0%/32.7% participants in Group A/B/C. Most adverse events were mild, and only one serious adverse event was reported. These findings support the co-administration of TCV and MR vaccine as a safe and effective strategy. Full article
(This article belongs to the Section Viral Immunology, Vaccines, and Antivirals)
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11 pages, 551 KB  
Article
Humoral Response to the Third Dose of SARS-CoV-2 Vaccine Among Dialysis Patients: A Breakthrough Infection Case–Control Study
by Francesca Colavita, Concetta Castilletti, Giulia Matusali, Silvia Accordini, Salvatore De Masi, Roberto Da Cas, Natasha Gianesini, Giovanni Baglio, Massimo Francalancia, Giuseppe Traversa, Flavia Chiarotti, Silvia Meschi, Elvira Bianco, Mario Salomone, Alfonso Mele, Piergiorgio Messa, Carmine Zoccali, Francesca Menniti Ippolito and the COVIDVaxDia Study Group
Vaccines 2025, 13(9), 935; https://doi.org/10.3390/vaccines13090935 - 1 Sep 2025
Viewed by 655
Abstract
Background: COVID-19 vaccination and subsequent booster doses became critical components of public health strategies to control the pandemic and reduce disease severity, especially in fragile individuals. Among these, subjects undergoing dialysis represent one of the highly vulnerable populations. Methods: We conducted a multicenter [...] Read more.
Background: COVID-19 vaccination and subsequent booster doses became critical components of public health strategies to control the pandemic and reduce disease severity, especially in fragile individuals. Among these, subjects undergoing dialysis represent one of the highly vulnerable populations. Methods: We conducted a multicenter case–control study among dialysis patients between March 2021 and May 2022 (study population n = 3264). We evaluated anti-S/RBD-IgG and anti-SARS-CoV-2 neutralizing antibodies before (T3) and after (T4) the third dose in individuals with a COVID-19 diagnosis after the third dose (cases) and in those who did not report infection (controls). Results: The study included 187 cases and 150 controls. Serological analysis showed a significant increase (p < 0.001) in anti-SARS-CoV-2 antibody levels after the third vaccine dose (from T3 to T4) in both groups. At T3, with the same number of days between the second dose and T3, the antibody levels detected were significantly lower in cases as compared to controls. At T4, we observed similar antibody titers in the two groups. Notably, the mean difference in time from the third dose to T4 was significantly greater in controls (73.0 days vs. 36.7, p < 0.001), suggesting a reduced antibody waning in controls. Accordingly, multivariate analysis showed that the risk of infection was considerably reduced by the pre-third-dose antibody levels. Conclusions: This study reinforces the critical role of the humoral response in preventing infections in the vulnerable population of dialysis patients. Regular monitoring of antibody levels and timely administration of booster doses are essential to optimize protection in this group. Full article
(This article belongs to the Section COVID-19 Vaccines and Vaccination)
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23 pages, 1289 KB  
Article
Development and Clinical Validation of a Skin Test for In Vivo Assessment of SARS-CoV-2 Specific T-Cell Immunity
by Tikhon V. Savin, Vladimir V. Kopat, Elena D. Danilenko, Alexey A. Churin, Anzhelika M. Milichkina, Edward S. Ramsay, Ilya V. Dukhovlinov, Andrey S. Simbirtsev and Areg A. Totolian
Viruses 2025, 17(9), 1186; https://doi.org/10.3390/v17091186 - 29 Aug 2025
Viewed by 1002
Abstract
A novel skin test for an in vivo assessment of SARS-CoV-2-specific T-cell immunity was developed using CoronaDermPS, a multiepitope recombinant polypeptide encompassing MHC II–binding CD4+ T-cell epitopes of the SARS-CoV-2 structural proteins (S, E, M) and full length nucleocapsid (N). In silico epitope [...] Read more.
A novel skin test for an in vivo assessment of SARS-CoV-2-specific T-cell immunity was developed using CoronaDermPS, a multiepitope recombinant polypeptide encompassing MHC II–binding CD4+ T-cell epitopes of the SARS-CoV-2 structural proteins (S, E, M) and full length nucleocapsid (N). In silico epitope prediction and modeling guided antigen design, which was expressed in Escherichia coli, was purified (>95% purity) and formulated for intradermal administration. Preclinical evaluation in guinea pigs, mice, and rhesus macaques demonstrated a robust delayed type hypersensitivity (DTH) response at optimal doses (10–75 µg), with no acute or chronic toxicity, mutagenicity, or adverse effects on reproductive organs. An integrated clinical analysis included 374 volunteers stratified by vaccination status (EpiVacCorona, Gam-COVID-Vac, CoviVac) prior to COVID-19 infection (Wuhan/Alpha, Delta, Omicron variants), and SARS-CoV-2–naïve controls. Safety assessments across phase I–II trials recorded 477 adverse events, of which >88% were mild and self-limiting; no severe or anaphylactic reactions occurred. DTH responses were measured at 24 h, 72 h, and 144 h post-injection by papule and hyperemia measurements. Overall, 282/374 participants (75.4%) exhibited a positive skin test. Receiver operating characteristic analysis yielded an overall AUC of 0.825 (95% CI: 0.726–0.924), sensitivity 79.5% (95% CI: 75.1–83.3%), and specificity 85.5% (95% CI: 81.8–88.7%), with comparable diagnostic accuracy across vaccine, and variant subgroups (AUC range 0.782–0.870). CoronaDerm-PS–based skin testing offers a simple, reproducible, and low-cost method for qualitative evaluation of T-cell–mediated immunity to SARS-CoV-2, independent of specialized laboratory equipment (Eurasian Patent No. 047119). Its high safety profile and consistent performance across diverse cohorts support its utility for mass screening and monitoring of cellular immune protection following infection or vaccination. Full article
(This article belongs to the Section Viral Immunology, Vaccines, and Antivirals)
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16 pages, 2673 KB  
Article
Immunogenic Responses Elicited by a Pool of Recombinant Lactiplantibacillus plantarum NC8 Strains Surface-Displaying Diverse African Swine Fever Antigens Administered via Different Immunization Routes in a Mouse Model
by Assad Moon, Hongxia Wu, Tao Wang, Lian-Feng Li, Yongfeng Li, Zhiqiang Xu, Jia Li, Yanjin Wang, Jingshan Huang, Tianqi Gao, Yuan Sun and Hua-Ji Qiu
Vaccines 2025, 13(9), 897; https://doi.org/10.3390/vaccines13090897 - 25 Aug 2025
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Abstract
Background: African swine fever (ASF) is a highly contagious and often deadly disease that poses a major threat to swine production worldwide. The lack of a commercially available vaccine underscores the critical need for innovative immunization strategies to combat ASF. Methods: Six ASFV [...] Read more.
Background: African swine fever (ASF) is a highly contagious and often deadly disease that poses a major threat to swine production worldwide. The lack of a commercially available vaccine underscores the critical need for innovative immunization strategies to combat ASF. Methods: Six ASFV antigenic proteins (K78R, A104R, E120R, E183L, D117L, and H171R) were fused with the Lactiplantibacillus plantarum WCFS1 surface anchor LP3065 (LPxTG motif) to generate recombinant Lactiplantibacillus plantarum NC8 (rNC8) strains. The surface expression was confirmed using immunofluorescence and Western blotting assays. Additionally, the dendritic cell-targeting peptides (DCpep) were co-expressed with each antigen protein. Mice were immunized at a dosage of 109 colony-forming units (CFU) per strain per mouse via intragastric (I.G.), intranasal (I.N.), and intravenous (I.V.) routes. The bacterial mixture was heat-inactivated by boiling for 15 min to destroy viable cells while preserving antigenic structures. I.V. administration caused no hypersensitivity, confirming the method’s safety and effectiveness. Results: Following I.G. administration, rNC8-E120R, rNC8-E183L, rNC8-K78R, and rNC8-A104R induced significant levels of secretory immunoglobulin A (sIgA) in fecal samples, whereas rNC8-H171R and rNC8-D117L failed to induce a comparable response. Meanwhile, rNC8-D117L, rNC8-K78R, and rNC8-A104R also elicited significant levels of sIgA in bronchoalveolar lavage fluid (BALF). Following I.N. immunization, rNC8-E120R, rNC8-K78R, and rNC8-A104R significantly increased sIgA levels in both fecal and BALF immunization. In contrast, I.V. immunization with heat-inactivated rNC8-K78R and rNC8-A104R induced robust serum IgG titers, whereas the remaining antigens elicited minimal or insignificant responses. Flow cytometry analysis revealed expanded CD3+CD4+ T cells in mice immunized via the I.N. and I.G. and CD3+CD4+ T cells only in those immunized via the I.N. route. Th1 responses were also significant in the sera of mice immunized via the I.G. and I.N. routes. Conclusions: The rNC8 multiple-antigen cocktail elicited strong systemic and mucosal immune responses, providing a solid foundation for the development of a probiotic-based vaccine against ASF. Full article
(This article belongs to the Special Issue Vaccines for Porcine Viruses)
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17 pages, 5140 KB  
Article
Comparative Analysis of Chitosan, Lipid Nanoparticles, and Alum Adjuvants in Recombinant SARS-CoV-2 Vaccine: An Evaluation of Their Immunogenicity and Serological Efficacy
by Majed Ghattas, Garima Dwivedi, Anik Chevrier, Trevor Scobey, Rakan El-Mayta, Melissa D. Mattocks, Dong Wang, Marc Lavertu and Mohamad-Gabriel Alameh
Vaccines 2025, 13(8), 788; https://doi.org/10.3390/vaccines13080788 - 24 Jul 2025
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Abstract
Background: Chitosan, a family of polysaccharides composed of glucosamine and N-acetyl glucosamine, is a promising adjuvant candidate for eliciting potent immune response. Methods: This study compared the adjuvant effects of chitosan to those of empty lipid nanoparticles (eLNPs) and aluminum hydroxide (alum) following [...] Read more.
Background: Chitosan, a family of polysaccharides composed of glucosamine and N-acetyl glucosamine, is a promising adjuvant candidate for eliciting potent immune response. Methods: This study compared the adjuvant effects of chitosan to those of empty lipid nanoparticles (eLNPs) and aluminum hydroxide (alum) following administration of recombinant SARS-CoV-2 spike immunogen in adult mice. Mice received the adjuvanted recombinant protein vaccine in a prime-boost regimen with four weeks interval. Subsequent analyses included serological assessment of antibody responses, evaluation of T cell activity, immune cell recruitment and cytokine profiles at injection site. Results: Compared to alum, chitosan induced a more balanced Th1/Th2 response, akin to that observed with eLNPs, demonstrating its ability to modulate both the humoral and cellular immune pathways. Chitosan induced a different proinflammatory cytokine (e.g., IL-1⍺, IL-2, IL-6, and IL-7) and chemokine (e.g., Eotaxin, IP-10, MIP-1a) profile compared to eLNPs and alum at the injection site and in the draining lymph nodes. Moreover, chitosan potentiated the recruitment of innate immune cells, with neutrophils accounting for about 40% of the infiltrating cells in the muscle, representing a ~10-fold increase compared to alum and a comparable level to eLNPs. Conclusions: These findings collectively indicate that chitosan has the potential to serve as an effective adjuvant, offering comparable, and potentially superior, properties to those of currently approved adjuvants. Full article
(This article belongs to the Special Issue Advances in Vaccine Adjuvants)
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