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Keywords = pre-vaccination levels

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13 pages, 603 KiB  
Article
Adapting Ophthalmology Practices in Puerto Rico During COVID-19: A Cross-Sectional Survey Study
by Surafuale Hailu, Andrea N. Ponce, Juliana Charak, Hiram Jimenez and Luma Al-Attar
Epidemiologia 2025, 6(3), 42; https://doi.org/10.3390/epidemiologia6030042 - 6 Aug 2025
Abstract
Background/Objectives: The COVID-19 pandemic caused pronounced disorder in healthcare delivery globally, including ophthalmology. Our study explores how ophthalmologists in Puerto Rico (PR) altered their practices during the pandemic, confronting obstacles such as resource shortages, evolving public health mandates, and unique socio-economic and [...] Read more.
Background/Objectives: The COVID-19 pandemic caused pronounced disorder in healthcare delivery globally, including ophthalmology. Our study explores how ophthalmologists in Puerto Rico (PR) altered their practices during the pandemic, confronting obstacles such as resource shortages, evolving public health mandates, and unique socio-economic and geographic constraints. The study aims to enhance preparedness for future public health crises. Methods: We conducted descriptive analyses on four online surveys distributed at crucial time points of the pandemic (March 2020, May 2020, August 2020, August 2021) to all practicing ophthalmologists in PR (N ≈ 200), capturing data on closures, patient volume, personal protective equipment (PPE) access, telemedicine use, and financial relief. Results: Survey responses ranged from 41% (n = 81) to 56% (n = 111). By March 2020, 22% (24/111) of respondents closed their offices. By May 2020, 20% (19/93) of respondents maintained a closed office, while 89% (64/72) of open offices reported seeing less than 25% of their usual patient volume. Access to PPE was a challenge, with 59% (65/111) reporting difficulty obtaining N95 masks in March 2020. Telemedicine usage increased initially, peaking in May 2020 and declining in July 2020. By August 2021, all respondents were fully vaccinated and most practices returned to pre-pandemic levels. Overall, 86% (70/81) of respondents found the surveys to be useful for navigating practice changes during the pandemic. Conclusions: PR ophthalmologists showed adaptability during the COVID-19 pandemic to maintain care given limited resources. Guidelines from professional organizations and real time surveys play an important role in future crisis preparedness. Full article
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25 pages, 1925 KiB  
Article
Distinctive Temporal Profiles of Interferon-Stimulated Genes in Natural Infection, Viral Challenge, and Vaccination
by Hongxing Lei
Viruses 2025, 17(8), 1060; https://doi.org/10.3390/v17081060 - 29 Jul 2025
Viewed by 313
Abstract
Interferon (IFN) signaling plays vital roles in host defense against viral infection. However, a variety of observations have been reported in the literature regarding the roles of IFN signaling in COVID-19. Thus, it would be important to reach a clearer picture regarding the [...] Read more.
Interferon (IFN) signaling plays vital roles in host defense against viral infection. However, a variety of observations have been reported in the literature regarding the roles of IFN signaling in COVID-19. Thus, it would be important to reach a clearer picture regarding the activation or suppression of IFN signaling in COVID-19. In this work, regulation of marker genes for IFN signaling was examined in natural infection, viral challenge, and vaccination based on 13 public transcriptome datasets. Three subsets of interferon-stimulated genes (ISGs) were selected for detailed examination, including one set of marker genes for type I IFN signaling (ISGa) and two sets of marker genes for type II IFN signaling (IFN-γ signaling, GBPs for the GBP gene cluster, and HLAd for the HLA-D gene cluster). In natural infection, activation of ISGa and GBPs was accompanied by the suppression of HLAd in hospitalized patients. Suppression of GBPs was also observed in certain critical conditions. The scale of regulation was much greater for ISGa than that of GBPs and HLAd. In addition, the suppression of HLAd was correlated with disease severity, and it took much longer for HLAd to return to the level of healthy controls than that for ISGa and GBPs. Upon viral challenge, the activation of ISGa and GBPs was similar to that of natural infection, while the suppression of HLAd was not observed. Moreover, GBPs’ return to the pre-infection level was at a faster pace than that of ISGa. Upon COVID-19 vaccination, activation was observed for all of these three gene sets, and the scale of activation was comparable for ISGa and GBPs. Notably, it took a much shorter time for GBPs and ISGa to return to the level of healthy controls than that in COVID-19 infection. In addition, the baseline values and transient activation of these gene sets were also associated with subsequent vaccination response. The intricate balance of IFN signaling was demonstrated in mild breakthrough infection, where attenuated response was observed in people with prior vaccination compared to that in vaccine-naïve subjects. Overall, distinctive temporal profiles of IFN signaling were observed in natural infection, viral challenge, and vaccination. The features observed in this work may provide novel insights into the disease management and vaccine development. Full article
(This article belongs to the Section Viral Immunology, Vaccines, and Antivirals)
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12 pages, 3161 KiB  
Article
Evaluation of Poxvirus-Specific Antibody Response in Monkey Poxvirus-Negative and -Positive Cohorts
by Nannan Jia, Lin Ai, Yunping Ma, Chen Hua, Qi Shen, Chen Wang, Teng Li, Yingdan Wang, Yunyi Li, Yin Yang, Chi Zhou, Min Chen, Huanyu Wu, Xin Chen, Lu Lu, Yanqiu Zhou, Jinghe Huang and Fan Wu
Vaccines 2025, 13(8), 795; https://doi.org/10.3390/vaccines13080795 - 27 Jul 2025
Viewed by 344
Abstract
Objectives: Understanding the antibody response in monkeypox virus (MPXV)-infected and uninfected individuals is essential for developing next-generation MPXV vaccines. This study aimed to characterize neutralizing antibody (NAb) and antibody-dependent cellular cytotoxicity (ADCC) responses in both groups, providing insights into immune protection and vaccine [...] Read more.
Objectives: Understanding the antibody response in monkeypox virus (MPXV)-infected and uninfected individuals is essential for developing next-generation MPXV vaccines. This study aimed to characterize neutralizing antibody (NAb) and antibody-dependent cellular cytotoxicity (ADCC) responses in both groups, providing insights into immune protection and vaccine design. Methods: A recombinant vaccinia Tian Tan (VTT) virus was utilized to develop high-throughput luciferase-reporter-based neutralization and ADCC assays. These assays were applied to evaluate the presence and levels of poxvirus-specific antibodies in MPXV-infected and uninfected individuals, including those vaccinated with vaccinia-based vaccines. Results: Poxvirus-specific NAbs were detected in MPXV-negative individuals with prior vaccinia vaccination. However, MSM individuals exhibited significantly lower pre-existing NAb levels than non-MSM individuals, potentially contributing to their higher susceptibility to MPXV infection. In individuals with mild MPXV infection, robust NAb and ADCC responses were observed, regardless of vaccination status. Additionally, HIV-positive individuals demonstrated comparable antibody responses following MPXV infection. Conclusions: These findings highlight the potential role of pre-existing NAbs in MPXV susceptibility and the strong immune response elicited by mild MPXV infection. Further research is needed to determine whether MPXV-specific antibodies mitigate disease progression, which could inform the development of effective MPXV vaccines. Full article
(This article belongs to the Section Human Papillomavirus Vaccines)
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21 pages, 1292 KiB  
Article
Polymorphism in IFNλ Can Impact the Immune/Inflammatory Response to COVID-19 Vaccination in Older CMV-Seropositive Adults
by Ariane Nardy, Fernanda Rodrigues Monteiro, Brenda Rodrigues Silva, Jônatas Bussador do Amaral, Danielle Bruna Leal Oliveira, Érika Donizetti de Oliveira Cândido, Edison Luiz Durigon, Andressa Simões Aguiar, Guilherme Pereira Scagion, Vanessa Nascimento Chalup, Guilherme Eustáquio Furtado, Marina Tiemi Shio, Carolina Nunes França, Luiz Henrique da Silva Nali and André Luis Lacerda Bachi
Vaccines 2025, 13(8), 785; https://doi.org/10.3390/vaccines13080785 - 24 Jul 2025
Viewed by 424
Abstract
Background: Chronic cytomegalovirus (CMV) infection may favor the development of immunosenescence and inflammation that impair vaccine responses, including COVID-19. In addition, the polymorphism of the interferon-lambda gene (IFNλ) affects COVID-19 immune responses in older adults. Objective: We aimed to investigate the impact of [...] Read more.
Background: Chronic cytomegalovirus (CMV) infection may favor the development of immunosenescence and inflammation that impair vaccine responses, including COVID-19. In addition, the polymorphism of the interferon-lambda gene (IFNλ) affects COVID-19 immune responses in older adults. Objective: We aimed to investigate the impact of IFNλ polymorphism (IL28B gene-rs12979860) on the immune/inflammatory response to vaccination with CoronaVac for COVID-19 in older adults who were CMV-seropositive. Methods: Blood samples from 42 CMV-seropositive older adults (73.7 ± 4.5 years) were collected before and 30 days after immunization with a second dose of the CoronaVac vaccine to evaluate the immune/inflammatory response. Results: At genotyping, 20 subjects were homozygous for the C/C alleles (Allele-1 group), 5 were homozygous for the T/T Alleles (Allele-2 group), and 17 were heterozygous (C/T, Alleles-1/2 group). The Allele-1 group showed higher IgG levels for COVID-19 (p = 0.0269) and intermediate monocyte percentage (p = 0.017), in contrast to a lower non-classical monocyte percentage (p = 0.0141) post-vaccination than pre-vaccination. Also, this group showed that IgG levels for CMV were positively associated with a systemic pro-inflammatory state and senescent T cells (CD4+ and CD8+). The Allele-2 group presented higher IFN-β levels at pre- (p = 0.0248) and post-vaccination (p = 0.0206) than the values in the Allele-1 and Alleles-1/2 groups, respectively. In addition, the Allele-2 and Alleles-1/2 groups showed that IgG levels for COVID-19 were positively associated with a balanced systemic inflammatory state. Conclusion: CMV-seropositivity in older adults who had Allele-1 could lead to an unbalanced systemic inflammatory state, which may impair their antibody response to COVID-19 vaccination compared to other volunteer groups. Full article
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15 pages, 1304 KiB  
Article
Correlates of SARS-CoV-2 Breakthrough Infections in Kidney Transplant Recipients Following a Third SARS-CoV-2 mRNA Vaccine Dose
by Miriam Viktov Thygesen, Charlotte Strandhave, Jeanette Mølgaard Kiib, Randi Berg, Malene Söth Andersen, Emma Berggren Dall, Bodil Gade Hornstrup, Hans Christian Østergaard, Frank Holden Mose, Jon Waarst Gregersen, Søren Jensen-Fangel, Jesper Nørgaard Bech, Henrik Birn, Marianne Kragh Thomsen and Rasmus Offersen
Vaccines 2025, 13(8), 777; https://doi.org/10.3390/vaccines13080777 - 22 Jul 2025
Viewed by 268
Abstract
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 [...] Read more.
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
(This article belongs to the Section COVID-19 Vaccines and Vaccination)
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11 pages, 1020 KiB  
Communication
XBB.1.5 COVID-19 mRNA Vaccines Induce Inadequate Mucosal Immunity in Patients with Inflammatory Bowel Disease
by Simon Woelfel, Joel Dütschler, Daniel Junker, Marius König, Georg Leinenkugel, Claudia Krieger, Samuel Truniger, Annett Franke, Seraina Koller, Katline Metzger-Peter, Nicola Frei, STAR SIGN Study Investigators, Werner C. Albrich, Matthias Friedrich, Jan Hendrik Niess, Nicole Schneiderhan-Marra, Alex Dulovic, Wolfgang Korte, Justus J. Bürgi and Stephan Brand
Vaccines 2025, 13(7), 759; https://doi.org/10.3390/vaccines13070759 - 16 Jul 2025
Viewed by 522
Abstract
Background: Mucosal immunity plays a pivotal role in preventing infections with SARS-CoV-2. While COVID-19 mRNA vaccines induce robust systemic immune responses in patients with inflammatory bowel disease (IBD), little is known about their efficacy in the mucosal immune compartment. In this sub-investigation of [...] Read more.
Background: Mucosal immunity plays a pivotal role in preventing infections with SARS-CoV-2. While COVID-19 mRNA vaccines induce robust systemic immune responses in patients with inflammatory bowel disease (IBD), little is known about their efficacy in the mucosal immune compartment. In this sub-investigation of the ongoing STAR-SIGN study, we present the first analysis of mucosal immunity elicited by XBB.1.5 mRNA vaccines in immunocompromised patients with IBD. Methods: IgG and IgA antibodies targeting the receptor-binding domain of the SARS-CoV-2 JN.1 variant were quantified longitudinally in the saliva of IBD patients using the multiplex immunoassay MultiCoV-Ab. Antibody levels were quantified before and 2–4 weeks after vaccination with XBB.1.5 mRNA vaccines. All patients previously received three doses with original COVID-19 vaccines. Results: Mucosal IgG antibodies were readily induced by XBB.1.5 mRNA vaccines (p = 0.0013 comparing pre- and post-vaccination levels). However, mucosal IgA levels were comparable before and after vaccination (p = 0.8233). Consequently, mucosal IgG and IgA antibody levels correlated only moderately before and after immunization (pre-vaccination: r = 0.5294; p = 0.0239; post-vaccination: r = 0.4863; p = 0.0407). Contrary to a previous report in healthy individuals, vaccination did not induce serum IgA in patients with IBD (p = 0.5841 comparing pre- and post-vaccination levels). These data suggest that COVID-19 mRNA vaccines fail to elicit mucosal IgA in patients with IBD. Conclusions: Since mucosal IgA plays a pivotal role in infection control, the lack of IgA induction indicates that patients lack sufficient protection against SARS-CoV-2 infections which warrants the development of mucosal COVID-19 vaccines. Full article
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22 pages, 1028 KiB  
Article
Revisiting Public Trust and Media Influence During COVID-19 Post-Vaccination Era—Waning of Anxiety and Depression Levels Among Skilled Workers and Students in Serbia
by Miljan Adamovic, Srdjan Nikolovski, Stefan Milojevic, Nebojsa Zdravkovic, Ivan Markovic, Olivera Djokic, Slobodan Tomic, Ivana Burazor, Dragoslava Zivkov Saponja, Jasna Gacic, Jelena Petkovic, Snezana Knezevic, Marko Spiler, Snezana Svetozarevic and Ana Adamovic
Behav. Sci. 2025, 15(7), 939; https://doi.org/10.3390/bs15070939 - 11 Jul 2025
Viewed by 405
Abstract
Infectious disease outbreaks amplify the influence of stressors on psychological conditions. The purpose of this study was to analyze the disturbing influence of COVID-19 outbreak-related information and the influence of trust on the Serbian healthcare system and COVID-19 preventive measures on anxiety and [...] Read more.
Infectious disease outbreaks amplify the influence of stressors on psychological conditions. The purpose of this study was to analyze the disturbing influence of COVID-19 outbreak-related information and the influence of trust on the Serbian healthcare system and COVID-19 preventive measures on anxiety and depression. An anonymous online questionnaire assessing the demographic information, disturbance level and causes, and levels of anxiety and depression has been distributed to the participants, divided into student and non-student groups. The non-student group was further divided into healthcare, military, and education workers. Anxiety and depression levels, as well as the level of decreased trust in COVID-19-related preventive measures, were higher among students compared to non-students (p = 0.011). Higher anxiety and depression levels, and higher influence of the COVID-19 outbreak on those levels, were observed in education and healthcare workers, compared to military personnel. Medical doctors reported a higher level of trust in the healthcare system compared to nurses (p = 0.023). Trust in the healthcare system increased more frequently compared to the pre-vaccination period among medical doctors, compared to nurses (p = 0.040). Higher anxiety and depression and lower public trust levels in students and workers in education and the healthcare sector indicate a need to focus on these important society members during public health emergencies. Full article
(This article belongs to the Section Social Psychology)
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39 pages, 1706 KiB  
Systematic Review
Improving Vaccine Coverage Among Older Adults and High-Risk Patients: A Systematic Review and Meta-Analysis of Hospital-Based Strategies
by Flavia Pennisi, Stefania Borlini, Rita Cuciniello, Anna Carole D’Amelio, Rosaria Calabretta, Antonio Pinto and Carlo Signorelli
Healthcare 2025, 13(14), 1667; https://doi.org/10.3390/healthcare13141667 - 10 Jul 2025
Viewed by 575
Abstract
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 [...] Read more.
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
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21 pages, 3801 KiB  
Article
Immunogenicity, Efficacy and Twelve-Month Storage Stability Studies of a Lyophilized Rabies mRNA Vaccine
by Chen Chen, Dandan Ling, Kai Ji, Liang Tang, Xiaojing Zhang, Xishan Lu, Xuemei Leng, Changyao Tan, Hongchao Wu, Wenqiang Pang, Quanren He, Jerry Zhang, Peng Gao, Xiaotao Wang, Linhui Wang and Bo Ying
Vaccines 2025, 13(7), 743; https://doi.org/10.3390/vaccines13070743 - 10 Jul 2025
Viewed by 953
Abstract
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 [...] Read more.
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
(This article belongs to the Special Issue The Development of mRNA Vaccines)
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23 pages, 1777 KiB  
Article
Challenges and Lessons Learned from a Field Trial on the Understanding of the Porcine Respiratory Disease Complex
by Elisa Crisci, Andrew R. Kick, Lizette M. Cortes, John J. Byrne, Amanda F. Amaral, Kim Love, Hao Tong, Jianqiang Zhang, Phillip C. Gauger, Jeremy S. Pittman and Tobias Käser
Vaccines 2025, 13(7), 740; https://doi.org/10.3390/vaccines13070740 - 9 Jul 2025
Viewed by 593
Abstract
Background/Objectives: The porcine respiratory disease complex (PRDC) is a multifaceted, polymicrobial syndrome resulting from a combination of environmental stressors, primary infections (e.g., PRRSV) and secondary infectious agents (viruses and bacteria). PRDC causes severe lung pathology, leading to reduced performance, increased mortality rates, and [...] Read more.
Background/Objectives: The porcine respiratory disease complex (PRDC) is a multifaceted, polymicrobial syndrome resulting from a combination of environmental stressors, primary infections (e.g., PRRSV) and secondary infectious agents (viruses and bacteria). PRDC causes severe lung pathology, leading to reduced performance, increased mortality rates, and higher production costs in the global pig industry. Our goal was to conduct a comprehensive study correlating both the anti-PRRSV immune response and 21 secondary infectious agents with PRDC severity. Methods: To this end, PRRSV-negative weaners were vaccinated with a PRRSV-2 MLV and put into a farm with a history of PRDC. Subsequently, anti-PRRSV cellular and antibody responses were monitored pre-vaccination, at 28 days post vaccination (dpv) and during PRDC outbreak (49 dpv). NanoString was used to quantify 21 pathogens within the bronchoalveolar lavage (BAL) at the time of necropsy (51 dpv). PRRSV-2 was present in 53 out of 55 pigs, and the other five pathogens (PCMV, PPIV, B. bronchiseptica, G. parasuis, and M. hyorhinis) were detected in BAL samples. Results: Although the uncontrolled settings of field trials complicated data interpretation, multivariate correlation analyses highlighted valuable lessons: (i) high weaning weight predicted animal resilience to disease and high weight gains correlated with the control of the PRRSV-2 field strain; (ii) most pigs cleared MLV strain within 7 weeks, and the field PRRSV-2 strain was the most prevalent lung pathogen during PRDC; (iii) all pigs developed a systemic PRRSV IgG antibody response which correlated with IgG and IgA levels in BAL; (iv) the induction of anti-field strain-neutralizing antibodies by MLV PRRSV-2 vaccination was both late and limited; (v) cellular immune responses were variable but included strong systemic IFN-γ production against the PRRSV-2 field strain; (vi) the most detected lung pathogens correlated with PRRSV-2 viremia or lung loads; (vii) within the six detected pathogens, two viruses, PRRSV-2 and PCMV, significantly correlated with the severity of the clinical outcome. Conclusions: While a simple and conclusive answer to the multifaceted nature of PRDC remains elusive, the key lessons derived from this unique study provide a valuable framework for future research on porcine respiratory diseases. Full article
(This article belongs to the Special Issue Vaccines for Porcine Diseases)
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13 pages, 1488 KiB  
Article
Respiratory Syncytial Virus Induces B Cell Activating Factor (BAFF) in Airway Epithelium: A Potential Avenue for Mucosal Vaccine Development
by Wael Alturaiki and Brian Flanagan
Viruses 2025, 17(7), 946; https://doi.org/10.3390/v17070946 - 4 Jul 2025
Viewed by 563
Abstract
Respiratory syncytial virus (RSV) is a major etiological agent of lower respiratory tract infections, particularly among infants and the elderly. Activation of B cells in the mucosa and the production of specific neutralizing antibodies are essential for protective immunity against pulmonary infection. B-cell [...] Read more.
Respiratory syncytial virus (RSV) is a major etiological agent of lower respiratory tract infections, particularly among infants and the elderly. Activation of B cells in the mucosa and the production of specific neutralizing antibodies are essential for protective immunity against pulmonary infection. B-cell activating factor (BAFF) is a critical survival factor for B cells and has been associated with antiviral responses; however, its regulation during RSV infection remains poorly understood. This study examined BAFF regulation in BEAS-2B cells exposed to RSV or IFN-β. The treatments resulted in a progressive increase in gene expression over time, accompanied by higher protein levels. BAFF mRNA peaked at 12 h post-infection and declined by 48 h, coinciding with the release of soluble BAFF protein into the culture supernatant. Pre-treatment with anti-IFN-β antibodies prior to RSV infection reduced both BAFF mRNA and protein levels, indicating that IFN-β plays a regulatory role in BAFF production by airway epithelial cells. Western blot analysis revealed membrane-bound BAFF (~31 kDa) in non-infected cells, with elevated expression at 24 h post-infection. By 48 h, this form was cleaved into a soluble ~17 kDa form, which was detected in the supernatant. Immunostaining further demonstrated reduced surface expression of membrane-bound BAFF in RSV-infected cells compared to uninfected controls, suggesting that RSV infection promotes the cleavage and release of BAFF into the extracellular environment. Additionally, the release of BAFF was not affected by furin convertase inhibition or ER–Golgi transport blockade, indicating a potentially novel cleavage mechanism. Co-culturing BAFF produced by BEAS-2B cells with isolated B cells enhanced B cell viability. Overall, these results indicate that RSV infection stimulates BAFF production in airway epithelial cells through a pathway involving IFN-β, potentially contributing to B cell activation and promoting local antibody-mediated immunity. Understanding this mechanism may offer valuable insights for improving mucosal vaccine strategies and enhancing immunity against respiratory pathogens. Full article
(This article belongs to the Section Viral Immunology, Vaccines, and Antivirals)
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13 pages, 977 KiB  
Article
Field Monitoring of Colostral BVDV-, BoHV-1-, and BRSV-Specific Serum Antibody Levels in Dairy Calves from Birth to Weaning Fed with Pasteurized Colostrum Pools Obtained from Vaccinated Dams
by Veysel Soydal Ataseven, Ufuk Kaya, Müge Doğan, Sultan Şengül, Seda Turan, Fatma Türkarslan Akbaba and İsmail İlker Kocaer
Vaccines 2025, 13(7), 709; https://doi.org/10.3390/vaccines13070709 - 29 Jun 2025
Viewed by 408
Abstract
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 [...] Read more.
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
(This article belongs to the Special Issue Vaccine and Vaccination in Veterinary Medicine)
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13 pages, 465 KiB  
Article
Group B Streptococcus (GBS) Carriage in Pregnant Women: Possible Emergence of Rare Serotypes and Antibiotic Resistance in Neonatal Disease
by Roberta Creti, Monica Imperi, Giovanni Gherardi, Giovanna Alfarone, Ilaria Marani, Caterina Vocale, Alberto Berardi, Serena Truocchio and Francesca Miselli
Microorganisms 2025, 13(7), 1496; https://doi.org/10.3390/microorganisms13071496 - 26 Jun 2025
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Abstract
Maternal vaginal and rectal colonization by Streptococcus agalactiae (group B streptococcus, GBS) is the main risk factor for the development of newborn early-onset GBS disease (GBS-EOD). Much effort is in place for its prevention, including the development of vaccines. Currently, both a hexavalent [...] Read more.
Maternal vaginal and rectal colonization by Streptococcus agalactiae (group B streptococcus, GBS) is the main risk factor for the development of newborn early-onset GBS disease (GBS-EOD). Much effort is in place for its prevention, including the development of vaccines. Currently, both a hexavalent glycoconjugate GBS vaccine against the most prevalent serotypes and a protein subunit vaccine have completed phase two clinical trials. GBS surveillance in both maternal carriage and neonatal disease is therefore important in establishing the coverage of the potential vaccines and in setting up the basis for pre- and post-marketing surveillance. A single-site study was conducted in the years 2020–2021 on the characteristics of 325 GBS strains (serotype distribution; identification of the alpha-like protein family member; and resistance to macrolides, tetracycline, and high-level gentamicin) isolated from the vaginal/rectal site in women in late pregnancy as well as in seven cases of GBS-EOD and one case of GBS-related stillbirth occurring in the same location and time period. The study indicated that the coverage of the developing vaccines was excellent (97.2% for the hexavalent glycoconjugate vaccine and 98.7% for the alpha-like protein subunit vaccine). However, the detection of the serotypes VI, VII, and IX—not covered by current vaccine formulations—accounting for 3.0% of isolates, as well as of negative alpha-like GBS strains from maternal carriage (1.2%), should be closely monitored over time. The high rates of GBS resistance to erythromycin (33.5%) and to clindamycin (29.5% in maternal carriage and 57.1% in GBS-EOD) was mostly due to the ever-increasing spread of the multidrug-resistant ST-17 subclone of serotype III. This finding, along with the newly emerging high-level gentamicin resistance in carriers (4.0%), mainly in serotype IV strains, poses a threat for the continued effectiveness of antibiotic therapy in invasive disease. Full article
(This article belongs to the Section Antimicrobial Agents and Resistance)
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13 pages, 2026 KiB  
Article
Pre-Existing Anti-Inflammatory Immune Conditions Influence Early Antibody Avidity and Isotype Profile Following Comirnaty® Vaccination in Mice
by Mariangeles Castillo, María C. Miraglia, Florencia C. Mansilla, Cecilia P. Randazzo, Leticia V. Bentancor, Teresa Freire and Alejandra V. Capozzo
Vaccines 2025, 13(7), 677; https://doi.org/10.3390/vaccines13070677 - 24 Jun 2025
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Abstract
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 [...] Read more.
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
(This article belongs to the Section Vaccine Advancement, Efficacy and Safety)
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12 pages, 668 KiB  
Article
Troubled Times, Changing Tides: A Seroprevalence Study on Meningococcal Immunity in France Between 2016 and 2024
by Samy Taha, Aude Terrade, Oumar Doucoure, Ala-Eddine Deghmane and Muhamed-Kheir Taha
Vaccines 2025, 13(6), 647; https://doi.org/10.3390/vaccines13060647 - 16 Jun 2025
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Abstract
Background/Objectives: In France, non-pharmaceutical interventions (NPIs) implemented to control COVID-19 led to a significant decline in invasive meningococcal disease (IMD) cases. However, a rebound in cases, particularly for serogroups W and Y, was observed after the gradual lifting of NPIs, raising questions about [...] Read more.
Background/Objectives: In France, non-pharmaceutical interventions (NPIs) implemented to control COVID-19 led to a significant decline in invasive meningococcal disease (IMD) cases. However, a rebound in cases, particularly for serogroups W and Y, was observed after the gradual lifting of NPIs, raising questions about an “immunity gap” due to reduced circulation of the bacteria. During the study period, vaccination against MenC was mandatory from 2018, and vaccination against MenB has been recommended since 2022. Methods: We conducted a retrospective seroepidemiological study using 166 normal sera collected between 2016 and 2024. Anti-Neisseria meningitidis IgG levels were quantified by ELISA using purified capsular polysaccharides for serogroups B, C, W, Y, and X. Samples were categorized into three periods: pre-NPIs (n = 72), during NPIs (n = 33), and post-NPIs (n = 61). Statistical comparisons were performed using Kruskal–Wallis tests for non-parametric data. Results: Our results show a significant decline in anti-serogroup B IgG antibody levels after the lifting of NPIs (p < 0.0001) in line with reduced circulation. Anti-serogroup C IgG antibody levels increased incrementally (p = 0.0003), particularly in those aged 1–4 years, likely reflecting a catch-up in anti-meningococcal C vaccination coverage. Anti-serogroup W IgG antibody levels remained stable, suggesting sustained circulation, but shifted to young children in the post-NPI period, potentially due to a genotypic shift. Anti-serogroup Y IgG antibody levels transiently increased significantly (p < 0.0001) during the NPI period but then decreased back after their lifting. Anti-serogroup X IgG antibody levels remained stable, consistent with its low prevalence and the absence of targeted vaccination. Full article
(This article belongs to the Section Vaccines against Tropical and other Infectious Diseases)
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