Search Results (161)

Background and Objective: Evaluating vaccine effectiveness (VE) is essential to implementing prevention strategies, and our objective was to estimate the VE of SARS-CoV-2 messenger RNA (mRNA) vaccines in preventing SARS-CoV-2 infection. Materials and Methods: We carried out a population-based, prospective cohort study on the Borriana COVID-19 cohort (Valencia Community, Spain) during the 2021–2023 period, considering all SARS-CoV-2 cases that occurred after the SARS-CoV-2 vaccine campaign started in January 2021 (first approach), as well as only symptomatic cases (second approach). Multivariable robust Poisson regression models were employed. Results: In this cohort with 301 participants, 285 were vaccinated, among whom 228 received only SARS-CoV-2 mRNA vaccines, and 57 received mRNA vaccines and other vaccines. In the first approach, there were 226 cases and 75 non-cases. The adjusted VE for three doses of vaccine was 37% (95% confidence interval [CI]: 22–49%) to prevent infection. In the second approach, with 153 symptomatic cases after excluding 73 asymptomatic cases, the adjusted VE for three doses of vaccine was 50% (95% CI 33–63%) to prevent symptomatic infection. Three doses of vaccine exhibited modest but significant protection against infection and symptomatic infection. Conclusions: This study recommends surveilling SARS-CoV-2 infections and variants, vaccinating at-risk populations, and developing new vaccines. Full article

Background/Objectives: In previous studies, we demonstrated that the HIV-1 Env-Gag VLP mRNA vaccine elicited superior cellular immune responses. In this study, we further evaluated the immunogenicity of the Env-Gag VLP mRNA and adenovirus vector vaccines when administered individually or in combination in mice. Methods: BALB/c mice were divided into four groups and immunized twice at a 3-week interval. The three groups received either the Env-Gag VLP mRNA vaccine, the adenovirus vector vaccines expressing env and gag genes, or PBS as a control. The fourth group received a prime-boost regimen, primed with the Env-Gag mRNA vaccine and boosted with the adenovirus vector vaccines. The HIV-1 specific cellular and humoral immune responses were measured 1, 2, 4 and 8 weeks after the last immunization. Results/Conclusions: The results showed that the mRNA vaccines prime-adenovirus vector vaccines boost elicited higher cellular immune responses than those induced by homologous regimens at multiple time points, especially 8 weeks after the last immunization. Although the level of gp120 binding antibody in the combined immunization group is significantly lower than that of in the VLP mRNA vaccine group, a more balanced Th1/Th2 responses were induced in the combined immunization group, and significantly higher and longer-lasting neutralizing antibody levels were detected in this group making it a very promising HIV vaccine strategy. Full article

Background/Objectives: The coronavirus disease 2019 (COVID-19) pandemic imposed an unprecedented global health and economic burden, prompting rapid implementation of diverse public health interventions. This review aimed to synthesize global evidence on the cost-effectiveness of key COVID-19 control strategies, including vaccination, testing, and social distancing and to identify methodological, contextual, and equity-related determinants of their economic value. Methods: A narrative literature review was conducted using peer-reviewed studies published between January 2020 and September 2025 and indexed in PubMed, Scopus, and Web of Science. Eligible studies included economic evaluations and modeling analyses addressing COVID-19 interventions in healthcare, community, or educational settings. Data on costs, outcomes, and methodological features were extracted and synthesized descriptively. Results: Across 74 included studies, vaccination—particularly with messenger RNA (mRNA) platforms—emerged as the most cost-effective intervention across all settings, often cost-saving among high-risk populations. Combined or layered strategies integrating vaccination, testing, and selective social distancing consistently outperformed single interventions in both health and economic outcomes. Early and targeted implementation yielded the highest cost-effectiveness by preventing exponential transmission and healthcare overload. However, heterogeneity in modeling assumptions, analytic perspectives, and outcome measures limited comparability. Few studies applied extended or distributional cost-effectiveness frameworks to address equity, while indirect and long-term effects such as productivity losses and “long COVID” were frequently omitted. Conclusions: COVID-19 interventions are most efficient when early, targeted, and adaptive to local epidemiologic conditions. Integrating equity, methodological consistency, and broader societal impacts into future evaluations will strengthen evidence-based, economically sustainable pandemic preparedness and response strategies. Full article

Messenger RNA therapy represents a transformative therapeutic in vaccine development, tumor immunotherapy, and genetic disease intervention. Polyethylene glycol (PEG) lipid, a key component of ionizable lipid nanoparticles (iLNPs) for mRNA delivery, and the PEG antibodies induced by PEG are associated with hypersensitivity and accelerated blood clearance. To address the above PEG-associated challenges, we systematically investigated polysorbate 20 (PS20) as an alternative for constructing PEG-free iLNPs. The formulation of PS20-incorporated iLNPs (PS20-iLNPs) for carrying mRNA was systematically investigated by analyzing the particle size, pKa, endosomal escape efficiency, and cellular internalization efficiency of iLNPs with different molar ratio PS20 content (0.5–5.0%). iLNPs with a relative molar ratio of 2.5% were identified as the optimal mRNA delivery carrier. This carrier exhibited excellent resistance to serum protein adsorption capacity, with serum stability 1.3-fold higher than PEG-iLNPs. At high lipid concentrations (2.7 mg/mL), the cell viability of PS20-iLNPs was maintained at 91.1%, which was 1.07-fold higher than PEG-iLNPs. Under serum interference, PS20-iLNPs achieved a transfection efficiency of 46.5%, marking a 10.6% improvement over PEG-iLNPs under identical conditions. Notably, PS20-iLNPs exhibited 24 times higher spleen accumulation than PEG-iLNPs. These findings highlight PS20 as a viable PEG substitute for developing PEG-free spleen-accumulated mRNA delivery platforms with enhanced therapeutic potential. Full article

Dengue virus remains a major global health threat due to the lack of a safe and broadly effective vaccine. Traditional antibody-based vaccines often show limited protection and can exacerbate disease severity in individuals without prior exposure. A new generation of T-cell epitope-based vaccines offers a promising and safer approach by activating the cellular arm of the immune system to complement antibody responses. Instead of targeting only surface structural proteins, these vaccines focus on highly conserved peptide regions within non-structural proteins, particularly NS3 and NS5, that are shared across all four dengue virus serotypes. Peptides such as DTTPFGQQR, KPGTSGSPI, and MYFHRRDLRL have been identified as potent immunogenic targets capable of inducing strong cytotoxic and helper T-cell responses, promoting viral clearance and long-term immune memory. Advanced immunoinformatic enables precise prediction and selection of epitopes with high binding affinity to human leukocyte antigens and broad cross-serotype conservation. These peptides can be integrated into next-generation vaccine delivery systems, including messenger RNA and nanoparticle platforms, which enhance antigen presentation, improve molecular stability, and reduce the risk of antibody-dependent disease enhancement. Together, this integrative design represents a rational path toward a safer, cross-protective, and durable dengue vaccine that closely mimics the balanced cellular and humoral immunity observed after natural infection, offering renewed hope for effective global dengue prevention. 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

Background: Messenger RNA-lipid nanoparticle (mRNA-LNP) is a cutting-edge nucleic acid intracellular delivery technology. Although the clinical use of the mRNA vaccine is being actively developed, the use of mRNA-LNP technology in common diseases such as allergies is still being investigated. The purpose of this study is to test if immune response can be suppressed when an antigen is expressed in mice liver tissue with mRNA-LNP technology. Methods: We first designed mRNA which the ovalbumin (OVA) antigen expresses on the surface of the cells, and synthesized mRNA were encapsulated into LNP. This OVA-mRNA-LNP was evaluated with an OVA-sensitized mouse model. Splenocytes from OVA-sensitized mice were cultured with ex vivo OVA stimulation for Th2 cytokine production and Treg population analysis. Furthermore, OVA-mRNA-LNP was evaluated by both prophylactic and therapeutic administration in an OVA-induced mice airway inflammation model. Results: Th2 cytokines such as IL-4 and IL-5 were suppressed and the Treg population was increased in ex vivo OVA-stimulated splenocytes isolated from the OVA-mRNA-LNP administered group. Moreover, suppression of Th2 cytokines in Bronchoalveolar Lavage Fluid (BALF) from both the prophylactic and therapeutic OVA-mRNA-LNP administered cohort was observed (40–80% reduction in Th2 cytokines). Conclusions: The data suggests that mRNA-LNP technology, which is a safe, non-viral gene delivery system, can be an effective approach to suppress allergen-induced inflammation by expressing antigen in the liver tissue. Full article

Immunotherapy is now an established therapy for nearly a third of patients with cancer. Most therapies, typically using cytokines or checkpoint blockade therapy, rely on global activation of immune effector cells. The ability of vaccines to activate specific populations of cells has led to a renewed interest in their ability to treat cancers, either alone or with other immune therapies or other conventional therapies. The COVID-19 pandemic sparked a new interest in nucleic acid vaccines with the development of new technologies and the short manufacturing time for vaccine implementation. Nucleic acid-based cancer vaccines have been studied for decades, but have shown modest anti-tumor efficacy as monotherapies, as many of these vaccines encode for shared tumor-associated antigens (TAAs) and must overcome immune tolerance. New developments, technologies, routes of delivery, and combination therapies have paved the way for new approaches and clinical trials involving nucleic acid vaccines for the treatment of cancer. Here we review mRNA and pDNA vaccines for the treatment of cancer, including similarities and differences in their mechanisms of action, an overview of these treatment modalities in preclinical and clinical studies, methods to improve these vaccine strategies, and exciting new combination approaches in development. Full article

Funded during the emergency phase of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, messenger RNA (mRNA) vaccines are single-stranded, 5′-capped mRNAs produced using a cell-free in vitro transcription from the corresponding plasmid DNA (pDNA) templates, encoding the viral spike (S) protein of SARS-CoV-2 [...] Full article

Messenger RNA (mRNA) vaccine technology has revolutionized the field of immunization, offering a non-infectious, non-genome-integrating platform that addresses many limitations of traditional vaccine modalities. Recent advancements in chemical modifications, delivery systems, and manufacturing processes have enhanced the stability, efficacy, and safety of RNA-based therapeutics, expanding their application beyond infectious diseases to include genetic disorders, cancer, and rare diseases. Central to the success of RNA vaccines is their ability to orchestrate a finely tuned immune response, leveraging both innate and adaptive immunity to achieve robust and durable protection. This review synthesizes current knowledge on the immunological mechanisms underpinning RNA vaccine efficacy, with a focus on the roles of pattern recognition receptors (PRRs) such as Toll-like receptors (TLRs) and RIG-I-like receptors (RLRs) in sensing exogenous RNA, the impact of RNA modifications and manufacturing impurities on innate immune activation, and the subsequent cytokine and chemokine milieu that shapes adaptive responses. We also discuss the dual role of lipid nanoparticle (LNP) delivery systems as both carriers and adjuvants, highlighting their contribution to the vaccine’s immunogenicity and reactogenicity profile. Understanding these complex immune interactions is critical for optimizing RNA vaccine design, minimizing adverse effects, and expanding their therapeutic potential. This review aims to provide a comprehensive overview of the immune symphony orchestrated by RNA vaccines and to identify key areas for future research to further refine and expand the utility of this transformative technology. Full article

Background: Evidence on the humoral and cellular immune responses to SARS-CoV-2 following COVID-19 vaccination in older adults is warranted. Aims: To synthesize and analyze the current evidence on humoral and cellular immune responses to both standard and booster COVID-19 vaccination in individuals aged 60 years and older. Methods: Clinical trials and observational studies were included. Reviews, case series, letters to the editor, and similar publications were excluded. A selective literature search was conducted in the following databases: PubMed, Scopus, EMBASE, and Web of Science. The risk of bias and methodological quality of the included studies were assessed using the Newcastle–Ottawa Scale (NOS) and the Risk of Bias 2.0 (RoB 2) tool. Statistical analysis was conducted using Stata version 18 and Review Manager version 5.4.1. Results: Thirteen studies were included: eleven observational studies and two randomized clinical trials, evaluating humoral and cellular immune responses in 782 older adults. Messenger RNA vaccines were the most administered, particularly Pfizer-BioNTech (76.9%) and Moderna mRNA-1273 (23%). In most cases, immune responses were assessed after the second dose and booster doses. Most studies (61.5%) reported increased IgG titers specific to the SARS-CoV-2 Spike protein, while 23.1% reported a decrease. Regarding cellular immunity, 46.2% of the studies reported low interferon-gamma (IFN-γ) levels post-vaccination, whereas 38.5% showed increases. These findings highlight the need for tailored vaccination strategies to address emerging variants, particularly in vulnerable populations such as older adults. Conclusions: In older adults receiving COVID-19 vaccination, humoral immunity tends to increase, whereas cellular responses are frequently diminished, reflecting age-related immunosenescence that may limit the durability and breadth of protection following vaccination in older adults. Full article

Introduction: Following up on treated high-grade cervical intraepithelial neoplasia (HSIL/CIN) lesions poses a challenge. Cervical cytology often has a high false-negative rate, while high-risk human papillomavirus (HR-HPV) DNA testing, though sensitive, lacks specificity. The detection of messenger RNA of the HR-HPV E6 and E7 oncoproteins (E6/E7 mRNA) is proposed as an indicator of viral integration, which is crucial for identifying severe lesions. Additionally, HPV vaccination could reduce recurrence rates in patients treated for high-grade cervical intraepithelial neoplasia. Objective: Our study aimed to assess the clinical utility of E6/E7 mRNA determination in the follow-up of HPV-immunized patients who were treated for HSIL/CIN. Methods: We conducted a retrospective observational study including 407 patients treated for HSIL/CIN. The recurrence rate and the validity parameters of E6/E7 mRNA testing were analyzed. Results: The recurrence rate for high-grade lesions was 1.7%. This low percentage might be related to the vaccination of patients who were not immunized before treatment. The sensitivity of the E6/E7 mRNA test was 88% at the first clinical visit, reaching 100% in the second and third reviews. Specificity was 91% at the first visit, 92% at the second, and 85% at the third. Regarding predictive values, the positive predictive value was 18% at the first visit, 10% at the second, and 14% at the third, while the negative predictive value was 100% across all follow-up visits. Conclusions: The E6/E7 mRNA test appears to be an effective tool for ruling out recurrence after treatment for HSIL/CIN lesions in HPV-immunized patients. Full article

Background. The STING protein is activated by the second messenger cGAMP to promote the innate immune response against infections. Beyond this role, a chronically overactive STING signaling has been described in several disorders. Patients with severe COVID-19 exhibit a hyper-inflammatory response (the cytokine storm) that is in part mediated by the cGAS-STING pathway. Several STING inhibitors may protect from severe COVID-19 by down-regulating several inflammatory cytokines. This pathway has been implicated in the establishment of an optimal antiviral vaccine response. STING agonists as adjuvants improved the IgG titers against the SARS-CoV-2 Spike protein vaccines. Methods. We investigated the association between two common functional STING1/TMEM173 polymorphisms (rs78233829 C>G/p.Gly230Ala and rs1131769C>T/p.His232Arg) and severe COVID-19 requiring hospitalization. A total of 801 non-vaccinated and 105 fully vaccinated (mRNA vaccine) patients, as well as 300 population controls, were genotyped. Frequencies between the groups were statistically compared. Results. There were no differences for the STING1 variant frequencies between non-vaccinated patients and controls. Vaccinated patients showed a significantly higher frequency of rs78233829 C (230Gly) compared to non-vaccinated patients (CC vs. CG + GG; p = 0.003; OR = 2.13; 1.29–3.50). The two STING1 variants were in strong linkage disequilibrium, with the rs78233829 C haplotypes being significantly more common in the vaccinated (p = 0.02; OR = 1.66; 95%CI = 1.01–2.55). We also studied the LTZFL1 rs67959919 G/A polymorphism that was significantly associated with severe COVID-19 (p < 0.001; OR = 1.83; 95%CI = 1.28–2.63). However, there were no differences between the non-vaccinated and vaccinated patients for this polymorphism. Conclusions. We report a significant association between common functional STING1 polymorphisms and the risk of developing severe COVID-19 among fully vaccinated patients. Full article

Background/Objectives: SARS-CoV-2 vaccine candidates comprising the receptor binding domain (RBD) of the spike protein have been shown to confer protection against infection. Previous research evaluating vaccine candidates with SARS-CoV-2 RBD fused to ferritin (RBD-ferritin) and other scaffolds suggested that multimeric assemblies of RBD can enhance antigen presentation to improve the potency and breadth of immune responses. Though RBDs directly fused to a self-assembling scaffold can be delivered as messenger RNA (mRNA) formulated with lipid nanoparticles (LNPs), reports of SARS-CoV-2 vaccine candidates that combine these approaches remain scarce. Methods: Here, we designed RBD fused to AP205 or TIP60 self-assembling nanoparticles following a search of available structures focused on several scaffold properties. RBD-AP205 and RBD-TIP60 were tested for antigenicity following transfection and for immunogenicity and neutralization potency when delivered as mRNA in mice, with RBD-ferritin as a direct comparator. Results: All scaffolded RBD constructs were readily secreted to transfection supernatant and showed antigenicity in ELISA, though clear heterogeneity in assembly was observed. RBD-AP205 and RBD-TIP60 also exhibited robust antibody binding and neutralization titers in mice that were comparable to those elicited by RBD-ferritin or a full-length membrane-bound spike. Conclusions: These data suggest that AP205 and TIP60 can present RBD as effectively as ferritin and induce similar immune responses. By describing additional scaffolds for multimeric display that accommodate mRNA delivery platforms, this work can provide new tools for future vaccine design efforts. Full article

Background: Acinetobacter baumannii (A. baumannii) has emerged as a critical human pathogen, causing high mortality rates among hospitalized patients and frequently triggering nosocomial outbreaks. The increasing prevalence of multidrug-resistant (MDR) A. baumannii poses a pressing threat to public health. To date, no commercially available vaccine against A. baumannii has been developed for clinical use. messenger RNA (mRNA)–lipid nanoparticle (LNP) vaccines have emerged as a promising vaccination strategy. Methods: In this work, we developed two mRNA vaccines targeting SmpA-PLD and the fusion protein of outer membrane proteins OmpK and Omp22. The mRNA was encapsulated in LNP and administered to BALB/c mice. We evaluated humoral and cellular immune responses, bacterial burden, inflammation, and protective efficacy against A. baumannii infection in a sepsis model. Results: These mRNA vaccines triggered robust humoral and cellular immune responses in BALB/c mice, reduced bacterial burden and inflammation in sepsis models, and provided significant protection against A. baumannii infection. Notably, the OmpK-Omp22 vaccine exhibited superior protective efficacy, reducing bacterial loads in various organs and improving survival rates in the sepsis model compared to the SmpA-PLD vaccine. Conclusions: Our findings demonstrate mRNA-LNP vaccine technology as a versatile and promising platform for the development of innovative therapeutics against A. baumannii, with the potential to mitigate acute disease and promote bacterial decolonization. These findings pave the way for the development of urgently needed and effective antibacterial vaccines. Full article