Search Results (146)

Background: Many new mRNA-based vaccine candidates in liquid mRNA-LNP formulations are under development; however, their stability limitations necessitate frozen storage, posing a significant challenge for long-term storage and transportation. Methods: In this study, an mRNA-LNP rabies vaccine, ABO1005, was prepared, freeze-dried and stored at 2–8 °C for 12-month storage stability evaluation. The immunogenicity, vaccine potency (the NIH method), and protective efficacy of ABO1005 were assessed in mice or dogs and compared to a commercialized inactivated vaccine. Results: Research conducted in mice indicated that the lyophilized vaccine exhibited comparable immunogenicity to its liquid form counterpart. Furthermore, the vaccine candidate elicited a robust humoral response lasting at least 175 days, and the specific antibody titers were not affected by the pre-administration of hyperimmune serum. In comparison to the commercialized inactivated vaccine (HDCV or PVRV), ABO1005 elicited significantly higher levels of humoral and cellular immunity. Vaccine potency testing (NIH) revealed that the potency of ABO1005 at 15 μg/dose was 8.85 IU/dose, which is substantially higher than the standard required for the lot release of rabies vaccines for current human use. In a post-exposure prophylaxis (PEP) study in Beagle dogs, the lyophilized vaccine provided 100% protection for dogs following a two-dose regimen (D0-D7), whereas commercially approved inactivated vaccine offered 83% protection. After storage at 2–8 °C for 12 months, no notable changes were observed in the particle size, encapsulation efficiency, and integrity of mRNA or in the immunogenicity of the lyophilized vaccine. Conclusions: This study successfully developed a formulation and process of freeze-drying for a rabies mRNA vaccine, paving the way for future lyophilized mRNA vaccine development. Full article

Background/Objectives: This study aimed to determine the changes in BVDV (bovine viral diarrhea virus), BoHV-1 (bovine herpesvirus-1), and BRSV (bovine respiratory syncytial virus) antibody levels until weaning in calves who ingested colostrum from vaccinated dairy cattle. Additionally, it aimed to measure the antibody levels induced by the vaccine administered before and after socialization after weaning. Methods: Exposure to respiratory viral and bacterial agents was monitored by PCR analysis using nasal swabs at regular intervals from birth to weaning (pre-colostral and after the 2nd, 7th, 15th, 25th, 35th, 45th, 55th, and 65th days). The levels of colostral BVDV, BoHV-1, and BRSV antibodies were monitored using an enzyme-linked immunosorbent assay (ELISA) at the same intervals from birth to weaning (pre-colostral and after the 2nd, 7th, 15th, 25th, 35th, 45th, 55th, and 65th days). Results: The highest level of maternal antibodies in the blood was detected on day 7. BoHV-1, BVDV, and BRSV antibody levels decreased steadily until weaning by 69.14%, 38%, and 53%, respectively. Conclusions: Vaccination strategies should be planned by considering the presence of maternally derived antibodies and minimizing stress that may negatively affect vaccine titers, thus maximizing vaccine efficacy in calves. Full article

Background/Objectives: Vaccine immunogenicity is often suboptimal in vulnerable populations such as the elderly, infants, and individuals in low- and middle-income countries. One contributing factor may be pre-existing immunomodulatory conditions, including helminth infections. This study investigates the impact of Fasciola hepatica (F. hepatica) derived molecules on the early humoral response to the COVID-19 mRNA vaccine Comirnaty^® in a mouse model. Methods: BALB/c mice were pretreated with a F. hepatica protein extract (FH) or complete Freund’s adjuvant (CFA) prior to vaccination. Cytokine production and antibody responses were assessed at 0, 14, and 21 days post-vaccination (dpv) through serum analysis and ex vivo splenocyte stimulation with the SARS-CoV-2 receptor-binding domain (RBD) or LPS. Results: At 0 dpv, FH-treated mice showed increased serum IL-10, while CFA treatment induced IL-12. FH- but not CFA-treated splenocytes secreted IL-10 upon RBD or LPS stimulation. At 21 dpv, FH-treated mice lacked IFN-γ production but maintained IL-10 and showed elevated IL-4, consistent with a Th2-skewed profile. Although total anti-RBD IgG levels were similar between groups, FH-treated mice exhibited reduced IgG avidity and a higher IgG1/IgG2 ratio. CFA-treated mice showed delayed avidity maturation. Conclusions: Prior exposure to F. hepatica antigens can modulate the early immune response to Comirnaty^®, affecting both cellular activation and antibody quality. This altered response may reflect a reduced early protective capacity of the vaccine, which might need to be considered when designing or evaluating vaccination strategies using mRNA vaccines in helminth-endemic regions. Full article

Background: Infection control is fundamental in dental practice, especially following the COVID-19 pandemic, which highlighted the variability in students’ adherence to disinfection protocols. This study aimed to evaluate the knowledge, attitudes, and practices of the fifth-year dental students at the National and Kapodistrian University of Athens regarding antisepsis and infection control, and to assess the effectiveness of an educational intervention. Methods: A pre-post interventional study was conducted involving two in-person seminars, supplementary e-learning material, and a structured questionnaire administered before and after the intervention. The survey assessed the knowledge, clinical practices, and attitudes toward infection control, including vaccination history and prior exposure incidents. Results: The intervention led to statistically significant improvements in infection control knowledge, especially in risk-based sterilization strategies, disinfectant classification, and PPE use. Students with prior hepatitis B vaccinations and antibody testing demonstrated higher baseline scores and more significant knowledge gains. However, some misconceptions, particularly regarding surface disinfection and prosthetic care, persisted after the intervention. Conclusions: The findings support the effectiveness of structured educational interventions in improving infection control awareness among dental students. Practical, simulation-based training and earlier curriculum integration are recommended to enhance compliance and ensure safe clinical practice. Full article

Community-based serosurveillance for emerging zoonotic viruses can provide a powerful and cost-effective measurement of cryptic spillovers. Betacoronaviruses, including SARS-CoV, SARS-CoV-2 and MERS-CoV, are known to infect bats and can cause severe respiratory illness in humans, yet remain under-surveyed in high-risk populations. This study aimed to determine the seroprevalence of betacoronaviruses in an occupational cohort in contact with bats before and after the emergence of SARS-CoV-2. Serum samples from pre- and post-COVID-19 pandemic were screened using antigen-based multiplex microsphere immunoassays (MMIAs) and a multiplex surrogate virus neutralization test (sVNT). Pre-pandemic samples showed no SARS-CoV-2 antibodies, while post-pandemic samples from vaccinated participants displayed binding and neutralizing antibodies against SARS-CoV-2 and a related bat CoV. Furthermore, one participant (1/237, 0.43%) had persistent antibodies against MERS-CoV in 2017, 2018 and 2021 but was seronegative in 2023, despite reporting no history of traveling abroad or severe pneumonia. The observed sustained antibody levels indicate a possible exposure to MERS-CoV or a MERS-CoV-like virus, although the etiology and clinical relevance of this finding remains unclear. Ongoing surveillance in high-risk populations remains crucial for understanding virus epidemiology and mitigating zoonotic transmission risk. Full article

Background/Objectives: Q-VAX vaccine, approved in Australia, prevents Q fever. However, individuals with prior Coxiella burnetii (Cb) infection have an increased risk of adverse reactions, requiring pre-vaccination screening by an intradermal hypersensitivity skin test for cell-mediated immune memory and a serological assay for anti-Cb antibodies. The week-long interval for skin test assessment limits efficient vaccination. This study evaluated a standardized interferon-γ release assay (IGRA) as a potential skin test alternative. Methods: Immune assays were compared in Australian populations with different incidences of prior Cb exposure. Cell-mediated immunity was assessed by the Q-VAX skin test and IGRA. Serological status was evaluated with established diagnostic assays. Hypothetical vaccine eligibility decisions using combined IGRA and serology results were compared with actual clinical decisions made using current guidelines. Results: All tests performed better in detecting prior infection than in detecting prior vaccination. Only the IGRA identified all individuals with a known history of Q fever. Agreement between the skin test and IGRA was limited. Moderate agreement was observed between hypothetical vaccine eligibility determinations based on IGRA plus serology results and actual clinical decisions. IGRA-positive but serology- and skin test-negative individuals received Q-VAX without clinically significant side effects, suggesting that elevated IGRA responses alone are not predictive of susceptibility to vaccine reactogenicity. Conclusions: The IGRA is not yet a suitable skin test replacement when assessing eligibility for Q fever vaccination, despite the significant limitations of the latter. We offer recommendations for designing future studies that might allow the development of appropriate guidelines for IGRA use in vaccine eligibility screening. Full article

HIV/AIDS remains a global public health concern, with a high prevalence in sub-Saharan Africa. The President’s Emergency Plan for AIDS Relief (PEPFAR) initiatives, including preexposure prophylaxis (PREP) and postexposure prophylaxis (PEP), significantly reduced HIV infections in South Africa and Nigeria. The suspension of United States (U.S.) foreign aid may impact these preventive measures. Although some emergency aid programs were exempted, uncertainty persists, impacting global health initiatives, especially in South Africa and Nigeria. This study investigates the public health impacts of the United States (U.S.) government’s January 2025 suspension of U.S. foreign aid, focusing on its implications for HIV prevention initiatives, such as PREP and PEP, in South Africa and Nigeria. We comprehensively searched keywords such as PEPFAR, PREP, PEP, HIV infection in South Africa or Nigeria, antiretroviral (ARV) drugs, public healthcare impact, 2025 Trump’s foreign aid withdrawal, titles, and abstracts in Google Scholar, PubMed, and Web of Science. The search results were screened from 500 to 150 included articles based on their relevance and quality assessment for inclusion. The review unveiled that Nigeria maintained a continuous increase in HIV/AIDS-related deaths and new HIV infections from 1990, reaching the climax between 1999 and 2005, showing approximately 110,000 HIV/AIDS-related deaths and 200,000 new HIV infections. Notably, due to the PEPFAR intervention in Nigeria, an improved decrease in both HIV/AIDS-related deaths (45,000) and new HIV infections (75,000) was experienced from 2010 to 2023. South Africa experienced a rapid increase between 1990 and 2003 in both HIV/AIDS-related deaths and new HIV infections, reaching the climax around the early 2000s, with about 520,000 new HIV infections and 260,000 HIV/AIDS-related deaths in 2005. Furthermore, there was a continuous decline from 2005 onwards, with 50,000 HIV/AIDS-related deaths and 150,000 new HIV infections by 2023. Therefore, the suspension of this aid threatens disruptions in ARV therapy, possible increases in HIV transmission, shortages in PREP and PEP, the retrenchment of healthcare workers, the suspension of non-governmental organization activities, and the reversal of gains in vulnerable populations, reversing progress toward the 95-95-95 vision, increasing morbidity and mortality rates and financial strain on healthcare systems in these two countries. We recommend proactive measures, such as increased budget allocations for healthcare reforms, exploring local vaccine and health product development and diversifying funding sources in Nigeria, and implementing universal healthcare coverage for South Africans to mitigate the adverse consequences of aid withdrawal. Full article

Background: The MVA-BN vaccine is considered effective for preventing mpox in key populations, based on observational studies, though no randomized trials have yet confirmed its effectiveness. Observational studies published to date rely on retrospective analyses of routine data, often missing information on relevant risk factors for mpox. Methods: Multi-country target trial emulation study with prospective data collection. Between 1 September 2022 and 15 June 2023, we recruited individuals eligible for mpox vaccination based on clinical history and exposure behaviors via healthcare centers and social venues in Spain, Peru, Panama, and Chile. Vaccinated individuals were paired with unvaccinated counterparts matched by mpox risk factors, country, recruitment date, and age. Follow-up continued via periodic surveys until 31 March 2024. The primary endpoint was symptomatic mpox occurrence ≥14 days post-vaccination. Results: The primary analysis included 1028 individuals (514 vaccinated, 514 unvaccinated) with a median follow-up time of 9.3 months (IQR 4.7–13.7). Mpox occurred in eight participants (0.8%): three vaccinated and five unvaccinated (HR 0.6; 95% CI 0.21–1.70). Adverse reactions were reported by 731 (49.6%) participants, predominantly skin reactions (703/1475; 47.7%), while systemic reactions occurred in 107 (7.3%). Long-lasting erythema at the injection site was reported in 450/1058 (42.5%) participants, persisting >6 months in 107 of them (23.8%). Conclusions: The low incidence of mpox during the study period resulted in a limited number of endpoint events, precluding robust conclusions on the efficacy of the MVA-BN vaccine as pre-exposure prevention for mpox. However, our analysis, which accounted for key confounders such as exposure behaviors, yielded results consistent with previous studies suggesting the effectiveness of the vaccine in the mpox setting. Full article

Rabies remains a significant public health and economic concern in Kazakhstan, particularly in rural livestock-farming communities. This study aimed to assess the knowledge, attitudes, and practices (KAPs) related to rabies among livestock farmers in the Aktobe and Oral regions of West Kazakhstan. A cross-sectional survey was conducted between April and August 2022, involving 688 randomly selected participants. The data were collected through structured interviews and analyzed using descriptive and inferential statistics. The findings revealed that 89% of respondents were aware of rabies, yet significant knowledge gaps existed regarding clinical signs, transmission, and prevention. While 87% recognized the importance of rabies vaccination in dogs, 81% were unaware of pre-exposure prophylaxis (PrEP) for cattle, and 72% lacked knowledge of PrEP for humans. Awareness of the post-exposure prophylaxis (PEP) regimen was significantly higher in the Aktobe region (p < 0.002). Attitudinal differences were observed, with the Oral region participants exhibiting more favorable perceptions of rabies control programs (p < 0.01). Additionally, the χ² test revealed that the proportion of female respondents (p < 0.02), those with school-aged dependents (p < 0.003), respondents owning both exotic and indigenous cattle breeds (p < 0.002), and those possessing more than five cattle (p < 0.025) was statistically different in the Oral region. Practices such as free grazing, lack of protective equipment use, and improper carcass disposal were identified as potential risk factors for rabies transmission. This study highlights the need for targeted educational initiatives to improve rabies awareness and promote safer livestock management practices. Enhancing veterinary surveillance, strengthening community engagement, and expanding vaccination efforts could mitigate rabies transmission risks. Full article

Insect-borne viruses may account for a significant proportion of non-malaria and non-bacterial febrile illnesses in Liberia. Although the presence of many arthropod vectors has been documented, the collective burden of arbovirus infections and baseline pre-existing immunity remains enigmatic. Our goal was to determine the seroprevalence of arbovirus exposure across the country using a resource-sparing, multiplex immunoassay to determine IgG responses to immunodominant antigens. 532 human serum samples, from healthy adults, collected from 10 counties across Liberia, were measured for IgG reactivity against antigens of eight common flavi-, alpha-, and orthobunya/nairoviruses suspected to be present in West Africa. Approximately 32.5% of our samples were reactive to alphavirus (CHIKV) E2, ~7% were reactive separately to West Nile (WNV) and Zika virus (ZIKV) NS1, while 4.3 and 3.2% were reactive to Rift Valley Fever virus (RVFV) N and Dengue virus-2 (DENV-2) NS1, respectively. Altogether, 21.6% of our samples were reactive to ≥1 flavivirus NS1s. Of the CHIKV E2 reactive samples, 8.5% were also reactive to at least one flavivirus NS1, and six samples were concurrently reactive to antigens of all three arbovirus groups, suggesting a high burden of multiple arbovirus infections for some participants. These insights suggest the presence of these four arbovirus families in Liberia with low and moderate rates of flavi- and alphavirus infections, respectively, in healthy adults. Further confirmational investigation, such as mosquito surveillance or other serological tests, is warranted and should be conducted before initiating additional flavivirus vaccination campaigns. The findings of these studies can help guide healthcare resource mobilization, vector control, and animal husbandry practices. Full article

The current clinical management of SARS-CoV-2 disease control and immunity may be not optimal anymore. Reverse transcription polymerase chain reaction (RT-PCR) of genomic viral RNA is broadly used for diagnosis, even though the virus may still be detectable when it is already non-infectious. Regarding serology, commercial assays mostly still rely on ancestral spike detection despite significant changes in the genetic sequence of the current circulating variants. We followed a group of 105 non-vaccinated individuals, measuring their viral shedding until negativity and antibody response up to six months. The mean viral detection period until a negative RT-PCR result was 2.2 weeks when using subgenomic RNA-E as a detection target, and 5.2 weeks when using genomic RNA as a detection target. Our neutralising antibody results suggest that, when challenged against a variant different from the variant of first exposure, commercial immunoassays are suboptimal at predicting the neutralising capacity of sera. Additionally, anti-Alpha and anti-Delta antibodies showed very low cross-reactivity between variants. This study provides insights into viral shedding and immune response in pre-Omicron variants like Alpha and Delta, which have been understudied in the published literature. These conclusions point to potential improvements in the clinical management of SARS-CoV-2 cases in order to organise vaccination campaigns and select monoclonal antibody treatments. Full article

Background/Objectives: Equine herpesvirus type-1 (EHV-1) enters through the upper respiratory tract (URT) and causes respiratory disease, abortions, and myeloencephalopathy in equids. Pre-existing immunity at the viral entry site, especially mucosal IgG4/7 antibodies, has recently been shown to correlate with protection from disease and incomplete viral replication at the URT. Here, we tested whether intramuscular (i.m.) vaccination with a commercial inactivated EHV-1/4 vaccine can induce mucosal antibodies (mucAbs) at the URT. Methods: Adult horses with complete EHV-1 vaccination and/or exposure histories were vaccinated i.m. six times within eight months. Before and after each vaccination, blood and nasal swab samples were obtained. Serum and mucAbs were measured in fluorescent bead-based EHV-1 assays. Results: All horses still had existing EHV-1 specific serum and mucAbs prior to vaccination, which were mainly composed of IgG4/7 antibody isotypes. Serum IgG4/7 significantly increased after the first vaccination and stayed high until the end of the study. An additional short-lasting serum IgG1 response was only induced by the first vaccine application. At the URT, mucAbs increased after five out of six i.m. vaccine injections. Like the systemic antibody response, mucAbs were dominated by IgG4/7 and a small IgG1 increase after the first vaccination. Conclusions: Our data emphasize that robust EHV-1 specific mucAb levels are obtained after i.m. vaccination with the inactivated EHV-1/4 vaccine used here. The findings have important implications for evaluating EHV-1/4 vaccines for their ability to induce and maintain protective mucosal IgG4/7 antibodies. Full article

Rabies is a fatal zoonotic disease and causes about 59,000 human deaths globally every year. Especially, its mortality is almost 100% in cases where the rabies virus has transmitted to the central nervous system. The special virus life cycle and pathogenic mechanism make it difficult for the host immune system to combat rabies viruses. Vaccination including pre-exposure and post-exposure prophylaxis is an effective strategy for rabies prevention. The pre-exposure vaccination is mainly applied for animals and the post-exposure vaccination is the most application for humans. Although rabies vaccines are widely used and seem to be safe and effective, there are some disadvantages, limitations, or challenges affecting vaccine promotion and distribution. Therefore, more effective, convenient, safer, and cheaper rabies vaccines have been developed or are being developed. The development of novel human rabies vaccine is mainly focusing on vaccines based on a purified Vero cell-cultured freeze-dried rabies vaccine (PVRV). PVRV has been demonstrated to be promising to make the rabies vaccine more effective and secure in animal studies or clinical trials. Moreover, mRNA-based vaccines have been shown to have the potential to enhance the safety and efficacy of rabies vaccines for both animal and human uses. Full article

(1) Background: Exposure to blood carries the risk of transmission of many infectious diseases. Healthcare workers (HCWs), including hospital-based medical students, face high and often under-reported rates of exposure to needlestick and sharps injuries. Previous studies have shown that students’ knowledge of infection control varies, highlighting the importance of pre-placement training. This study aims to assess knowledge, attitudes and practices regarding these risks in a population of medical students from Albania. (2) Methods: A validated questionnaire was administered to 134 medical students in an Italian hospital in May 2023. It assessed HBV vaccination status, adherence to infection control practices, knowledge of pathogen transmission, exposure incidents and attitudes towards infected patients. Three additional questions addressed air-borne transmission of tuberculosis and vaccination recommendations for healthcare workers. (3) Results: Most students (64%) reported being aware of occupational exposure risks. While 93% and 87%, respectively, recognised HIV and HBV as blood-borne pathogens, fewer recognised Treponema pallidum (44%). Awareness of post-exposure prophylaxis for HIV was high (85%), but although 75% reported having received training, only 45% felt it was adequate. Statistical analysis revealed an association between knowledge of infection control, awareness of pathogen transmission and understanding of the importance of vaccination. (4) Conclusions: Our study highlights gaps in medical students’ knowledge of occupational infections and highlights the need for improved pre-clerkship education. Improved education could reduce anxiety, ethical issues and misconceptions and promote safer healthcare practices. Full article

This longitudinal study examined how active gastrointestinal (GI) cancer types affect immune responses to SARS-CoV-2, focusing on the ability to neutralize the Omicron variants. Patients with GI cancer (n = 168) were categorized into those with hepatocellular carcinoma, hepatic metastatic GI cancer, non-hepatic metastatic GI cancer, and two control groups of patients with and without underlying liver diseases. Humoral and cellular immune responses were evaluated before and after Omicron antigen exposures. In the pre-Omicron era, humoral SARS-CoV-2 immunity decreased after three antigen contacts without further antigen exposure. While Omicron neutralization was significantly lower than wildtype neutralization (p < 0.01), Omicron infections were yet mild to moderate. Additional Omicron exposures improved IgG levels (p < 0.01) and Omicron neutralization (p < 0.01). However, this effect was significantly less intense in patients with active GI cancer, particularly in patients with pancreaticobiliary neoplasms (PBN; p = 0.04), with underlying immunodeficiency (p = 0.05), and/or under conventional chemotherapy (p = 0.05). Pre-Omicron SARS-CoV-2 immunity prevented severe clinical courses of infections with Omicron variants in patients with GI cancer. However, in patients with PBN, with underlying immunodeficiency, and/or under conventional chemotherapy initial contacts with Omicron antigens triggered only reduced immune responses. Thus, subgroups could be identified for whom booster vaccinations are of special clinical significance. Full article