Search Results (1,245)

Since late 2023, an increase in Bordetella pertussis infections has been noticed in Europe, particularly among children. Our data showed the upward trend of B. pertussis cases in the Lazio region, even among adults with severe influenza-like illnesses, highlighting the necessity for maintaining high vaccination rates across both children and adults. These findings underscore the urgent need for clinicians to maintain a high index of suspicion for B. pertussis in patients with respiratory symptoms, prioritize nasopharyngeal swabs for accurate diagnosis, assess for co-infections, verify booster vaccination status in adults, and support timely reporting to public health authorities. Full article

Background/Objectives: This retrospective multicenter study, conducted within the ORCHESTRA Project, investigated SARS-CoV-2 reinfections among 5777 healthcare workers (HCWs) from four University Hospitals (Modena, Verona, Padova and Trieste) in northern Italy, aiming to assess the risk of reinfection and its determinants, comparing the clinical characteristics of reinfections with those of first infections, and examining the impact of preventive measures and vaccination strategies. Methods: HCWs completed an online questionnaire between June and August 2022. The survey collected demographic, occupational, and clinical data, including information on first infections and reinfections. Statistical analyses were performed using SPSS 28.0, through bivariate and multivariate approaches. Results: Response rates were 41.8% for Modena, 39.5% for Verona, 17.9% for Padova, and 17.4% for Trieste. Among the respondents, 4.8% (n = 276) experienced 2 infections and 0.5% (n = 27) reported 3 infections, out of a total of 330 reinfection cases. Additionally, 43.0% (n = 2787) reported only one infection, while 51.5% were never infected. Reinfection rates increased across five study phases (based on the epidemiological context), likely due to the emergence of new SARS-CoV-2 variants. A booster vaccine dose significantly reduced reinfection risk. Higher reinfection risk was found among HCWs aged ≤30 years, those with chronic respiratory diseases, and those working in COVID-19 wards, particularly nurses and allied health professionals. Reinfections were associated with a lower frequency of symptoms both during the period of swab positivity and after a negative swab, as well as with a shorter duration of swab positivity. No significant differences in symptom duration were found between first infections and reinfections. Conclusions: Despite its limitations, the online questionnaire proved a useful tool. Natural infection and vaccination reduced both reinfection risk and symptom severity. Prior infections should be considered in planning vaccination schedules and prioritizing HCWs. Full article

Background: Despite decades of high childhood vaccination coverage, pertussis has re-emerged in the Autonomous Province of Vojvodina (AP Vojvodina), Serbia. We aimed to describe the temporal, seasonal, and age-specific patterns of pertussis in AP Vojvodina and to analyze trends by vaccination status in order to highlight changes in epidemiology and potential gaps in vaccine-induced protection. Methods: We retrospectively analyzed 2796 pertussis cases reported between January 1997 and December 2024, examining temporal, seasonal, and age-specific trends, stratifying by vaccination status across four consecutive periods (1997–2003, 2004–2010, 2011–2017, and 2018–2024). Results: Throughout the 28-year period, after low and sporadic cases in the pre-2012 period, a dramatic rise was observed in 2014, 2017, and 2018, culminating in the highest annual number of reported cases in 2024 (1011 cases). Throughout this period, primary vaccination coverage with the DTwP/DTaP three-dose series ranged between 91% and 98%, while first booster coverage gradually declined from 98% in the early 2000s to 83% in 2024. Regarding seasonality, a sharp increase in cases began in 2012, peaking in November 2023 (>350 cases) and early 2024 (312 in January, 268 in February), with a seasonal shift from summer peaks in the 2011–2017 period to higher incidence rates during colder months more recently. Adolescents aged 10–14 years had the highest cumulative incidence (1149.4/100,000), followed by infants under 12 months (978.5/100,000), despite the latter representing fewer absolute cases. The proportion of pertussis in fully vaccinated individuals rose from 6.3% (1997–2003) to 49.7% (2018–2024). Conclusions: These findings suggest that booster immunization in adolescence and routine maternal vaccination during pregnancy could reduce transmission, particularly to infants. Enhanced surveillance and updated immunization policies are critical to mitigating future pertussis outbreaks. Full article

Background/Objectives: mRNA vaccines introduced during the COVID-19 pandemic were a significant step forward in the rapid development and deployment of vaccines in a global pandemic context. These vaccines showed good protective efficacy, but—due to limited breadth of the immune response—they required frequent boosters with manufactured spike sequences that often lagged behind the circulating strains. In order to enhance the breadth, durability, and magnitude of immune responses, we studied the effect of combining priming with an RNA vaccine technology with boosting with protein/adjuvant using a TLR4-agonist based adjuvant. Methods: Specifically, four proprietary adjuvants (EmT4^TM, LiT4Q^TM, MiT4^TM, and AlT4^TM) were investigated in combination with multiple modes of SARS-CoV-2 vaccination (protein, peptide, RNA) for their effectiveness in boosting antibody responses to SARS-CoV-2 spike protein in murine models. Results: Results showed significant improvement in immune response strength and breadth—especially against more distant SARS-CoV-2 variants such as Omicron—when adjuvants were used in combination with boosters following an RNA vaccine prime. Conclusions: The use of novel TLR4 adjuvants in combination with protein or RNA vaccinations presents a promising strategy for improving the efficacy of vaccines in the event of future pandemics, by leveraging rapid response using an RNA vaccine prime and following up with protein/adjuvant-based vaccines to enhance the breadth of immunity. Full article

The COVID-19 pandemic accelerated the rapid development and distribution of various vaccine platforms, resulting in a significant reduction in disease severity, hospitalizations, and mortality. However, persistent challenges remain concerning the durability and breadth of vaccine-induced protection, especially in the face of emerging SARS-CoV-2 variants. This review aimed to evaluate the factors influencing the immunogenicity and effectiveness of COVID-19 vaccines to inform future vaccine advancement strategies. A narrative review with systematic approach was conducted following PRISMA guidelines for narrative review. Literature was sourced from databases including PubMed, Embase, and Web of Science for studies published between December 2019 and May 2025. Encompassed studies assessed vaccine efficacy, immunogenicity, and safety across various populations and vaccine platforms. Data were collected qualitatively, with quantitative data from reviews highlighted where available. We have uncovered a decline in vaccine efficacy over time and weakened protection against novel variants such as Delta and Omicron. Booster doses, specifically heterologous regimens, improved immunogenicity and increased protection. Vaccine-induced neutralizing antibody titers have been found to correlate with clinical protection, although the long-term correlates of immunity remain poorly defined. The induction of IgG4 antibodies after repeated mRNA vaccinations raised concerns about potential modulation of the immune response. COVID-19 vaccines have contributed significantly to pandemic control; however, their efficacy is limited by the evolution of the virus and declining immunity. Forthcoming vaccine strategies should focus on broad-spectrum, variant-adapted formulations and defining robust comparisons of protection. Recognizing the immunological basis of vaccine response, including the role of specific antibody subclasses, is fundamental for optimizing long-term protection. Full article

Background: Kidney transplant recipients (KTRs) exhibit a significantly diminished immune response to Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) vaccines compared with the general population, primarily due to ongoing immunosuppressive therapy. This study evaluated the immunogenicity of a third SARS-CoV-2 mRNA vaccine dose in KTRs and assessed the association between antibody response and protection against SARS-CoV-2 breakthrough infection. Additionally, the clinical and immunological correlates of post-vaccination SARS-CoV-2 infection were examined. Methods: A prospective cohort of 135 KTRs received a third vaccine dose approximately six months following the second dose. Plasma samples were collected at baseline (pre-vaccination), six months after the second dose, and six weeks following the third dose. Humoral responses were assessed using SARS-CoV-2-specific Immunoglobulin G (IgG) titers and virus neutralization assays against wild-type (WT) and viral strains, including multiple Omicron sub-lineages. Results: After the third vaccine dose, 74% of the KTRs had detectable SARS-CoV-2-specific IgG antibodies, compared with 48% following the second dose. The mean IgG titers increased approximately ten-fold post-booster. Despite this increase, neutralizing activity against the Omicron variants remained significantly lower than that against the WT strain. KTRs who subsequently experienced a SARS-CoV-2 breakthrough infection demonstrated reduced neutralizing antibody activity across all variants tested. Additionally, individuals receiving triple immunosuppressive therapy had a significantly higher risk of SARS-CoV-2 breakthrough infection compared with those on dual or monotherapy. A multivariate machine learning analysis identified age and neutralizing activity against WT, Delta, and Omicron BA.2 as the most robust correlates of SARS-CoV-2 breakthrough infection. Conclusions: A third SARS-CoV-2 mRNA vaccine dose significantly improves SARS-CoV-2-specific IgG levels in KTRs; however, the neutralizing response against Omicron variants remains suboptimal. Diminished neutralizing capacity and intensified immunosuppression are key determinants of SARS-CoV-2 breakthrough infection in this immunocompromised population. Full article

Narrative review synthesizes the most current literature on the SARS-CoV-2 XEC variant, focusing on its genomic evolution, immune evasion characteristics, epidemiological dynamics, and public health implications. To achieve this, we conducted a structured search of the literature of peer-reviewed articles, preprints, and official surveillance data from 2023 to early 2025, prioritizing virological, clinical, and immunological reports related to XEC and its parent lineages. Defined by the distinctive spike protein mutations, T22N and Q493E, XEC exhibits modest reductions in neutralization in vitro, although current evidence suggests that mRNA booster vaccines, including those targeting JN.1 and KP.2, retain cross-protective efficacy against symptomatic and severe disease. The XEC strain of SARS-CoV-2 has drawn particular attention due to its increasing prevalence in multiple regions and its potential to displace other Omicron subvariants, although direct evidence of enhanced replicative fitness is currently lacking. Preliminary analyses also indicated that glycosylation changes at the N-terminal domain enhance infectivity and immunological evasion, which is expected to underpin the increasing prevalence of XEC. The XEC variant, while still emerging, is marked by a unique recombination pattern and a set of spike protein mutations (T22N and Q493E) that collectively demonstrate increased immune evasion potential and epidemiological expansion across Europe and North America. Current evidence does not conclusively associate XEC with greater disease severity, although additional research is required to determine its clinical relevance. Key knowledge gaps include the precise role of recombination events in XEC evolution and the duration of cross-protective T-cell responses. New research priorities include genomic surveillance in undersampled regions, updated vaccine formulations against novel spike epitopes, and long-term longitudinal studies to monitor post-acute sequelae. These efforts can be augmented by computational modeling and the One Health approach, which combines human and veterinary sciences. Recent computational findings (GISAID, 2024) point to the potential of XEC for further mutations in under-surveilled reservoirs, enhancing containment challenges and risks. Addressing the potential risks associated with the XEC variant is expected to benefit from interdisciplinary coordination, particularly in regions where genomic surveillance indicates a measurable increase in prevalence. Full article

Background: The long-term immune implications of administering more than four doses of COVID-19 vaccine and the impact of breakthrough infections are not fully understood. Research Design and Methods: We conducted a follow-up cohort study on Japanese healthcare workers who received more than three doses of the BNT162b2 vaccine. We assessed both the anti-SARS-CoV-2 antibody titer and cellular immunity in 429 participants and investigated the numbers, types, and brands of COVID-19 vaccines administered, as well as the episodes of COVID-19 infections after the third dose. Results: Individuals who received three total doses of vaccines with BTI episodes demonstrated higher antibody titers than those who received four total doses of vaccines with no BTIs. The cellular immune responses between these two groups were comparable. Conclusions: These findings suggest that BTIs occurring after the primary series of COVID-19 vaccinations (first to third dose) induced humoral immunity to the spike protein that is greater than that induced by booster doses (fourth or fifth dose) and elicit cellular immunity to the spike protein comparable to that of booster doses. Full article

Tetanus is a life-threatening, vaccine-preventable disease caused by tetanospasmin and tetanolysin, which are potent neurotoxins produced by Clostridium tetani, an anaerobic, spore-forming bacterium. Due to the widespread presence of spores in the environment, the disease cannot be eradicated. However, global tetanus prevention initiatives have contributed to a significant decline in tetanus incidence worldwide. Aiming to present the tetanus trends in Romania, we conducted a retrospective analysis of the tetanus surveillance data. During the study period (2010–2023), 97 cases of tetanus were reported in Romania (median: 6.5; IQR: 5–7) with an average incidence rate of 0.03 per 100,000 inhabitants (95% CI: 0.02–0.04; range: 0.01–0.09). The highest incidence rates were recorded among people aged 1 to 14 years old (0.09 per 100,000 inhabitants, 95% CI: 0.06–0.13; range: 0.00–0.20), male (0.05 per 100,000 inhabitants; 95% CI: 0.03–0.06; range: 0.03–0.12), and from rural areas (0.05 per 100,000 inhabitants; 95% CI: 0.03–0.08; range: 0.01–0.17). A decline in the number of tetanus cases of 7% by year was observed, which is supported by the statistical analysis showing a p-value of 0.005 (IRR: 0.93; 95% CI: 0.88–0.98). However, the same decline in tetanus incidence was not supported by the statistical analysis (IRR: 0.93; 95% CI: 0.44–1.98; p = 0.9). Forty-seven tetanus deaths were recorded, with an average case fatality ratio of 42% (95% CI: 25.62–57.92; range: 0–100), showing a decreasing trend of 9% by year (IRR: 0.91; 95% CI: 0.89–0.93). Although the annual number of tetanus cases in Romania has shown a slight downwards trend, its situation has remained relatively stable, as shown by the tetanus incidence. Moreover, the case fatality rate continues to be high. Therefore, our study emphasizes the importance of achieving high vaccination uptake among children and adolescents, raising awareness of the importance of booster doses in adults, and improving the management of tetanus-prone wounds. Full article

Background: Starting in early 2022, SARS-CoV-2 Omicron has driven large outbreaks in China, a predominantly infection-naive population with high inactivated vaccine coverage. This unique context provided a substantially less-confounded opportunity to evaluate how vaccination, public health, and social measures influenced severity. Methods: We systematically reviewed 86 studies (224 severity estimates) published from 2022 to 2024, reporting symptom and clinical severity outcomes (fever, cough, and sore throat; symptomatic, severe/critical, and fatal illness) of Omicron infections in China. Using meta-regression, we evaluated the associations of study setting, age group, vaccination status, predominant subvariants, and Oxford COVID-19 Government Response Tracker (OxCGRT) indices, including the Government Response Index (GRI), Containment and Health Index (CHI), and the Stringency Index (SI), with infection outcomes, adjusting for key confounders. Results: We found the primary or booster series of inactivated vaccines conferred strong protection against severe/critical illness (pooled relative risk (RR) 0.17 [95% CI: 0.09–0.33]) but did not reduce symptom frequency (RR 0.99 [95% CI: 0.95–1.02]). Each 10-unit increase in GRI or CHI was associated with 7% (95% CI: 1–12%) and 6% (95% CI: 1–10%) lower odds of symptomatic infection and 3% (95% CI: 1–4%) lower odds of severe/critical illness. Later subvariants (BA.5, BF.7, and XBB) showed 24–38% higher odds of upper respiratory symptoms versus BA.1. Conclusions: The data collection context significantly impacted severity estimates, with higher estimates from emergency hospitals. Overall, inactivated vaccines provided strong protection against severe/critical outcomes while stringent public health measures were associated with lower severity. Our findings underscore the importance of consistent and standardized protocols to produce reliable estimates of SARS-CoV-2 severity in evolving epidemiological contexts. Full article

Background/Objectives: Adult vaccination remains suboptimal, particularly among older adults and individuals with chronic conditions. Hospitals represent a strategic setting for improving vaccination coverage among these high-risk populations. This systematic review and meta-analysis evaluated hospital-based interventions aimed at enhancing vaccine uptake in adults aged ≥60 years or 18–64 years with at-risk medical conditions. Methods: We conducted a systematic review and meta-analysis following PRISMA and MOOSE guidelines. Searches in PubMed, EMBASE, and Scopus identified studies published in the last 10 years evaluating hospital-based interventions reporting vaccination uptake. The risk of bias was assessed using validated tools (NOS, RoB 2, ROBINS-I, QI-MQCS). A meta-analysis was conducted for categories with ≥3 eligible studies reporting pre- and post-intervention vaccination coverage in the same population. Results: We included 44 studies. Multi-component strategies (n = 21) showed the most consistent results (e.g., pneumococcal uptake from 2.2% to 43.4%, p < 0.001). Reminder-based interventions (n = 4) achieved influenza coverage increases from 31.0% to 68.0% and a COVID-19 booster uptake boost of +38% after SMS reminders. Educational strategies (n = 11) varied in effectiveness, with one study reporting influenza coverage rising from 1.6% to 12.2% (+662.5%, OR 8.86, p < 0.01). Standing order protocols increased pneumococcal vaccination from 10% to 60% in high-risk adults. Hospital-based catch-up programs improved DTaP-IPV uptake from 56.2% to 80.8% (p < 0.001). For patient education, the pooled OR was 2.11 (95% CI: 1.96–2.27; p < 0.001, I² = 97.2%) under a fixed-effects model, and 2.47 (95% CI: 1.53–3.98; p < 0.001) under a random-effects model. For multi-component strategies, the OR was 2.39 (95% CI: 2.33–2.44; p < 0.001, I² = 98.0%) with fixed effects, and 3.12 (95% CI: 2.49–3.92; p < 0.001) with random effects. No publication bias was detected. Conclusions: Hospital-based interventions, particularly those using multi-component approaches, effectively improve vaccine coverage in older and high-risk adults. Embedding vaccination into routine hospital care offers a scalable opportunity to reduce disparities and enhance population-level protection. Future policies should prioritize the institutional integration of such strategies to support healthy aging and vaccine equity. Full article

Background: SARS-CoV-2 booster vaccination remains essential to prevent severe COVID-19, particularly in vulnerable populations such as older adults. This study evaluated the durability and dynamics of immune responses following booster vaccination(s) in >65-year-old individuals and examined their association with protection against new infections. Methods: Immune responses were evaluated at 3, 9, and 15 months post-booster, measuring SARS-CoV-2-specific IgG antibodies against spike [IgG(S)] and nucleocapsid [IgG(N)] proteins, neutralizing activity against the Omicron BA.2 variant, and cellular immunity. A subset of participants was tested before booster administration. Regression analyses examined the influence of clinical and immunological factors—including a bivalent fourth dose—on infection risk over time. Results: Booster vaccination significantly enhanced IgG(S) and neutralizing capacity, peaking at 3 months. Although a decline was observed by 9 months, responses remained above baseline. Individuals with prior SARS-CoV-2 infection exhibited higher IgG(S) levels and neutralizing titers, and significantly lower reinfection rates (15%), compared to uninfected individuals. A fourth vaccine dose further increased IgG(S) levels. While neutralizing capacity was not consistently enhanced by the fourth dose, recipients experienced a lower rate of new infections. Immune trajectory analyses revealed that breakthrough infections elicited strong humoral responses comparable to those seen in previously infected individuals, highlighting the role of hybrid immunity. Conclusions: In older adults, booster vaccination induces durable immune responses, with hybrid immunity offering enhanced protection. A fourth dose boosts antibody levels and reduces infection risk, supporting its use in this high-risk group. Continued monitoring is needed to determine the long-term effectiveness of boosters, particularly against emerging variants. Full article

The feline calicivirus, herpesvirus, and panleukopenia viruses are major infections that cause serious diseases in cats; however, current trivalent vaccines have limitations in immune efficacy and their duration of protection. This study assesses the immune-enhancing effects of novel adjuvants (feline IL-15, IL-23, and metabolic modulators) on vaccine responses. Forty mice were randomly assigned to four groups: Group A (composite adjuvants), Group B (metabolic regulatory molecules and Mn adjuvant), Group C1 (Mn adjuvant), and Group C2 (a blank commercial vaccine). The results showed that Group A had significantly higher neutralizing antibody titers against calicivirus post-booster immunization, while both Groups A and B exhibited enhanced antibody responses against the herpesvirus and panleukopenia viruses. Notably, Group A displayed increased proportions of memory T cells, follicular B cells, and activated B cells. These findings suggest that the combination of feline IL-15, IL-23, and metabolic modulators are safe and effective immunoadjuvants for trivalent feline vaccines to promote immune cell differentiation and antibody production, thus representing a promising strategy to optimize vaccine efficacy. Full article

Background: Breakthrough infections (BTIs) continue to occur among healthcare workers (HCWs) despite full COVID-19 vaccination, raising concerns about ongoing vulnerability in this high-risk group. In addition to initial BTIs, breakthrough reinfections (BTRs) have emerged as a challenge, with some HCWs experiencing multiple episodes of infection after vaccination. This study investigated the factors influencing breakthrough infection and reinfection rates among HCWs between January 2021 and December 2022 in Davao City, Philippines. Methods: This retrospective cohort study was conducted using secondary data from the Davao City Epidemiological Surveillance Unit, approved by the Department of Health. This study included 1011 fully vaccinated HCWs from various congressional districts. Results: BTI was observed in all HCWs included in the study. However, BTRs varied across occupational groups: medical technologists showed the highest reinfection rate (22.37%), followed by physicians (13.48%), and nurses/nurse aides (10.14%). Booster vaccination significantly reduced BTRs (5.83% vs. 11.18%, p = 0.0267). Occupation and institutional type were significant factors, with higher rates reported by physicians and in public hospitals (p = 0.0002 and p = 0.0041, respectively). The vaccine manufacturer, sex, age, and booster type showed no significant differences. Conclusion: These findings highlight the importance of targeted interventions for high-risk HCWs and emphasize the effectiveness of the booster vaccination. Full article

Virus-like nanoparticles (VNPs) based on Moloney murine leukemia virus represent a well-established platform for the expression of heterologous molecules such as cytokines, cytokine receptors, peptide MHC (pMHC) and major allergens, but their application for inducing protective anti-viral immunity has remained understudied as of yet. Here, we variably fused the wildtype SARS-CoV-2 spike, its receptor-binding domain (RBD) and nucleocapsid (NC) to the minimal CD16b-GPI anchor acceptor sequence for expression on the surface of VNP. Moreover, a CD16b-GPI-anchored single-chain version of IL-12 was tested for its adjuvanticity. VNPs expressing RBD::CD16b-GPI alone or in combination with IL-12::CD16b-GPI were used to immunize BALB/c mice intramuscularly and subsequently to investigate virus-specific humoral and cellular immune responses. CD16b-GPI-anchored viral molecules and IL-12-GPI were well-expressed on HEK-293T-producer cells and purified VNPs. After the immunization of mice with VNPs, RBD-specific antibodies were only induced with RBD-expressing VNPs, but not with empty control VNPs or VNPs solely expressing IL-12. Mice immunized with RBD VNPs produced RBD-specific IgM, IgG_2a and IgG₁ after the first immunization, whereas RBD-specific IgA only appeared after a booster immunization. Protein/peptide microarray and ELISA analyses confirmed exclusive IgG reactivity with folded but not unfolded RBD and showed no specific IgG reactivity with linear RBD peptides. Notably, booster injections gradually increased long-term IgG antibody avidity as measured by ELISA. Interestingly, the final immunization with RBD–Omicron VNPs mainly enhanced preexisting RBD Wuhan Hu-1-specific antibodies. Furthermore, the induced antibodies significantly neutralized SARS-CoV-2 and specifically enhanced cellular cytotoxicity (ADCC) against RBD protein-expressing target cells. In summary, VNPs expressing viral proteins, even in the absence of adjuvants, efficiently induce functional SARS-CoV-2-specific antibodies of all three major classes, making this technology very interesting for future vaccine development and boosting strategies with low reactogenicity. Full article