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14 pages, 834 KiB  
Review
Immunization as Protection Against Long COVID in the Americas: A Scoping Review
by Gabriela Zambrano-Sánchez, Josue Rivadeneira, Carlos Manterola, Tamara Otzen and Luis Fuenmayor-González
Vaccines 2025, 13(8), 822; https://doi.org/10.3390/vaccines13080822 (registering DOI) - 31 Jul 2025
Abstract
Introduction: Long COVID syndrome is defined as persistent or new symptoms that appear after an acute SARS-CoV-2 infection and last at least three months without explanation. It is estimated that between 10% and 20% of those infected develop long COVID; however, data is [...] Read more.
Introduction: Long COVID syndrome is defined as persistent or new symptoms that appear after an acute SARS-CoV-2 infection and last at least three months without explanation. It is estimated that between 10% and 20% of those infected develop long COVID; however, data is not precise in Latin America. Although high immunization rates have reduced acute symptoms and the pandemic’s impact, there is a lack of evidence of its efficacy in preventing long COVID in the region. Methods: This scoping review followed PRISMA-ScR guidelines. Studies on vaccinated adults with long COVID from Central and South America and the Caribbean were included (Mexico was also considered). A comprehensive search across multiple databases was conducted. Data included study design, participant characteristics, vaccine type, and efficacy outcomes. Results are presented narratively and in tables. Results: Out of 3466 initial records, 8 studies met the inclusion criteria after rigorous selection processes. These studies encompassed populations from Brazil, Mexico, Latin America, and Bonaire, with 11,333 participants, 69.3% of whom were female. Vaccination, particularly with three or more doses, substantially reduces the risk and duration of long COVID. Variability was noted in the definitions and outcomes assessed across studies. Conclusions: This scoping review highlights that SARS-CoV-2 vaccination exhibits potential in reducing the burden of long COVID in the Americas. However, discrepancies in vaccine efficacy were observed depending on the study design, the population studied, and the vaccine regimen employed. Further robust, region-specific investigations are warranted to delineate the effects of vaccination on long COVID outcomes. Full article
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14 pages, 291 KiB  
Article
Assessment of SARS-CoV-2 Infection, Vaccination, and Immunity Status Among a Population of Dentists/Academic Professors in a Clinical Setting: One-Year Findings
by Patricia Manarte-Monteiro, Gabriella Marques, Dina Alves, Mary Duro, Joana Domingues, Sandra Gavinha, Lígia Pereira da Silva and Liliana Teixeira
COVID 2025, 5(8), 120; https://doi.org/10.3390/covid5080120 - 28 Jul 2025
Viewed by 132
Abstract
Background: This study aimed to assess the prevalence of SARS-CoV-2 infection, vaccination, and immune status among a population, both Dentists and University Professors, within a clinical setting at one and at 12 months after COVID-19 vaccination. Methods: A cross-sectional study involving 47 professionals [...] Read more.
Background: This study aimed to assess the prevalence of SARS-CoV-2 infection, vaccination, and immune status among a population, both Dentists and University Professors, within a clinical setting at one and at 12 months after COVID-19 vaccination. Methods: A cross-sectional study involving 47 professionals (aged 27–52) was conducted in the University Fernando Pessoa. Participants completed an online survey on SARS-CoV-2 infection status and vaccination, received and provided plasma samples for serological analysis. The protocol was approved by the UFP-Ethics Committee. Anti-S1-RBD SARS-CoV-2 IgM and IgG antibody titration values (AU/mL) were measured, by enzyme-linked-immunosorbent assay (ELISA), with reactive immunoglobulins (Ig) seropositivity for values ≥1 AU/mL. Results: SARS-CoV-2 infection rate increased from 8.5% in July 2021 to 48.9% in June 2022, with 8.5% experiencing reinfection. Vaccination rate was 91.5% by July 2021 and increased slightly to 93.6% by June 2022; 72.3% of the sample received a third dose. IgG seropositivity increased from 91.5% to 95.7% in June 2022. After one-year, significant associations were found between IgG seropositivity and both participant’s age (p = 0.009; <50 years) and vaccine doses (p = 0.003; 1–3 doses) received. Conclusions: SARS-CoV-2 infection rate, vaccination, and IgG seropositivity rates were high and increased over one year. The age and vaccination status were associated with the immunity status at 12th month follow-up. Findings highlight variability in IgG seroprevalence due to multiple influencing factors, which justifies future studies. Full article
(This article belongs to the Section COVID Clinical Manifestations and Management)
13 pages, 518 KiB  
Article
COVID-19 Vaccination Still Makes Sense: Insights on Pneumonia Risk and Hospitalization from a Large-Scale Study at an Academic Tertiary Center in Italy
by Elena Azzolini, Brenda Lupo Pasinetti, Antonio Voza, Antonio Desai, Michele Bartoletti, Stefano Aliberti and Massimiliano Greco
Microorganisms 2025, 13(8), 1744; https://doi.org/10.3390/microorganisms13081744 - 25 Jul 2025
Viewed by 162
Abstract
COVID-19 vaccines have revolutionized prevention and clinical management by reducing disease severity and mortality. However, their long-term impact on hospitalization is unclear. This retrospective study assessed whether vaccination status, timing, and number of vaccine doses influence the risk of hospitalization and COVID-19 pneumonia [...] Read more.
COVID-19 vaccines have revolutionized prevention and clinical management by reducing disease severity and mortality. However, their long-term impact on hospitalization is unclear. This retrospective study assessed whether vaccination status, timing, and number of vaccine doses influence the risk of hospitalization and COVID-19 pneumonia in a large cohort in Italy, several years after initial vaccine rollout. From 1 October 2023, to 2 February 2024, at Humanitas Research Hospital (Milan) and two affiliates, we recorded age, sex, comorbidities, vaccination status (number of doses and time since last dose), admission type (urgent vs. elective), and pneumonia diagnosis. Baseline health was quantified by the Charlson Comorbidity Index. Among 16,034 admissions (14,874 patients), vaccination data were available for 5743 cases: 40.8% were in the emergency setting and 59.2% were elective. Patients presented with pneumonia in 6.8% of cases. Laboratory results confirmed COVID-19 pneumonia occurred in 43.7% of pneumonia cases, with a 16.9% mortality. Patients with no vaccine dose had a higher proportion of COVID-19 pneumonia, while COVID-19 pneumonia rates were lower in individuals who had received more vaccine doses. There were no significant differences in COVID-19 pneumonia risk by timing of last vaccination. Moreover, hospitalized unvaccinated patients had overall more frequent emergency admissions (57.3%), while patients with three or more doses had about a ~40% emergency admission rate. COVID-19 positivity during hospitalization was highest in unvaccinated patients (90.7%) and declined with vaccination status. Vaccinated patients, especially those with multiple doses, had significantly lower COVID-19 pneumonia rates and emergency admissions. These findings suggest a possible protective effect of vaccination in modifying the clinical presentation and severity of illness among those who are hospitalized and support continued vaccination efforts for high-risk groups to reduce severe adverse outcomes. Full article
(This article belongs to the Special Issue SARS-CoV-2: Infection, Transmission, and Prevention)
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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 228
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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13 pages, 3525 KiB  
Article
Epidemiologic Investigation of a Varicella Outbreak in an Elementary School in Gyeonggi Province, Republic of Korea
by Gipyo Sung, Jieun Jang and Kwan Lee
Children 2025, 12(7), 949; https://doi.org/10.3390/children12070949 - 18 Jul 2025
Viewed by 368
Abstract
Background/Objectives: On 6 June 2023, two varicella cases were reported at a highly vaccinated elementary school in Gyeonggi Province, Republic of Korea. We investigated the outbreak to describe its transmission dynamics; quantify attack rates in school, household, and private-academy settings; and assess [...] Read more.
Background/Objectives: On 6 June 2023, two varicella cases were reported at a highly vaccinated elementary school in Gyeonggi Province, Republic of Korea. We investigated the outbreak to describe its transmission dynamics; quantify attack rates in school, household, and private-academy settings; and assess the impact of coordinated control measures. Methods: A case-series study included 89 teachers and students who had contact with suspected patients. Using case definitions, laboratory tests, questionnaires, and environmental assessments, we evaluated exposures and factors facilitating spread. Results: Varicella developed in 23 of 89 contacts (25.8%); laboratory confirmation was obtained in 2 (8.7% of cases). The mean incubation period was 13 days. Epidemic-curve and network analyses indicated that the outbreak began with a single index case and extended through household contacts and private educational facilities, ultimately involving multiple schools. Conclusions: Breakthrough transmission can occur even when single-dose coverage exceeds 95%, particularly as vaccine-induced immunity may wane over time. Poorly regulated extracurricular facilities, such as private academies, act as bridging hubs that amplify spread across grades and even between schools. For timely detection and control, these venues should be incorporated into routine varicella surveillance, and rapid, coordinated infection-control measures are required across all educational settings. Full article
(This article belongs to the Special Issue Pediatric Infectious Disease Epidemiology)
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26 pages, 3044 KiB  
Article
Optimization of YF17D-Vectored Zika Vaccine Production by Employing Small-Molecule Viral Sensitizers to Enhance Yields
by Sven Göbel, Tilia Zinnecker, Ingo Jordan, Volker Sandig, Andrea Vervoort, Jondavid de Jong, Jean-Simon Diallo, Peter Satzer, Manfred Satzer, Kai Dallmeier, Udo Reichl and Yvonne Genzel
Vaccines 2025, 13(7), 757; https://doi.org/10.3390/vaccines13070757 - 16 Jul 2025
Viewed by 786
Abstract
Background: Modern viral vector production needs to consider process intensification for higher yields from smaller production volumes. However, innate antiviral immunity triggered in the producer cell may limit virus replication. While commonly used cell lines (e.g., Vero or E1A-immortalised cells) are already compromised [...] Read more.
Background: Modern viral vector production needs to consider process intensification for higher yields from smaller production volumes. However, innate antiviral immunity triggered in the producer cell may limit virus replication. While commonly used cell lines (e.g., Vero or E1A-immortalised cells) are already compromised in antiviral pathways, the redundancy of innate signaling complicates host cell optimization by genetic engineering. Small molecules that are hypothesized to target antiviral pathways (Viral Sensitizers, VSEs) added to the culture media offer a versatile alternative to genetic modifications to increase permissiveness and, thus, viral yields across multiple cell lines. Methods: To explore how the yield for a chimeric Zika vaccine candidate (YF-ZIK) could be further be increased in an intensified bioprocess, we used spin tubes or an Ambr15 high-throughput microbioreactor system as scale-down models to optimize the dosing for eight VSEs in three host cell lines (AGE1.CR.pIX, BHK-21, and HEK293-F) based on their tolerability. Results: Addition of VSEs to an already optimized infection process significantly increased infectious titers by up to sevenfold for all three cell lines tested. The development of multi-component VSE formulations using a design of experiments approach allowed further synergistic titer increases in AGE1.CR.pIX cells. Scale-up to 1 L stirred-tank bioreactors and 3D-printed mimics of 200 or 2000 L reactors resulted in up to threefold and eightfold increases, respectively. Conclusions: Addition of single VSEs or combinations thereof allowed a further increase in YF-ZIK titers beyond the yield of an already optimized, highly intensified process. The described approach validates the use of VSEs and can be instructive for optimizing other virus production processes. Full article
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14 pages, 2212 KiB  
Article
Long COVID and Its Impacts: A Case–Control Study in Brazil
by Cristina M. Ruas, Maria Laura Silva, Ana L. G. F. Figueiredo, Amanda P. de Alencar, Samuel de S. Melo, Geovani F. de Castro, Natália V. Carobin, Melina A. Cordeiro, Janete F. R. Aguirre, Amanda F. M. de Oliveira and Adriano de P. Sabino
Biomedicines 2025, 13(7), 1615; https://doi.org/10.3390/biomedicines13071615 - 1 Jul 2025
Viewed by 390
Abstract
Introduction: Long COVID, or post-COVID-19 syndrome, refers to a set of persistent symptoms following SARS-CoV-2 infection without another identifiable cause. Studies indicate that symptoms can last for up to two years and affect multiple body systems. Objective: The objective of this study is [...] Read more.
Introduction: Long COVID, or post-COVID-19 syndrome, refers to a set of persistent symptoms following SARS-CoV-2 infection without another identifiable cause. Studies indicate that symptoms can last for up to two years and affect multiple body systems. Objective: The objective of this study is to compare symptom prevalence between infected individuals pre and post-COVID-19 and non-infected individuals in a population from Southeastern Brazil. Materials and Methods: A case–control study was conducted with participants from the MonitoraCovid program in a university in Brazil. The study included adults who responded to a questionnaire about long COVID symptoms. Data were collected virtually between October 2023 and May 2024. Results: Of the 2886 individuals eligible for analysis, 75.5% reported having been positive for COVID-19. Most participants were vaccinated, with 82.99% receiving two doses. In the pre and post comparison, individuals who had COVID-19 were more likely to report increased symptoms after infection, with 95.5% of assessed conditions worsening, particularly cognitive and respiratory issues. A comparison between those who had and had not been infected with COVID-19 showed that only 6.67% of symptoms were more prevalent in the infected group. The most significant post-COVID-19 symptoms included memory problems, fatigue, and shortness of breath, though some conditions, such as anxiety and sleep disturbances, were less common among those who had COVID-19. Conclusions: The findings reinforce that long COVID significantly impacts cognitive health, highlighting the importance of monitoring previously infected individuals. The study also emphasizes the need for further research in Global South contexts to better understand the long-term implications of COVID-19. Full article
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12 pages, 237 KiB  
Article
COVID-19 Vaccine Experience: Loss of Humoral Response Following Autologous Stem Cell Transplantation in Multiple Myeloma Patients and Positive Effect of Booster Dose
by Uros Markovic, Elvira Scalisi, Giuliana Giunta, Antonella Nardo, Andrea Duminuco, Nunziatina Laura Parrinello, Sara Marino, Valeria Iachelli, Giulio Antonio Milone, Paola Scirè, Gabriella Amato, Federica Galbo, Giuseppe Milone, Emanuele Martorana, Alessandra Romano, Concetta Conticello, Francesco Di Raimondo, Gaetano Moschetti and Daniela Carcò
J. Clin. Med. 2025, 14(13), 4648; https://doi.org/10.3390/jcm14134648 - 1 Jul 2025
Viewed by 350
Abstract
Background/Objectives: This prospective study investigated the impact of high-dose chemotherapy and autologous stem cell transplantation (ASCT) on anti-COVID-19 antibody levels in previously vaccinated multiple myeloma (MM) patients with confirmed antibody response (AR). Methods: All patients underwent at least a two-dose regimen [...] Read more.
Background/Objectives: This prospective study investigated the impact of high-dose chemotherapy and autologous stem cell transplantation (ASCT) on anti-COVID-19 antibody levels in previously vaccinated multiple myeloma (MM) patients with confirmed antibody response (AR). Methods: All patients underwent at least a two-dose regimen mRNA vaccination and later received a high-dose melphalan conditioning regimen and ASCT. Results: Fourteen MM patients with confirmed AR underwent a total of nineteen ASCT reinfusions; their median age was 55 (34–67). The study found a significant and progressive decrease in antibody levels after ASCT, from 311 BAU/mL at baseline to 276 BAU/mL and 188 BAU/mL after one and three months, respectively, with a median anti-COVID-19 antibody level reduction of 39% (range 16–66%) that was statistically significant (p = 0.014) using the Friedman test. However, the third “booster” vaccination post-ASCT improved the humoral response at six months in nine patients (50% response rate) and corrected, at least in part, the negative impact of high-dose chemotherapy (p = 0.597). Despite the antibody decline, three patients who contracted COVID-19 after ASCT experienced mild, outpatient-managed infections, suggesting sufficient immune response. Furthermore, booster doses increased the proportion of high-responders (AR > 500 BAU/mL) post-ASCT from 22% to 55% (5/9 patients) at three and six months, respectively. Conclusions: The study concludes that ASCT negatively affects the humoral response, but booster vaccination can improve it, and residual antibodies may prevent severe COVID-19 in these vulnerable patients. Full article
(This article belongs to the Section Hematology)
24 pages, 312 KiB  
Article
Social Ecological Influences on HPV Vaccination Among Cape Verdean Immigrants in the U. S.: A Qualitative Study
by Ana Cristina Lindsay, Celestina V. Antunes, Aysha G. Pires, Monica Pereira and Denise L. Nogueira
Vaccines 2025, 13(7), 713; https://doi.org/10.3390/vaccines13070713 - 30 Jun 2025
Viewed by 358
Abstract
Background: Human papillomavirus (HPV) is the most common sexually transmitted infection in the United States (U.S.) and a major contributor to several cancers, including cervical, anal, penile, and oropharyngeal cancers. Although a safe and effective vaccine is available, HPV vaccination rates remain suboptimal, [...] Read more.
Background: Human papillomavirus (HPV) is the most common sexually transmitted infection in the United States (U.S.) and a major contributor to several cancers, including cervical, anal, penile, and oropharyngeal cancers. Although a safe and effective vaccine is available, HPV vaccination rates remain suboptimal, particularly among racial, ethnic, and immigrant minority groups. This study explored multiple factors, such as cultural, social, and structural influences, influencing HPV vaccine decision-making among Cape Verdean immigrant parents in the U.S., a population currently underrepresented in HPV research. Methods: Qualitative study using individual, in-depth interviews with Cape Verdean immigrant parents of children aged 11 to 17 years living in the U.S. Interviews were transcribed verbatim and analyzed thematically using the social ecological model (SEM) to identify barriers and facilitators at the intrapersonal, interpersonal, organizational, community, and policy levels. Results: Forty-five Cape Verdean parents (27 mothers, 18 fathers) participated. Fathers were significantly older than mothers (50.0 vs. 41.1 years, p = 0.05). Most were married or partnered (60%), had at least a high school education (84.4%), and reported annual household incomes of US$50,000 or more (66.7%), with no significant gender differences. Nearly all spoke Creole at home (95.6%). Fathers had lower acculturation than mothers (p = 0.05), reflecting less adaptation to U.S. norms and language use. Most parents had limited knowledge of HPV and the vaccine, with gendered beliefs and misconceptions about risk. Only seven mothers (25.9%) reported receiving a provider recommendation; all indicated that their children had initiated vaccination (1 dose or more). Mothers were the primary decision-makers, though joint decision-making was common. Trust in providers was high, but poor communication and the lack of culturally and linguistically appropriate materials limited informed decision-making. Stigma, misinformation, and cultural taboos restricted open dialogue. Trusted sources of information included schools, churches, and Cape Verdean organizations. While parents valued the U.S. healthcare system, they noted gaps in public health messaging and provider engagement. Conclusions: Findings revealed that HPV vaccine uptake and hesitancy among Cape Verdean immigrant parents in the U.S. were influenced by individual beliefs, family dynamics, healthcare provider interactions, cultural norms, and structural barriers. These findings highlight the need for multilevel strategies such as culturally tailored education, community engagement, and improved provider communication to support informed vaccination decisions in this population. Full article
(This article belongs to the Special Issue Vaccine Strategies for HPV-Related Cancers: 2nd Edition)
20 pages, 3846 KiB  
Article
Early to Late VSV-G Expression in AcMNPV BV Enhances Transduction in Mammalian Cells but Does Not Affect Virion Yield in Insect Cells
by Jorge Alejandro Simonin, Franco Uriel Cuccovia Warlet, María del Rosario Bauzá, María del Pilar Plastine, Victoria Alfonso, Fernanda Daniela Olea, Carolina Susana Cerrudo and Mariano Nicolás Belaich
Vaccines 2025, 13(7), 693; https://doi.org/10.3390/vaccines13070693 - 26 Jun 2025
Viewed by 408
Abstract
Background/Objectives: Baculoviruses represent promising gene delivery vectors for mammalian systems, combining high safety profiles with substantial cargo capacity. While pseudotyping with vesicular stomatitis virus G-protein (VSV-G) enhances transduction efficiency, optimal expression strategies during the Autographa californica multiple nucleopolyhedrovirus (AcMNPV) infection cycle remain unexplored. [...] Read more.
Background/Objectives: Baculoviruses represent promising gene delivery vectors for mammalian systems, combining high safety profiles with substantial cargo capacity. While pseudotyping with vesicular stomatitis virus G-protein (VSV-G) enhances transduction efficiency, optimal expression strategies during the Autographa californica multiple nucleopolyhedrovirus (AcMNPV) infection cycle remain unexplored. This study investigates how VSV-G expression timing affects pseudotype incorporation into budded virions (BVs) and subsequent transduction efficacy. Methods: Three recombinant AcMNPV constructs were generated, each expressing VSV-G under distinct baculoviral promoters (ie1, gp64, and p10) and GFP via a CMV promoter. VSV-G incorporation was verified by Western blot, while transduction efficiency was quantified in mammalian cell lines (fluorescence microscopy/flow cytometry) and rat hind limbs. Viral productivity was assessed through production kinetics and plaque assays. Results: All the pseudotyped viruses showed significantly enhanced transduction capacity versus controls, strongly correlating with VSV-G incorporation levels. The p10 promoter drove the highest VSV-G expression and transduction efficiency. Crucially, BV production yields and infectivity remained unaffected by VSV-G expression timing. The in vivo results mirrored the cell culture findings, with p10-driven constructs showing greater GFP expression at low doses (104 virions). Conclusions: Strategic VSV-G expression via very late promoters (particularly p10) maximizes baculoviral transduction without compromising production yields. This study establishes a framework for optimizing pseudotyped BV systems, demonstrating that late-phase glycoprotein expression balances high mammalian transduction with preserved insect-cell productivity—a critical advancement for vaccine vector development. Full article
(This article belongs to the Special Issue Viral Vector-Based Vaccines and Therapeutics)
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23 pages, 4903 KiB  
Article
Highly Effective mRNA-LNP Vaccine Against Respiratory Syncytial Virus (RSV) in Multiple Models
by Huarong Bai, Xueliang Yu, Yue Gao, Qin Li, Baigang Wen and Rongkuan Hu
Vaccines 2025, 13(6), 625; https://doi.org/10.3390/vaccines13060625 - 10 Jun 2025
Viewed by 1488
Abstract
Background: The transmembrane fusion (F) protein of RSV plays important roles in RSV pathogenesis as it mediates the fusion between the virus and the target cell membrane. During the fusion process, the F protein transits from a metastable state (prefusion, preF) to a [...] Read more.
Background: The transmembrane fusion (F) protein of RSV plays important roles in RSV pathogenesis as it mediates the fusion between the virus and the target cell membrane. During the fusion process, the F protein transits from a metastable state (prefusion, preF) to a stable state (postfusion, postF) after the merging of the virus and cell membranes. The majority of highly neutralizing antibodies induced by natural infection or immunization target the preF form, which makes it the preferred antigen for vaccine development. Methods: Here, we designed an effective RSV mRNA vaccine, STR-V003, consisting of mRNA encoding preF protein in lipid nanoparticles (LNPs). The immunogenicity, protection efficacy and toxicity were measured in multiple animal models. Results: STR-V003 demonstrated robust immunogenicity in both mice and cotton rats, inducing high levels of neutralizing antibodies and RSV preF-specific IgG antibodies and significantly reducing the RSV viral loads in the lung and nose tissue of challenged animals. In addition, STR-V003 did not show significant enhancement of lung pathology without causing vaccine-enhanced disease (VED). The repeated dose general toxicology studies and local tolerance studies of STR-V003 were evaluated in rats and non-human primate (NHP). Conclusions: STR-V003 demonstrates a favorable safety profile and induces robust protective immunity against RSV. Full article
(This article belongs to the Special Issue The Development of mRNA Vaccines)
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26 pages, 6162 KiB  
Article
Ethnic Comparisons of Spike-Specific CD4+ T Cells, Serological Responses, and Neutralizing Antibody Titers Against SARS-CoV-2 Variants
by Fani Pantouli, Vanessa Silva-Moraes and Ted M. Ross
Vaccines 2025, 13(6), 607; https://doi.org/10.3390/vaccines13060607 - 4 Jun 2025
Viewed by 1040
Abstract
Background/Objectives: To evaluate how immune responses compare among ethnic groups approximately 2 years after receiving a third dose of COVID-19 vaccine (BNT162b2, mRNA-1273, ChAdOx1or BBIBP-CorV), we tested T cell responses and Spike-specific RBD-antibody titer, and neutralized antibody titer levels utilizing Spectral Flow cytometry, [...] Read more.
Background/Objectives: To evaluate how immune responses compare among ethnic groups approximately 2 years after receiving a third dose of COVID-19 vaccine (BNT162b2, mRNA-1273, ChAdOx1or BBIBP-CorV), we tested T cell responses and Spike-specific RBD-antibody titer, and neutralized antibody titer levels utilizing Spectral Flow cytometry, ELISA, and SARS-CoV-2 pseudotyped-based neutralization assays, respectively. Methods: Forty-four individuals from January–December 2023 were identified within the cohort and were classified into different ethnic backgrounds; Black (N = 13), Asian (N = 14), Caucasian (N = 17). We recognize that the “Asian” group includes diverse subpopulations with distinct genetic and environmental backgrounds, which could not be further stratified due to sample-size limitations. Spike-specific AIM+, CD4+, and CD8+ T cell responses were assessed and evaluated against SARS-CoV-2 variants, including the ancestral Wuhan, Delta, and multiple Omicron subvariants (B1.1529, BA2.86, BA.4/5, and XBB.1). Alongside we tested the RBD-IgG and neutralizing antibody titers against the ancestral Wuhan. Spearman’s correlation analysis was utilized to determine corelative relationships among the AIM+ and CD4+ T cell responses, as well as the RBD-IgG and neutralizing antibody titers. Results: Our results show robust and comparable RBD-IgG and neutralizing antibody titers across all groups, with a significant positive correlation between these two measurements. Significant differences were observed in T-cell activation, with Asian participants exhibiting lower frequencies of Spike-specific CD4+ T cells against SARS-CoV-2 Omicron subvariants and higher frequencies of cytokine-producing CD4+ T cells (TNF-α, IFN-γ, and IL-2) as compared to the Caucasian group. Breakthrough infection status was not fully controlled and may influence these findings. Conclusion: Despite a small sample size and potential confounding by natural infections within our long-time-span sampling, our data suggest persistent cellular and humoral immunity 2 years after vaccination across ethnicities, with notable differences in T cell activation and cytokine profile. These preliminary observations highlight the need for larger, more detailed studies that consider intra-ethnic diversity and hybrid immunity to better understand ethnic differences in COVID-19 vaccine responses. Full article
(This article belongs to the Special Issue 3rd Edition: Safety and Autoimmune Response to SARS-CoV-2 Vaccination)
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9 pages, 1150 KiB  
Communication
The Overlooked Nucleocapsid Response: A Cohort Study of SARS-CoV-2 Vaccines in Brazil
by Fatima de Cássia Evangelista de Oliveira, Ana Carolina Matias Dinelly Pinto, Maria Francilene Souza Silva, Max Moreira Lizano Garcia, Maria da Conceição Rodrigues Fernandes, Gabriela Alexandria Damasceno, Amanda Campelo Lima de Melo, Tamires Cardoso Matsui, Tamiris de Fátima Goebel de Souza, Fernanda Gadelha Severino, Virgínia Angélica Silveira Reis, Caroline Passaes, Fernanda Montenegro de Carvalho Araújo, Luiz Odorico Monteiro de Andrade and Marcela Helena Gambim Fonseca
Pathogens 2025, 14(5), 445; https://doi.org/10.3390/pathogens14050445 - 30 Apr 2025
Viewed by 524
Abstract
SARS-CoV-2 has caused global disruptions, prompting studies on immune responses to COVID-19 vaccines, particularly antibodies against the Spike (S) protein. However, responses to the Nucleocapsid (N) protein remain less explored. This study evaluated whether CoronaVac induces anti-N antibodies, and analyzed antibody dynamics after [...] Read more.
SARS-CoV-2 has caused global disruptions, prompting studies on immune responses to COVID-19 vaccines, particularly antibodies against the Spike (S) protein. However, responses to the Nucleocapsid (N) protein remain less explored. This study evaluated whether CoronaVac induces anti-N antibodies, and analyzed antibody dynamics after a BNT162b2 booster, given that CoronaVac targets both S and N proteins, while BNT162b2 targets only the S protein. Serum samples were collected at multiple intervals post-vaccination. The percentage of participants with positive anti-N antibodies increased from 40.26% to 62.09% after two doses of CoronaVac, but declined over time, reaching 29.07% and 18.87% after the second and third doses, respectively. However, seropositivity rose to 43.48% three months after the booster. Anti-S antibody levels peaked at 31,394 AU/mL after the booster, compared to 723.4 AU/mL after the first dose. These findings indicate that CoronaVac stimulates antibody responses against both S and N proteins. Monitoring antibody dynamics is crucial for optimizing vaccination strategies, particularly for high-risk populations, to help control COVID-19. Full article
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11 pages, 358 KiB  
Article
Vaccine-Induced Humoral and Cellular Response to SARS-CoV-2 in Multiple Sclerosis Patients on Ocrelizumab
by Jelena Drulovic, Olivera Tamas, Neda Nikolovski, Nikola Momcilovic, Vanja Radisic, Marko Andabaka, Bojan Jevtic, Goran Stegnjaic, Milica Lazarevic, Nikola Veselinovic, Maja Budimkic, Sarlota Mesaros, Djordje Miljkovic and Tatjana Pekmezovic
Vaccines 2025, 13(5), 488; https://doi.org/10.3390/vaccines13050488 - 30 Apr 2025
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Abstract
Background/Objectives: The aim of our study was to investigate B cell and T cell responses in people with multiple sclerosis (PwMS) treated with ocrelizumab, a humanized anti-CD20 antibody, who were vaccinated with second and/or booster doses of various vaccine brands against COVID-19. [...] Read more.
Background/Objectives: The aim of our study was to investigate B cell and T cell responses in people with multiple sclerosis (PwMS) treated with ocrelizumab, a humanized anti-CD20 antibody, who were vaccinated with second and/or booster doses of various vaccine brands against COVID-19. Additionally, we detected the outcomes related to COVID-19 in PwMS after vaccination, based on follow-up for at least 12 months. Methods: We enrolled 91 PwMS on ocrelizumab and 42 healthy controls (HCs) in a prospective, single-center study, conducted at the Clinic of Neurology, UCCS, between January 2022 and October 2024. The serological responses were measured using the spike receptor-binding domain (RBD) Architect SARS-CoV-2 IgG Quant kit (Abbot), and cellular responses were measured by quantifying IFN-γ secretion in blood incubated with SARS-CoV-2 antigens. Results: A total of 58.2% (53/91) of PwMS on ocrelizumab and 100% of the HCs (42/42) were seropositive after a second or booster vaccination (p < 0.001), irrespective of the vaccine brand received. Anti-spike antibody levels were significantly lower in PwMS on ocrelizumab compared to the HCs (p < 0.001), again irrespective of the vaccine type. Interferon-γ responses were detected in 95.6% of the PwMS receiving ocrelizumab therapy and 97.6% of HCs after vaccination (p = 0.570). In our cohort, PCR-confirmed SARS-CoV-2 infections after vaccination occurred in a similar proportion of the PwMS (45/91, 49.5%) and HCs (15/32, 46.9%) (p = 0.139). Most of the PwMS (36/45, 79.2%) and HCs (13/15, 87.8%) had COVID-19 of mild severity. Conclusions: PwMS treated with ocrelizumab developed diminished humoral and robust cellular responses following two and three SARS-CoV-2 vaccinations. The obtained immunity after SARS-CoV-2 vaccination may translate into lower incidence and severity of COVID-19. Full article
(This article belongs to the Special Issue Effectiveness and Safety of Vaccines in Special Populations)
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19 pages, 1306 KiB  
Article
Individuals Infected with SARS-CoV-2 Prior to COVID-19 Vaccination Maintain Vaccine-Induced RBD-Specific Antibody Levels and Viral Neutralization Activity for One Year
by Christina S. Mcconney, Devin Kenney, Christina S. Ennis, Erika L. Smith-Mahoney, Maria Jose Ayuso, Jiabao Zhong, Florian Douam, Manish Sagar and Jennifer E. Snyder-Cappione
Viruses 2025, 17(5), 640; https://doi.org/10.3390/v17050640 - 29 Apr 2025
Viewed by 729
Abstract
The effectiveness of multiple COVID-19 vaccinations in individuals with a history of SARS-CoV-2 infection remains unclear; specifically, elucidation of the durability of anti-viral antibody responses could provide important insights for epidemiological applications. We utilized the BU ELISA protocol to measure the circulating SARS-CoV-2 [...] Read more.
The effectiveness of multiple COVID-19 vaccinations in individuals with a history of SARS-CoV-2 infection remains unclear; specifically, elucidation of the durability of anti-viral antibody responses could provide important insights for epidemiological applications. We utilized the BU ELISA protocol to measure the circulating SARS-CoV-2 receptor-binding domain (RBD) and nucleocapsid (N) specific IgG and IgA antibody levels in a cohort of individuals infected with SARS-CoV-2 in the spring of 2020, with the sample collection spanning six months to two years post-symptom onset. Further, we interrogated the neutralization activity of these samples against the ancestral SARS-CoV-2 (WA-1) and Delta and Omicron (BA.1) variants. Consistent with previous studies, we found a more rapid waning of anti-N compared to anti-RBD antibodies in months prior to the first vaccinations. Vaccine-induced antibody responses in individuals previously infected with SARS-CoV-2 were elevated and sustained for more than one year post-vaccination. Similarly, neutralization activity against WA-1, Delta, and Omicron increased and remained higher than pre-vaccination levels for one year after the first COVID-19 vaccine dose. Collectively, these results indicate that infection followed by vaccination yields robust antibody responses against SARS-CoV-2 that endure for one year. These results suggest that an annual booster would stably boost anti-SARS-CoV-2 antibody responses, preventing infection and disease. Full article
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