Search Results (2,230)

Background/Objectives: Understanding the durability of immunity induced by mRNA COVID-19 vaccines, especially in individuals with chronic health conditions, remains essential for guiding booster strategies. We conducted a longitudinal study to evaluate humoral and cellular immune responses up to 21 months after a primary two-dose BNT162b2 vaccination followed by a booster, either homologous (BNT162b2) or heterologous (mRNA-1273). Methods: Twenty-eight adults, mostly with chronic conditions, were assessed at approximately 9, 12 and 21 months post-primary vaccination. Serum anti-trimeric Spike IgG levels were quantified, and peripheral blood mononuclear cells were analyzed at 21 months for Spike-specific memory B-cell and T-cell responses by flow cytometry. Results: Participants were stratified by booster type, prior SARS-CoV-2 infection and health status. Anti-Spike IgG persisted in all participants but declined over time. The heterologous mRNA-1273 booster induced higher antibody titers at 9 months, while the homologous BNT162b2 booster led to more sustained antibody levels and higher frequencies of Spike-specific memory B cells at 21 months. Prior infection significantly enhanced antibody titers, particularly in homologous booster recipients. Surprisingly, individuals with chronic health conditions exhibited equal or higher antibody levels compared to healthy participants at all time points. At 21 months, robust Spike-specific class-switched memory B cells and polyfunctional CD4⁺ and CD8⁺ T-cell responses were detected. Conclusions: These findings demonstrate that BNT162b2 vaccination elicits durable, multi-layered immunity lasting nearly two years, even in individuals with chronic conditions, and support the use of both homologous and heterologous mRNA boosters to sustain protection in diverse populations. Full article

Egg yolk IgY antibody has significant application potential in aquaculture as a form of passive immunotherapy against various bacterial infections owing to its capacity for large-scale and cost-effective production. In this research, laying hens were immunized with live or inactivated Aeromonas hydrophila to produce IgY antibodies. Following this, experiments were carried out to assess the passive immune protection rates of the two types of IgY antibodies when used to immunize goldfish (Carassius auratus), which were then infected with A. hydrophila or Aeromonas veronii. ELISA experiments were conducted to demonstrate the interaction between the IgY antibodies and the bacteria. The kidneys of C. auratus were coated on a Luria–Bertani (LB) medium to evaluate bacterial content. The leukocyte phagocytosis was detected by a cell phagocytosis assay. The serum of C. auratus was used to assess the expression of antioxidant factors, and a qRT-PCR was conducted to evaluate the mRNA expression of inflammatory factors in visceral tissue. Furthermore, histopathology and immunofluorescence analysis were performed to evaluate the structural integrity, apoptosis, and DNA damage of visceral tissues. The results indicated that the live or inactivated A. hydrophila IgY antibodies exhibited passive immune protection rates against A. hydrophila and A. veronii and could recognize these two bacteria in vitro. Additionally, these two IgY improved the phagocytic ability of leukocytes, diminished renal bacterial concentration, and decreased the levels of antioxidant factors and mRNA expression of inflammatory factors. Meanwhile, the two IgY antibodies did not cause any pathology of the kidney, spleen, and intestine, and decreased the levels of DNA damage factor (γH2A.X) and cell apoptosis factor (p53) in renal tissue. Therefore, live and inactivated A. hydrophila IgY antibodies can resist bacterial infections, with live bacteria IgY providing greater protection than inactivated bacteria IgY. Further, A. hydrophila is an aquatic pathogen that causes minimal damage to laying hens, and the immunity of live A. hydrophila conforms to animal welfare. Altogether, live A. hydrophila IgY antibody can serve as a polyvalent passive immune vaccine candidate in aquaculture. Full article

Introduction: Vaccines are the most widely used public health measure to control the global COVID-19 pandemic. Most vaccines used in Europe and North America are mRNA-based. A mass vaccination campaign was carried out between 2021 and 2024. Some adverse events have been reported based on analogies with previous virus-attenuated vaccines. Objectives: Given the new mechanism inducing specific antibodies, we questioned the role of mRNA Spike vaccines and the significance of hyperproduction of anti-Spike antibodies in the emergence of early and late onset rheumatological manifestations observed after one or more injections. Material and Methods: A prospective observational study involving two cohorts was initiated. The first cohort was observed from 13 September 2021 to 30 September 2022, and the second cohort from 1 October 2022 to 30 September 2023. The study also focused on the interval between the last vaccine injection and the onset of rheumatic symptoms. None of the patients had a history of rheumatic or inflammatory diseases. We compared both cohorts and ankle arthritis case series to analyze the differences between early and late-onset adverse events. Results: In both cohorts and case series, the majority of patients were women. The most common symptoms included diffuse muscle pain, which mimics polymyalgia rheumatica, and ankle arthritis. Very high levels of anti-Spike antibodies (>2080 BAU/mL) were generally detected. The Pearson correlation coefficient between both cohorts and case series was very high, confirming the reproducibility of post-vaccine clinical and biological features. Conclusions: These rheumatological manifestations might be triggered by inappropriate individual immune responses to the vaccine’s Spike protein and/or the overproduction of Spike protein, which can mediate a pro-inflammatory reaction, explaining early and late-onset effects. Full article

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

Orthoflaviviruses belong to the flavivirus genus, which is part of the Flaviviridae family. Orthoflaviviruses include major clinically relevant arthropod-borne human viruses such as Dengue, Zika, yellow fever, West Nile and tick-borne encephalitis virus. These viruses pose an increasing threat to global health due to the expansion of arthropod habitats, urbanization, and climate change. While vaccines have been developed for certain orthoflaviviruses with varying levels of success, critical challenges remain in achieving broadly deployable vaccines that combine a robust safety profile with durable immunity against many current and emerging orthoflaviviruses. This review provides a snapshot of established and emerging vaccine platforms against orthoflaviviruses, with a particular emphasis on those leveraging the envelope glycoprotein E as the primary antigen. We examine the strengths and disadvantages of these different platforms in eliciting safe, durable, and robust orthoflavivirus immunity, and discuss how specific attributes such as multivalency, authentic epitope presentations, and logistical practicality can enhance their value in preventing orthoflavivirus infection and disease. Full article

Porcine Reproductive and Respiratory Syndrome (PRRS) causes significant economic losses in the swine industry. Circular RNAs (circRNAs), a class of stable non-coding RNAs, are increasingly recognized as regulators in immune responses and host–virus interactions. This study investigated the genome-wide circRNA responses in porcine alveolar macrophages (PAMs), key cell targets of PRRSV, following treatment with a modified live virus (MLV) vaccine or two interferon (IFN) subtypes (IFN-α1, IFN-ω5). Using RNA sequencing, we identified over 1000 differentially expressed circRNAs across treatment groups, revealing both conserved and distinct expression profiles. Gene Ontology and KEGG pathway analyses indicated that circRNA-associated genes are significantly enriched in immune-related processes and pathways, including cytokine signaling and antiviral defense. Notably, IFN-ω5 treatment induced a pronounced circRNA response, aligning with its potent antiviral activity. We further explored the regulatory potential of these circRNAs by predicting miRNA binding sites, revealing complex circRNA-miRNA interaction networks. Additionally, we assessed the coding potential of differentially expressed circRNAs by identifying open reading frames (ORFs), internal ribosome entry sites (IRESs), and N6-methyladenosine (m⁶A) modification sites, suggesting a subset may undergo non-canonical translation. These findings provide a comprehensive landscape of circRNA expression in PAMs under different antiviral conditions, highlighting their potential roles as immune regulators and novel players in interferon-mediated antiviral responses, particularly downstream of IFN-ω5. This work contributes to understanding the non-coding RNA landscape in the PRRSV-swine model and suggests circRNAs as potential targets for future antiviral strategies. Full article

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

Non-viral myocarditis is rare but relatively more frequent in patients with systemic autoimmune diseases (such as systemic lupus erythematosus, SLE, and allied conditions) than in the general population. In rare cases, mRNA-based vaccines can also trigger non-viral myocarditis. Limited data are available about the cardiac safety of mRNA vaccines in this subset of patients. Here, we report data from a third-level hospital on long-term safety, leveraging on a previously described cohort of 13 consecutive patients with SLE, Undifferentiated (UCTD) and Mixed Connective Tissue disease (MCTD), and a history of myocarditis, who had received anti-COVID-19 vaccination between April 2021 and January 2022. Demographics and clinical data (including validated clinometric for SLE) were collected at baseline, at the first available visit following the primary vaccination cycle, after an additional 12 months, and at the last available follow-up after at least 36 months. Twelve patients, seven females, ten with SLE, one MCTD, and one UCTD, had a median follow-up of 41 (35–45) months. One patient was lost at follow-up. No disease flare or sign of myocarditis recurrence were observed. At last visit, all patients were in a low disease activity state (LLDAS), and all but one were in remission, according to the Definition of Remission in SLE (DORIS) criteria. No significant variations in disease activity or damage accrual nor in markers of inflammation and myocardial injury were observed. Our data suggest that mRNA-based anti-COVID-19 vaccines in patients with previous autoimmune myocarditis in the context of SLE and allied conditions have a good long-term safety profile. Full article

Introduction (Objectives): This study aimed to evaluate the serological response to a fourth dose of mRNA COVID-19 vaccine in patients with conditions that confer a high risk of severe disease, particularly those with high-level immunosuppression. Methods: An observational study was conducted at the Ramón y Cajal University Hospital between February and August 2022. Adults (≥18 years) with high-risk conditions who had received four doses of either BNT162b2 or mRNA-1273 were included. Anti-spike IgG levels were measured ≥14 days post-vaccination. An adequate response was defined as an antibody concentration ≥260 BAU/mL. Results: A total of 943 patients were analyzed; 846 (89.7%) achieved an adequate response. In the bivariate analysis, patients aged 60–74 years had a higher risk of inadequate response compared to those aged 18–39 years (OR 1.824 vs. OR 0.257). Female sex was associated with a higher risk of inadequate response (OR 1.522; 95% CI: 0.974–2.371). In multivariable logistic regression, patients with high immunosuppression had a higher, though not statistically significant, risk of inadequate response compared with those without. Discussion: Our findings are consistent with international evidence suggesting that age and certain clinical factors reduce vaccine immunogenicity. The observed paradoxical effect of sex could reflect the higher prevalence of aggressive immunosuppressive therapies among women in the study cohort. Conclusions: Most immunosuppressed patients achieved seroconversion after the fourth dose. These results underscore the need for tailored vaccination strategies and additional measures in highly immunosuppressed subgroups. Full article

Recent advances in biotechnology have fundamentally reshaped the landscape of vaccine development, offering innovative strategies to improve immunogenicity, safety and accessibility. This review explores the cutting-edge platforms—including mRNA, DNA, virus-like particles, viral and bacterial vectors, and bacteriophage-based vaccines—that are redefining how vaccine antigens are delivered to the immune system. We also discuss alternative delivery methods, such as transcutaneous and mucosal immunization, which have the potential to improve vaccine acceptance and distribution, as well as next-generation adjuvants targeting innate immune receptors aiming to further enhance vaccine efficacy, especially in vulnerable populations. By synthesizing these innovations, this review highlights how biotechnology is enabling the design of safer, more efficient, and more adaptable vaccines to address both existing and emerging infectious diseases. Full article

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

Immunotherapy, consisting mainly of immune checkpoint inhibitors, has been successfully employed in the treatment of early and advanced-stage melanoma for more than ten years. Personalized mRNA vaccines represent the next evolutionary step, offering patients a treatment unique to them and their tumor, whilst putting recent, significant technological and scientific advances into practice. Clinical and preclinical data about mRNA vaccines are now emerging, further encouraging research and spreading enthusiasm among patients and physicians. Nonetheless, a lot remains to be discovered about mRNA vaccines’ mechanisms of action, their actual effect on the immune cells of the patient, and successful mRNA delivery to the host. Full article

Non-Saccharomyces yeasts are emerging as promising new probiotics with a beneficial effect equal to or greater than the reference probiotic yeast, Saccharomyces boulardii. Candida intermedia, a non-albicans species not considered a common human pathogen, previously demonstrated probiotic potential. In this work, our objective was to evaluate the immunomodulatory effects of C. intermedia ORQ001 in mice vaccinated with inactivated SARS-CoV-2, seeking further evidence of its probiotic activity. Murine macrophages were stimulated with C. intermedia, followed by mRNA transcription analysis via qPCR. Mice were supplemented with C. intermedia prior to SARS-CoV-2 vaccination. Antibody production was assessed by ELISA, and fecal microbiomes were analyzed using next-generation sequencing. C. intermedia significantly increased Il4 and Il13 expression while decreasing Stat3 in macrophages. Splenocytes from supplemented mice exhibited elevated transcription levels of Tnf, Ifng, Il4, Bcl6, and Stat3 after exposure to stimulatory molecules. These mice showed increased levels of anti-SARS-CoV-2 IgG and sIgA isotypes, along with higher abundances of Bacteroides spp. and Clostridium spp. in their gut microbiome. In conclusion, C. intermedia supplementation modulated the expression of key immune-related genes and enhanced humoral responses in mice. Furthermore, its influence on gastrointestinal microbiota suggests a synergistic effect on vaccine immunogenicity. These findings support the potential of C. intermedia as a novel probiotic candidate with immunomodulatory properties applicable to vaccine adjuvanticity. Full article