Search

Background/Objectives: There is no approved human vaccine for Venezuelan equine encephalitis (VEE), a life-threatening disease caused by the VEE virus (VEEV). In previous studies, plasmid DNA encoding the full-length RNA genome of the VEE V4020 vaccine was used for the preparation of experimental live virus VEE vaccines in the plasmid-transfected cell culture. Methods: Here, we used the high-fidelity polymerase chain reaction (PCR) to prepare synthetic, transcriptionally active PCR (TAP) fragments encoding the V4020 genome. Results: TAP fragment initiated the replication of the V4020 live virus vaccine in TAP fragment-transfected cells. A transfection of less than 1 ug of TAP fragment resulted in the replication of the V4020 vaccine virus in CHO cells. Conclusion: We conclude that not only plasmid DNA but also synthetic PCR-generated DNA fragments can be used for the manufacturing of live vaccines for VEEV and, potentially, other viruses. [ABSTRACT FROM AUTHOR]

This study provides a preliminary background for the development of a viral vector vaccine for the dengue virus using genetic material encoded by dengue envelope ferritin nanoparticles. Adenoviruses were generated for the recombinant envelope of dengue virus 2 (DENV2) and the envelope human ferritin heavy chain using a two-vector adenovirus system. The primary immunostimulatory activity of the two viruses was analyzed in mice to determine the effect of envelope ferritin nanoparticles. Transfection of a shuttle vector delivered the target gene and packaging vector carrying the packaging signal, and recombinant adenoviruses (rAds) were generated and purified using an ultracentrifugation method. Transduction efficiencies of the generated adenoviruses were confirmed in A549 cells. Purified adenoviruses (8 × 106 PFU/mL) were immunized intramuscularly into 6 weeks old BALB/c mice. Subsequently, the DENV2-specific IgG titer was evaluated 1 and 4 weeks after immunization. Envelope ferritin-immunized mice showed a significant IgG response compared to envelope-only immunized mice at 1 and 4 weeks after immunization, revealing the persistence of the dengue virus-specific IgG response. This method demonstrated the capability of the viral vector vaccine to be used as a carrier for ferritin nanoparticles, instead of direct immunization with ferritin nanoparticles. [ABSTRACT FROM AUTHOR]

Rabies virus (RABV) is among the first recognized viruses of public health concern and has historically contributed to the development of viral vaccines. Despite these significances, the three-dimensional structure of the RABV virion remains unknown due to the challenges in isolating structurally homogenous virion samples in sufficient quantities needed for structural investigation. Here, by combining the capabilities of cryogenic electron tomography (cryoET) and microscopy (cryoEM), we determined the three-dimensional structure of the wild-type RABV virion. Tomograms of RABV virions reveal a high level of structural heterogeneity among the bullet-shaped virion particles encompassing the glycoprotein (G) trimer-decorated envelope and the nucleocapsid composed of RNA, nucleoprotein (N), and matrix protein (M). The structure of the trunk region of the virion was determined by cryoEM helical reconstruction, revealing a one-start N-RNA helix bound by a single layer of M proteins at an N:M ratio of 1. The N-M interaction differs from that in fellow rhabdovirus vesicular stomatitis virus (VSV), which features two layers of M stabilizing the N-RNA helix at an M:N ratio of 2. These differences in both M-N stoichiometry and binding allow RABV to flex its N-RNA helix more freely and point to different mechanisms of viral assembly between these two bullet-shaped rhabdoviruses. [ABSTRACT FROM AUTHOR]

Recent mumps outbreaks have been observed in vaccinated young adults due to the mumps virus (MuV) of genotype G, whereas the current vaccine is a mixture of two genotype A strains. These outbreaks could be attributed to waning vaccine immunity or the antigenic differences between the HN and F glycoproteins in the vaccine and circulating MuV. These glycoproteins are essential targets for the immune system, and antigenic variations may reduce the recognition of mumps antibodies, rendering the population susceptible to the MuV. We established stable cell lines expressing the MuV glycoproteins to study cross-reactivity between genotype A and genotype G. Cross-reactivity between the genotypes was evaluated via immunofluorescence using patient sera from vaccinated individuals, infected individuals, and vaccinated individuals infected with genotype G. Titer ratios showed that the vaccinated individuals exhibited a titer 3.68 times higher for the HN protein and 2.3 times higher for the F protein when comparing genotype A with genotype G. In contrast, the infected individuals showed a lower titer for genotype A compared with genotype G, at 0.43 and 0.33 for the HN and F proteins, respectively. No difference in titer ratio was observed for individuals vaccinated and subsequently infected with mumps. These findings suggest that antigenic variations between the two genotypes may potentially result in immune escape of the circulating strain, resulting in individuals susceptible to the MuV. [ABSTRACT FROM AUTHOR]

Pancreatic adenocarcinoma represents one of the most challenging malignancies to treat, with dismal survival rates despite advances in therapeutic modalities. Immunotherapy, particularly vaccines, has emerged as a promising strategy to harness the body's immune system in combating this aggressive cancer. This abstract reviews the trials and tribulations encountered in the development of vaccines targeting pancreatic adenocarcinoma. Key challenges include the immunosuppressive tumor microenvironment, the heterogeneity of tumor antigens, and a limited understanding of immune evasion mechanisms employed by pancreatic cancer cells. Various vaccine platforms, including peptide-based, dendritic cell-based, and viral vector-based vaccines, have been explored in preclinical and clinical settings. However, translating promising results from preclinical models to clinical efficacy has proven elusive. In recent years, mRNA vaccines have emerged as a promising immunotherapeutic strategy in the fight against various cancers, including pancreatic adenocarcinoma. We will discuss the potential applications, opportunities, and challenges associated with mRNA vaccines in pancreatic cancer treatment. [ABSTRACT FROM AUTHOR]

In this study, the effect of recombinant porcine interferon alpha (rPoIFNa) on porcine transmissible gastroenteritis virus inactivated vaccine (TGEV IV) in terms of immunological augmentation was examined. Seven experimental piglet groups, including PBS group, rPoIFNa group, inactivated vaccine (IV) alone group, 4.0x104 U rPoIFNa+IV group, 2.0x105 U rPoIFNa+IV group, 1.0x106 U rPoIFNa+IV group, 5.0x106 U rPoIFNa+IV group, were divided. The piglets in each group received a secondary vaccination at 28 days following the initial immunization. By using the ELISA assay, neutralization assay, MTT assay, and flow cytometry, we measured anti-TGEV-specific antibody expressions, neutralization antibodies, as well as lymphocyte proliferation index (Stimulation index, SI), specific IL-4 and IFN-γ production, and T cell subpopulations (CD3+, CD4+, and CD8+). Piglets injected with IV supplemented with rPoIFNa at 1.0x106 U or 5.0x106 U developed significantly higher anti-TGEVspecific and neutralizing antibodies compared to those treated with IV alone. IV therapy with rPoIFNa at 1.0x106 U or 5.0x106 U can boost cellular immunity against TGEV by increasing SI, IL-4, IFN-γ, and the ratio of CD3+, CD4+, and CD8+ cell subgroups. The IV+5.0x106 U rPoIFNa group showed a considerably larger immune increase than the IV+2.0x105 U rPoIFNa group, suggesting that it works in a dose-dependent manner. Therefore, rPoIFNa at 1.0x106 U or 5.0x106 U enhances the immune response against TGEV IV and may function as an immune stimulant. [ABSTRACT FROM AUTHOR]

Vaccines signify one of the economical and reasonable means to prevent and eradicate the important infectious diseases. Conventional vaccines like live attenuated and inactivated vaccines comprise of whole pathogen either in attenuated or killed form. While, new generation vaccines have been designed to elicit immune response by genetically modifying only the nucleic acid portion of that pathogen. These new generation therapeutics include mRNA vaccines, DNA plasmid vaccines, chimeric vaccines and recombinant viral vector-based vaccines. Nucleic acid based vaccines use genetic material itself thus, they are highly stable and potent in nature to induce long-lasting immune response. Amongst these novel vaccine platforms, viral vector-based vaccines is one such emerging field which has proven to be extremely effective and potent. Nowadays, veterinary medicine has also accepted this innovative vectored vaccine platform to develop an effective control strategy against certain important viral diseases of animals. Viral vector-based vaccine uses various DNA and RNA viruses of human or animal origin to carry an immunogenic transgene of target pathogen. These vaccines enhance both humoral and cell mediated immune response without use of any accessory immune-stimulants. Till today, several viruses have been modified to be characterized as vaccine vectors. Currently, large number of research programs are going on to develop vectored vaccines and novel viral vector for veterinary use. In the present review, different kinds of viral vectored vaccines having veterinary importance have been discussed. [ABSTRACT FROM AUTHOR]

Maternal vaccines during pregnancy offer crucial protection against infections for both the pregnant person and their newborn. Vaccines against influenza, pertussis, coronavirus disease 2019, and respiratory syncytial virus are routinely recommended by the Centers for Disease Control and Prevention to safeguard pregnant women and their infants from potentially severe complications. Administering these vaccines during pregnancy helps transfer protective antibodies from the mother to the baby, enhancing immunity during the vulnerable early months of life. Extensive research supports the safety and efficacy of maternal vaccines, with numerous studies demonstrating their protective benefits for both pregnant people and newborns. [ABSTRACT FROM AUTHOR]

Since 2019, COVID disease threats the world. It originated in China, and due to its easy spread characteristics, it spreads quickly among all the countries. As the world faced a new kind of virus, the government could not control its spread, and the fatality rate had also hugely increased. In 2021, the vaccine for the virus was introduced by various countries, which aids in controlling the spread and mortality rate. The mutant form of this virus exhibits high efficiency. So, this study analyzes the effective of COVID vaccines released after 2020 against all COVID variants through the fuzzy superiority and inferiority ranking (SIR) decision-making method. The vaccines and variants are analyzed by the m × n matrix pattern under the fuzzy SIR-integrated weight method. The disease variants are taken as criteria and that are assigned integrated weight based on subjective, objective weight approaches. The intuitionistic fuzzy set-double parameter (IFS-DP) handles the vagueness by strictly including only membership and non-membership functions with the condition 0 ≤ μ ∗ (x) + ν ∗ (x) ≤ 1. As a result, the vaccines Moderna and Covishield are attained top rank and have a high likelihood to combat all the COVID variants compared to other vaccines. The reached outcomes are corroborated through sensitivity and comparative analysis. The sensitivity and comparative studies are measured by increasing the order of IFS-DP and extant fuzzy MCDM methods, respectively. The comparison of these results with those obtained from the proposed method is similar to the sensitivity study, along with minor variations observed in the comparative study. Therefore, the proposed method generates an efficient outcome. Moreover, the testing hypothesis technique is applied to check the efficiency of proposed method. [ABSTRACT FROM AUTHOR]

Background: Varicella-Zoster Virus (VZV) is characterized by its ability to enter a dormant state within the body. When the wild or vaccine virus reactivates, it can lead to herpes zoster (HZ), which infrequently manifests as a neuroinfection. Objectives: The aim of the study was to analyze the clinical manifestations and outcomes associated with VZV reactivation in the CNS in immunocompetent children. Methods: We searched medical databases for case reports using the keywords "zoster", "meningitis", "encephalitis", and "immunocompetent". The inclusion criteria were age below 18 years, any gender, race, and ethnicity, no features or history of immunodeficiency, and confirmation of VZV reactivation through the detection of VZV DNA in the CSF. Patients were categorized into two groups: children experiencing the reactivation of the wild virus and children with the vaccine strain virus. Results: The cohort included six children hospitalized in our hospital and 49 children reported in the literature. In 37 (67%), a wild-type virus was detected, while in 18 (33%), an infection was caused by the vaccine strain. There were no differences in the clinical presentation between the two groups. A typical rash was observed in 32 (58%) children. Approximately 41 of the 55 children (75%) received antiviral treatment. Four patients experienced complications. Conclusions: Neither a history of VZV immunization nor the absence of a skin rash can definitively exclude VZV meningitis. It is important to note that any seemingly healthy child, regardless of recognized risk factors, could develop HZ meningitis. [ABSTRACT FROM AUTHOR]

Inducing T lymphocyte (T-cell) activation and proliferation with specificity against a pathogen is crucial in vaccine formulation. Assessing vaccine candidates' ability to induce T-cell proliferation helps optimize formulation for its safety, immunogenicity, and efficacy. Our in-house vaccine candidates use microparticles (MPs) and nanoparticles (NPs) to enhance antigen stability and target delivery to antigen-presenting cells (APCs), providing improved immunogenicity. Typically, vaccine formulations are screened for safety and immunostimulatory effects using in vitro methods, but extensive animal testing is often required to assess immunogenic responses. We identified the need for a rapid, intermediate screening process to select promising candidates before advancing to expensive and time-consuming in vivo evaluations. In this study, an in vitro overlay assay system was demonstrated as an effective high-throughput preclinical testing method to evaluate the immunogenic properties of early-stage vaccine formulations. The overlay assay's effectiveness in testing particulate vaccine candidates for immunogenic responses has been evaluated by optimizing the carboxyfluorescein succinimidyl ester (CFSE) T-cell proliferation assay. DCs were overlaid with T-cells, allowing vaccine-stimulated DCs to present antigens to CFSE-stained T-cells. T-cell proliferation was quantified using flow cytometry on days 0, 1, 2, 4, and 6 upon successful antigen presentation. The assay was tested with nanoparticulate vaccine formulations targeting Neisseria gonorrhoeae (CDC F62, FA19, FA1090), measles, H1N1 flu prototype, canine coronavirus, and Zika, with adjuvants including Alhydrogel® (Alum) and AddaVax™. The assay revealed robust T-cell proliferation in the vaccine treatment groups, with variations between bacterial and viral vaccine candidates. A dose-dependent study indicated immune stimulation varied with antigen dose. These findings highlight the assay's potential to differentiate and quantify effective antigen presentation, providing valuable insights for developing and optimizing vaccine formulations. [ABSTRACT FROM AUTHOR]

The prevalence of the highly pathogenic avian influenza virus H5N1 in wild birds that migrate all over the world has resulted in the dissemination of this virus across Asia, Europe, Africa, North and South America, the Arctic continent, and Antarctica. So far, H5N1 clade 2.3.4.4.b has reached an almost global distribution, with the exception of Australia and New Zealand for autochthonous cases. H5N1 clade 2.3.4.4.b, derived from the broad-host-range A/Goose/Guangdong/1/96 (H5N1) lineage, has evolved, adapted, and spread to species other than birds, with potential mammal-to-mammal transmission. Many public health agencies consider H5N1 influenza a real pandemic threat. In this sense, we analyzed H5N1 hemagglutinin sequences from recent outbreaks in animals, clinical samples, antigenic prototypes of candidate vaccine viruses, and licensed human vaccines for H5N1 with the aim of shedding light on the development of an H5N1 vaccine suitable for a pandemic response, should one occur in the near future. [ABSTRACT FROM AUTHOR]

As respiratory pathogens, influenza B viruses (IBVs) cause a significant socioeconomic burden each year. Vaccine and antiviral development for influenza viruses has historically viewed IBVs as a secondary concern to influenza A viruses (IAVs) due to their lack of animal reservoirs compared to IAVs. However, prior to the global spread of SARS-CoV-2, the seasonal epidemics caused by IBVs were becoming less predictable and inducing more severe disease, especially in high-risk populations. Globally, researchers have begun to recognize the need for improved prevention strategies for IBVs as a primary concern. This review discusses what is known about IBV evolutionary patterns and the effect of the spread of SARS-CoV-2 on these patterns. We also analyze recent advancements in the development of novel vaccines tested against IBVs, highlighting the promise of computational vaccine design strategies when used to target both IBVs and IAVs and explain why these novel strategies can be employed to improve the effectiveness of IBV vaccines. [ABSTRACT FROM AUTHOR]

Maternal vaccination is a safe and effective means of preventing infection in pregnant women, their fetuses, and infants after birth. Several vaccines are routinely administered in pregnancy as a valuable part of prenatal care with supporting recommendations from national and international health organizations. Fears concerning vaccine safety in pregnancy are pervasive despite sufficient available safety data to support their use, leading to underutilization of maternal immunization. Despite this hesitancy, the field of maternal vaccination is evolving to include more vaccines in the routine prenatal vaccination schedule, including the new RSV vaccine. This review discusses the currently recommended vaccines in pregnancy, evidence for their use, and an overview of ongoing clinical trials investigating prospective vaccines for pregnant women. [ABSTRACT FROM AUTHOR]

Background: In the 2022-2023 global outbreak, the United States and state of Texas recorded a total of 31,277 and 3,085 confirmed monkeypox (Mpox) cases respectively as of November 2023. This study aims to investigate the demographic characteristics and risk factors of Mpox outbreak in Houston and document the epidemiologic control measures implemented with their outcomes. Methods: Houston Health Department received reports of suspected Mpox cases via electronic case reports and laboratory reports from healthcare providers within Houston. These were then investigated and reclassified as either positive or negative using DNA polymerase chain reaction tests. All the reported cases received between May 2022 and January 2023 were included in this study using convenient sampling methods. Descriptive statistics using frequency distribution was used to analyze the sociodemographic, clinical features and travel history of the cases. A two-sided Chi-squared test was used to determine association between Mpox test results and risk factors with significant level set at P < 0.05. Other infection control measures such as community engagement, health education, tracking and contact tracing, vaccination, referrals and laboratory sample logistics support were implemented by the health department. Results: Out of the total of 1,625 suspected persons investigated for Mpox, 724 (44.6%) tested positive. Among the 724 confirmed cases, male was 700 (96.7%), females 20 (2.8%), transgender male 1 (0.1%), transgender female 3 (0.4%). Age groups 30-39 years constituted 43.6%, 18-29 years 27.4%, 40-49 years 18.2%, 50-59 years was 8%. Race distribution of positive cases was Whites 43.4%, African American 38.7%, Asian 1.4%. Risk factors with P < 0.05 included male gender, age groups 30-39 years and 40-49 years, travel history to Mpox endemic areas, recent sexual contact with known or suspected Mpox cases, human immunodeficiency virus seropositivity. Identifying as gay and bisexual were also statistically significant risk factors for Mpox infection. Conclusion: The timely implementation of primary and secondary prevention measures targeted at the most at-risk populations was very effective at curtailing the spread of Mpox infection within the city of Houston. [ABSTRACT FROM AUTHOR]

Severe fever with thrombocytopenia syndrome (SFTS) is a newly identified tick-borne viral hemorrhagic fever caused by Dabie Banda virus (DBV). The virus was first discovered in eastern China in 2009 and is now considered an infectious disease with a mortality rate ranging from 6.3% to 30%. The best strategy for controlling SFTS is to develop effective vaccines. However, no approved vaccines are currently available to prevent this disease, despite the number of extensive and in-depth studies conducted on DBV in the past few years. This review focuses on the structure of DBV and the induced host immune responses which are the fundamental factors in vaccine development, and thoroughly summarizes the current research progress on DBV vaccines. The developing DBV vaccines include protein subunit vaccines, live attenuated vaccines, recombinant virus vector vaccines, and DNA vaccines. At present, almost all candidate vaccines for DBV are in the laboratory development or preclinical stages. There remain challenges in successfully developing clinically approved DBV vaccines. [ABSTRACT FROM AUTHOR]

Replication-defective viral vector vaccines have several advantages over conventional subunit vaccines, including potent antibody responses, cellular responses critical for eliminating pathogen-infected cells, and the induction of highly immunogenic and durable immune responses without adjuvants. The Human papillomavirus (HPV), a microorganism with over 200 genotypes, plays a crucial role in inducing human tumors, with the majority of HPV-related malignancies expressing HPV proteins. Tumors associated with HPV infection, most of which result from HPV16 infection, include those affecting the cervix, anus, vagina, penis, vulva, and oropharynx. In recent years, the development of therapeutic HPV vaccines utilizing viral vectors for the treatment of premalignant lesions or tumors caused by HPV infection has experienced rapid growth, with numerous research pipelines currently underway. Simultaneously, screening for optimal antigens requires more basic research and more optimized methods. In terms of preclinical research, we present the various models used to assess vaccine efficacy, highlighting their respective advantages and disadvantages. Further, we present current research status of therapeutic vaccines using HPV viral vectors, especially the indications, initial efficacy, combination drugs, etc. In general, this paper summarizes current viral vector therapeutic HPV vaccines in terms of HPV infection, antigen selection, vectors, efficacy evaluation, and progress in clinical trials. [ABSTRACT FROM AUTHOR]

New adjuvants that trigger cellular immune responses are urgently needed for the effective development of cancer and virus vaccines. Motivated by recent discoveries that show activation of type I interferon (IFN‐I) signaling boosts T cell immunity, this study proposes that targeting this pathway can be a strategic approach to identify novel vaccine adjuvants. Consequently, a comprehensive chemical screening of 6,800 small molecules is performed, which results in the discovery of the natural compound picrasidine S (PS) as an IFN‐I inducer. Further analysis reveals that PS acts as a powerful adjuvant, significantly enhancing both humoral and cellular immune responses. At the molecular level, PS initiates the activation of the cGAS‐IFN‐I pathway, leading to an enhanced T cell response. PS vaccination notably increases the population of CD8+ central memory (TCM)‐like cells and boosts the CD8+ T cell‐mediated anti‐tumor immune response. Thus, this study identifies PS as a promising candidate for developing vaccine adjuvants in cancer prevention. [ABSTRACT FROM AUTHOR]

Introduction: The Vaccines for Children (VFC) program was established in 1994 to provide recommended vaccines at no cost to eligible children and help ensure that all U.S. children are protected from life-threatening vaccine-preventable diseases. Methods: CDC analyzed data from the 2012–2022 National Immunization Survey-Child (NIS-Child) to assess trends in vaccination coverage with ≥1 dose of measles, mumps, and rubella vaccine (MMR), 2–3 doses of rotavirus vaccine, and a combined 7-vaccine series, by VFC program eligibility status, and to examine differences in coverage among VFC-eligible children by sociodemographic characteristics. VFC eligibility was defined as meeting at least one of the following criteria: 1) American Indian or Alaska Native; 2) insured by Medicaid, Indian Health Service (IHS), or uninsured; or 3) ever received at least one vaccination at an IHS-operated center, Tribal health center, or urban Indian health care facility. Results: Overall, approximately 52.2% of U.S. children were VFC eligible. Among VFC-eligible children born during 2011–2020, coverage by age 24 months was stable for ≥1 MMR dose (88.0%–89.9%) and the combined 7-vaccine series (61.4%–65.3%). Rotavirus vaccination coverage by age 8 months was 64.8%–71.1%, increasing by an average of 0.7 percentage points annually. Among all children born in 2020, coverage was 3.8 (≥1 MMR dose), 11.5 (2–3 doses of rotavirus vaccine), and 13.8 (combined 7-vaccine series) percentage points lower among VFC-eligible than among non–VFC-eligible children. Conclusions and implications for public health practice: Although the VFC program has played a vital role in increasing and maintaining high levels of childhood vaccination coverage for 30 years, gaps remain. Enhanced efforts must ensure that parents and guardians of VFC-eligible children are aware of, have confidence in, and are able to obtain all recommended vaccines for their children. [ABSTRACT FROM AUTHOR]

Marek's disease virus (MDV) integrates its genome into the telomeres of host chromosomes and causes fatal lymphomas in chickens. This integration is facilitated by telomeric repeat sequences (TMRs) at the ends of the viral genome, and is crucial for MDV-induced lymphomagenesis. The SB-1 vaccine virus is commonly used in commercial bivalent vaccines against MDV and also contains TMRs at its ends. Here, we demonstrate that SB-1 efficiently integrates its genome into the chromosomes of latently infected T cells. Deletion of the TMRs from the SB-1 genome did not affect virus replication, but severely impaired virus integration and genome maintenance in latently infected T cells and in chickens. Strikingly, the reduced integration and maintenance of latent SB-1 significantly impaired vaccine protection. Taken together, our data revealed that the TMRs facilitate SB-1 integration and that integration and/or maintenance of the latent viral genome is critical for vaccine protection. [ABSTRACT FROM AUTHOR]

Rift Valley fever (RVF) is an important zoonotic viral disease affecting several species of domestic and wild ruminants, causing major economic losses and dozens of human deaths in various geographical areas of Africa, where it is endemic. Although it is not present in Europe, there is a risk of its introduction and spread linked to globalisation and climate change. At present, the only measure that could help to prevent the disease is vaccination of flocks in areas at risk of RVF. Available live attenuated vaccines are an effective means of controlling the disease, but their use is often questioned due to residual virulence, particularly in susceptible hosts such as pregnant sheep. On the other hand, no vaccine is currently licensed for use in humans. The development of safe and effective vaccines is therefore a major area of research. In previous studies, we selected under selective mutagenic pressure a highly attenuated RVFV 56/74 virus variant called 40Fp8. This virus showed an extremely attenuated phenotype in both wild-type and immunodeficient A129 (IFNARKO) mice, yet was still able to induce protective immunity after a single inoculation, thus supporting its use as a safe, live attenuated vaccine. To further investigate its safety, in this work we have analysed the attenuation level of 40Fp8 in immunosuppressed mice (A129) when administered by the intranasal route, and compared it with other attenuated RVF viruses that are the basis of vaccines in use or in development. Our results show that 40Fp8 has a much higher attenuated level than these other viruses and confirm its potential as a candidate for safe RVF vaccine development. Author summary: Vaccines that use attenuated viruses are highly effective in terms of providing protection, duration, breadth, and quality of the immune response. However, they may pose a risk to immunosuppressed individuals or in certain situations, such as during pregnancy. It is therefore important to analyze the residual virulence of attenuated vaccines to ensure their safety. In this work, we analysed the safety of the RVF virus vaccine variant 40Fp8 developed in our laboratory. We studied its effect on immunodeficient mice and used a more aggressive route of administration such as the intranasal delivery route. To assess the degree of attenuation of 40Fp8, we compared it with other attenuated prototype RVF vaccines. The results clearly demonstrate that 40Fp8 is highly attenuated, and its residual virulence level is extremely low compared to other vaccine viruses tested. [ABSTRACT FROM AUTHOR]

Multivalent live-attenuated or inactivated vaccines are often used to control the bovine viral diarrhea disease (BVD). Still, they retain inherent disadvantages and do not provide the expected protection. This study developed a new vaccine prototype, including the external segment of the E2 viral protein from five different subgenotypes selected after a massive screening. The E2 proteins of every subgenotype (1aE2, 1bE2, 1cE2, 1dE2, and 1eE2) were produced in mammalian cells and purified by IMAC. An equimolar mixture of E2 proteins formulated in an oil-in-water adjuvant made up the vaccine candidate, inducing a high humoral response at 50, 100, and 150 µg doses in sheep. A similar immune response was observed in bovines at 50 µg. The cellular response showed a significant increase in the transcript levels of relevant Th1 cytokines, while those corresponding to the Th2 cytokine IL-4 and the negative control were similar. High levels of neutralizing antibodies against the subgenotype BVDV1a demonstrated the effectiveness of our vaccine candidate, similar to that observed in the sera of animals vaccinated with the commercial vaccine. These results suggest that our vaccine prototype could become an effective recombinant vaccine against the BVD. [ABSTRACT FROM AUTHOR]

The highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) poses a significant threat to the global swine industry. Vaccination is a preventive measure against viral infections. However, the use of vaccines in livestock healthcare programs faces the challenge of safety and delayed immune responses. Earlier studies have shown the potential of modified Bazhen powder as an immunomodulator with significant biological properties, but its effect on vaccines against HP-PRRSV is yet to be studied. This study elucidated how modified Bazhen powder could improve the safety and efficacy of the conventional PRRSV vaccine by evaluating T-cell responses, antibody levels, clinical symptoms, levels of viremia, organ health, and cytokine production. The results revealed that the oral application of modified Bazhen powder in combination with PRRS vaccination improved both cellular and humoral immunity, accelerated viremia clearance, improved lung injury scores, and reduced viral load in the tonsils. The modified Bazhen powder also effectively reduced inflammatory responses following a PRRSV challenge. These findings further highlight the pharmacological properties of modified Bazhen powder as a potential oral immunomodulatory agent that could enhance vaccine efficacy and ensure broad-spectrum protection against HP-PRRSV in pigs. [ABSTRACT FROM AUTHOR]

One major limitation of effective vaccine delivery is its dependency on a robust cold chain infrastructure. While Vesicular stomatitis virus (VSV) has been demonstrated to be an effective viral vaccine vector for diseases including Ebola, its −70 °C storage requirement is a significant limitation for accessing disadvantaged locations and populations. Previous work has shown thermal stabilization of viral vaccines with a combination of pullulan and trehalose (PT) dried films. To improve the thermal stability of VSV, we optimized PT formulation concentrations and components, as well as drying methodology with enhanced vacuum drying. When formulated in PT films, VSV can be stored for 32 weeks at 4 °C with less than 2 log PFU loss, at 25 °C with 2.5 log PFU loss, and at 37 °C with 3.1 log PFU loss. These results demonstrate a significant advancement in VSV thermal stabilization, decreasing the cold chain requirements for VSV vectored vaccines. [ABSTRACT FROM AUTHOR]

Lassa fever virus (LASV), a member of the Arenavirus family, is the etiological agent of Lassa fever, a severe hemorrhagic disease that causes considerable morbidity and mortality in the endemic areas of West Africa. LASV is a rodent-borne CDC Tier One biological threat agent and is on the World Health Organization's (WHO) Priority Pathogen list. Currently, no FDA-licensed vaccines or specific therapeutics are available. Here, we describe the efficacy of a deactivated rabies virus (RABV)-based vaccine encoding the glycoprotein precursor (GPC) of LASV (LASSARAB). Nonhuman primates (NHPs) were administered a two-dose regimen of LASSARAB or an irrelevant RABV-based vaccine to serve as a negative control. NHPs immunized with LASSARAB developed strong humoral responses to LASV-GPC. Upon challenge, NHPs vaccinated with LASSARAB survived to the study endpoint, whereas NHPs in the control group did not. This study demonstrates that LASSARAB is a worthy candidate for continued development. [ABSTRACT FROM AUTHOR]

Chikungunya virus (CHIKV), a single-stranded RNA virus transmitted by Aedes mosquitoes, poses a significant global health threat, with severe complications observed in vulnerable populations. The only licensed vaccine, IXCHIQ, approved by the US FDA, is insufficient to address the growing disease burden, particularly in endemic regions lacking herd immunity. Monoclonal antibodies (mAbs), explicitly targeting structural proteins E1/E2, demonstrate promise in passive transfer studies, with mouse and human-derived mAbs showing protective efficacy. This article explores various vaccine candidates, including live attenuated, killed, nucleic acid-based (DNA/RNA), virus-like particle, chimeric, subunit, and adenovirus vectored vaccines. RNA vaccines have emerged as promising candidates due to their rapid response capabilities and enhanced safety profile. This review underscores the importance of the E1 and E2 proteins as immunogens, emphasizing their antigenic potential. Several vaccine candidates, such as CHIKV/IRES, measles vector (MV-CHIK), synthetic DNA-encoded antibodies, and mRNA-lipid nanoparticle vaccines, demonstrate encouraging preclinical and clinical results. In addition to identifying potential molecular targets for antiviral therapy, the study looks into the roles played by Toll-like receptors, RIG-I, and NOD-like receptors in the immune response to CHIKV. It also offers insights into novel tactics and promising vaccine candidates. This article discusses potential antiviral targets, the significance of E1 and E2 proteins, monoclonal antibodies, and RNA vaccines as prospective Chikungunya virus vaccine candidates. [ABSTRACT FROM AUTHOR]

The present study aimed to generate 3D spheroid cultures from three rainbow trout (RTE, RTK and RTS) cell lines by simple and reproducible methods and evaluated them for the propagation of fish viral pathogen for the first time. The 3D spheroids were generated in the present study by scaffold-free method using 3D-orbital shaker. The growth of spheroids was documented on each day until 15 days and their viability was assessed by using AO/EB and Hoechst 33258 fluorescent staining under bright field microscope. The successfully generated RTK spheroids (RTKs) from the RTK cells were further used for the propagation of SJNNV virus in direct comparison of viral growth with conventional 2D monolayer culture of RTK cell line. Immunofluorescent staining confirms the expression of SJNNV major capsid protein in infected RTK spheroid earlier than the RTK monolayer. The samples collected from both RTK spheroid and RTK monolayer at different days of post infection was confirmed by RT-PCR and their viral copy numbers found high in RTK spheroid while quantified by qRT-PCR. Further, SJNNV major capsid protein was confirmed by western blot and ELISA. The viral load obtained using RTK spheroid was found to be high when compared to the monolayer and this study suggests that the spheroid generated from RTK cells is more suitable in vitro tool that can be used for propagation of fish viral pathogens in large-scale for production of whole virus vaccine. [ABSTRACT FROM AUTHOR]

African swine fever (ASF) is a highly contagious and severe hemorrhagic transboundary swine viral disease with up to a 100% mortality rate, which leads to a tremendous socio-economic loss worldwide. The lack of safe and efficacious ASF vaccines is the greatest challenge in the prevention and control of ASF. In this study, we generated a safe and effective live-attenuated virus (LAV) vaccine candidate VNUA-ASFV-LAVL3 by serially passaging a virulent genotype II strain (VNUA-ASFV-L2) in an immortalized porcine alveolar macrophage cell line (3D4/21, 50 passages). VNUA-ASFV-LAVL3 lost its hemadsorption ability but maintained comparable growth kinetics in 3D4/21 cells to that of the parental strain. Notably, it exhibited significant attenuation of virulence in pigs across different doses (103, 104, and 105 TCID50). All vaccinated pigs remained healthy with no clinical signs of African swine fever virus (ASFV) infection throughout the 28-day observation period of immunization. VNUA-ASFV-LAVL3 was efficiently cleared from the blood at 14–17 days post-infection, even at the highest dose (105 TCID50). Importantly, the attenuation observed in vivo did not compromise the ability of VNUA-ASFV-LAVL3 to induce protective immunity. Vaccination with VNUA-ASFV-LAVL3 elicited robust humoral and cellular immune responses in pigs, achieving 100% protection against a lethal wild-type ASFV (genotype II) challenge at all tested doses (103, 104, and 105 TCID50). Furthermore, a single vaccination (104 TCID50) provided protection for up to 2 months. These findings suggest that VNUA-ASFV-LAVL3 can be utilized as a promising safe and efficacious LAV candidate against the contemporary pandemic genotype II ASFV. [ABSTRACT FROM AUTHOR]

• Activity retention of an enveloped virus through spray drying and lyophilization. • Enhanced thermal stability of an enveloped virus upon drying for vaccine and gene therapy applications. • Characterization of morphology, T g , and crystallinity of spray dried and lyophilized viral preparations. Enveloped viruses are attractive candidates for use as gene- and immunotherapeutic agents due to their efficacy at infecting host cells and delivering genetic information. They have also been used in vaccines as potent antigens to generate strong immune responses, often requiring fewer doses than other vaccine platforms as well as eliminating the need for adjuvants. However, virus instability in liquid formulations may limit their shelf life and require that these products be transported and stored under stringently controlled temperature conditions, contributing to high cost and limiting patient access. In this work, spray-drying and lyophilization were used to embed an infectious enveloped virus within dry, glassy polysaccharide matrices. No loss of viral titer was observed following either spray-drying (at multiple drying gas temperatures) or lyophilization. Furthermore, viruses embedded in the glassy formulations showed enhanced thermal stability, retaining infectivity after exposure to elevated temperatures as high as 85 °C for up to one hour, and for up to 10 weeks at temperatures as high as 30 °C. In comparison, viruses in liquid formulations lost infectivity within an hour at temperatures above 40 °C, or after incubation at 25 °C for longer periods of time. [ABSTRACT FROM AUTHOR]

Objective: The 2022 global mpox outbreak disproportionately impacted people living with HIV. This review explores recent evidence on mpox in this group, focusing on clinical presentation, complications, treatment modalities and vaccine strategies. Recent findings: Recent studies have suggested that people with HIV diagnosed with mpox have a greater risk of proctitis and hospitalization compared with people without HIV. In addition, those with advanced immunosuppression face an elevated risk of severe mpox infection, which can lead to mortality. Comprehensive and prompt supportive care using antiretrovirals and mpox antivirals is crucial in this group. Although results from randomized clinical trials are still forthcoming, recent studies suggest that early initiation of tecovirimat can prevent disease progression in people with HIV. The non‐replicative attenuated smallpox vaccine is well tolerated and effective in preventing monkeypox virus infections in people with HIV. Further studies are needed regarding long‐term vaccine effectiveness for this population. Conclusion: Evaluating the risk of severe mpox in people living with HIV requires assessing the level of immune suppression and viral control. Universal access to vaccination is imperative to prevent the resurgence of future outbreaks. [ABSTRACT FROM AUTHOR]

Objective: This cross-sectional-survey-based study aimed to investigate the severity of side-effects from Coronavirus disease (COVID-19) mRNA (Pfizer, Moderna), viral vector DNA (Oxford-AstraZeneca, J&J/Janssen), inactivated virus (Sinopharm, Sinovac), and other vaccines among healthcare workers (HCWs) in Saudi Arabia, focusing on their impact on work attendance. Methods: A total of 894 HCWs residing in Saudi Arabia participated in this study from March 2023 to May 2023. Participants completed an online questionnaire assessing demographic information, vaccination status, comorbidities, vaccine side-effects, and missed work information after vaccination. Descriptive statistics and chi-square tests were used for data analysis. Results: The majority of participants were female (83.7%) and aged 25–34 years (42.8%). Most participants were predominantly vaccinated with mRNA vaccines. Common side-effects included pain at the injection site, fatigue, fever, and chills. However, no significant association was found between vaccine type, side-effects, and work absenteeism. While demographic factors such as age and healthcare profession did not influence work absenteeism, variations were observed among different racial groups. Conclusion: COVID-19 vaccination among HCWs in Saudi Arabia is associated with common side-effects, but their impact on work attendance is not significant. Understanding these implications can inform strategies to support the healthcare workforce and mitigate the impact on patient care and staffing during the ongoing COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus (RSV) infection is an acute respiratory infection caused by RSV. It occurs worldwide, and for over 50 years, several attempts have been made to research and develop vaccines to prevent RSV infection; effective preventive vaccines are eagerly awaited. The RSV fusion (F) protein, which has gained attention as a vaccine antigen, causes a dynamic structural change from the preF to postF state. Therefore, the structural changes in proteins must be regulated to produce a vaccine antigen that can efficiently induce antibodies with high virus-neutralizing activity. We successfully discovered several mutations that stabilized the antigen site Ø in the preF state, trimerized it, and improved the level of protein expression through observation and computational analysis of the RSV-F protein structure and amino acid mutation analysis of RSV strains. The four RSV-F protein mutants that resulted from the combination of these effective mutations stably conserved a wide range of preF- and trimeric preF-specific epitopes with high virus-neutralizing activity. Absorption assay using human serum revealed that mutants constructed bound to antibodies with virus-neutralizing activity that were induced by natural RSV infection, whereas they hardly bound to anti-postF antibodies without virus-neutralizing activity. Furthermore, mouse immunization demonstrated that our constructed mutants induced a high percentage of antibodies that bind to the preF-specific antigen site. These characteristics suggest that the mutants constructed can be superior vaccine antigens from the viewpoint of RSV infection prevention effect and safety. [ABSTRACT FROM AUTHOR]

This review article will summarize the vaccines and monoclonal antibodies currently under evaluation for the prevention of RSV disease in older infants, toddlers and young children. We will review the rationale for passive protection during the first months of life, and the role of active immunization afterwards, either with live attenuated, protein-based or mRNA vaccines. [ABSTRACT FROM AUTHOR]

The efforts to prevent respiratory syncytial virus (RSV) infection in infants span over half a century. RSV vaccine development began in the 1960s, and it confronted a significant disappointment after testing a formalin-inactivated RSV (FI RSV) vaccine candidate. This inactivated RSV vaccine was not protective. A large number of the vaccinated RSV-naive children, when subsequently exposed to natural RSV infection from wild-type virus in the community, developed severe lung inflammation termed enhanced respiratory disease. This resulted in a halt in RSV vaccine development. In the 1990s, attention turned to the potential for passive protection against severe RSV disease with immunoglobulin administration. This led to studies on using standard intravenous immunoglobulins in high-risk infants, followed by high-titer RSV immunoglobulin preparation and, subsequently, the development of RSV monoclonal antibodies. Over the past 25 years, palivizumab has been recognized as a safe and effective monoclonal antibody as a prevention strategy for RSV in high-risk children. Its high cost and need for monthly administration, however, has hindered its use to ~2% of the birth cohort, neglecting the vast majority of newborns, including healthy full-term infants who comprise the largest portion of RSV hospitalizations and the greatest part of the burden of RSV disease. Still these efforts, helped pave the way for the present advances in RSV prevention that hold promise for mitigating severe RSV disease for all infants. [ABSTRACT FROM AUTHOR]

Influenza remains a worldwide public health threat. Although seasonal influenza vaccines are currently the best means of preventing severe disease, the standard-of-care vaccines require frequent updating due to antigenic drift and can have low efficacy, particularly in vulnerable populations. Here, we demonstrate that a single administration of a recombinant adenovirus-associated virus (rAAV) vector expressing a computationally optimized broadly reactive antigen (COBRA)-derived influenza H1 hemagglutinin (HA) induces strongly neutralizing and broadly protective antibodies in naïve mice and ferrets with pre-existing influenza immunity. Following a lethal viral challenge, the rAAV-COBRA vaccine allowed for significantly reduced viral loads in the upper and lower respiratory tracts and complete protection from morbidity and mortality that lasted for at least 5 months post-vaccination. We observed no signs of antibody waning during this study. CpG motif enrichment of the antigen can act as an internal adjuvant to further enhance the immune responses to allow for lower vaccine dosages with the induction of unique interferon-producing CD4+ and CD8+ T cells specific to HA head and stem peptide sequences. Our studies highlight the utility of rAAV as an effective platform to improve seasonal influenza vaccines. IMPORTANCE Developing an improved seasonal influenza vaccine remains an ambitious goal of researchers and clinicians alike. With influenza routinely causing severe epidemics with the potential to rise to pandemic levels, it is critical to create an effective, broadly protective, and durable vaccine to improve public health worldwide. As a potential solution, we created a rAAV viral vector expressing a COBRA-optimized influenza hemagglutinin antigen with modestly enriched CpG motifs to evoke a robust and long-lasting immune response after a single intramuscular dose without needing boosts or adjuvants. Importantly, the rAAV vaccine boosted antibody breadth to future strains in ferrets with pre-existing influenza immunity. Together, our data support further investigation into the utility of viral vectors as a potential avenue to improve our seasonal influenza vaccines. [ABSTRACT FROM AUTHOR]

Measles is a highly transmissible systemic viral infection associated with substantial mortality primarily due to secondary infections. Measles induces lifelong immunity to reinfection but loss of immunity to other pathogens. An attenuated live virus vaccine is highly effective, but lapses in delivery have resulted in increasing cases worldwide. Although the primary cause of failure to control measles is failure to vaccinate, waning vaccine-induced immunity and the possible emergence of more virulent virus strains may also contribute. [ABSTRACT FROM AUTHOR]

Microcarrier-based cell culture systems have gained significant attention and popularity in tissue engineering and regenerative medicine. In this culture system, tissue cells are grown as a monolayer on the surface of small solid particles called microcarriers (100 to 300 μm), kept suspended in the culture medium by stirring. This technology has paved the way for creating engineered tissues, one of the cutting-edge topics in tissue engineering and regenerative medicine. Microcarrier-based approaches have been proposed for three-dimensional (3D) cell culture in which cellular morphology and functions are maintained in vivo. This paper provides an overview of the optimal characteristics such as microcarriers' size, shape, density and porosity. Various methods of preparation of microcarriers and surface modification techniques have been elaborated. Recent advances and applications of microcarriers in biotechnology fields, like the production of viral vaccines and recombinant proteins, culture and expansion of stem cells (SC), are described. [ABSTRACT FROM AUTHOR]

Enteroviruses are important human pathogens with diverse serotypes, posing a major challenge to develop vaccines for individual serotypes, the success of polio vaccines in controlling and eradicating polio, along with the recent emergence and high prevalence of enterovirus‐caused infectious diseases, highlights the importance of enterovirus vaccine development. Given our previous report on enteroviruses weakened by the 2 A S/T125A mutation, we assessed the potential of the EV‐A71 2A‐125A mutant as a vaccine candidate to address this challenge. We found that the 2A‐125A mutant caused transient mild symptoms, low viral loads, and no significant pathological changes mild pathological changes in hSCARB2‐KI mice, producing long‐lasting cross‐neutralizing antibodies against two EV‐A71 wild strains. Pre‐exposure to the 2A‐125A mutant substantially protected against the EV‐A71 Isehara wild‐type strain, causing minor pathologies, significantly reducing muscle and lung inflammation, and preventing neurological damage, with reduced viral loads in vivo. Pre‐exposure also distinctly suppressed the expression of pro‐inflammatory cytokines, correlating to the severity of clinical symptoms. Collectively, the EV‐A71 2A‐125A mutant was attenuated and could generate a robust and protective immune response, suggesting its potential as a vaccine candidate and global solution for specific enterovirus vaccine development. [ABSTRACT FROM AUTHOR]

Chlamydia trachomatis remains a major global health problem with increasing infection rates, requiring innovative vaccine solutions. Modified Vaccinia Virus Ankara (MVA) is a well-established, safe and highly immunogenic vaccine vector, making it a promising candidate for C. trachomatis vaccine development. In this study, we evaluated two novel MVA-based recombinant vaccines expressing spCTH522 and CTH522:B7 antigens. Our results show that while both vaccines induced CD4+ T-cell responses in C57BL/6J mice, they failed to generate antigen-specific systemic CD8+ T cells. Only the membrane-anchored CTH522 elicited strong IgG2b and IgG2c antibody responses. In an HLA transgenic mouse model, both recombinant MVAs induced Th1-directed CD4+ T cell and multifunctional CD8+ T cells, while only the CTH522:B7 vaccine generated antibody responses, underscoring the importance of antigen localization. Collectively, our data indicate that distinct antigen formulations can induce different immune responses depending on the mouse strain used. This research contributes to the development of effective vaccines by highlighting the importance of careful antigen design and the selection of appropriate animal models to study specific vaccine-induced immune responses. Future studies should investigate whether these immune responses provide protection in humans and should explore different routes of immunization, including mucosal and systemic immunization. [ABSTRACT FROM AUTHOR]

Background: Respiratory syncytial virus (RSV) is garnering increasing attention, with a growing number of subunit RSV vaccines under active clinical investigation. However, comprehensive evidence is limited. Methods: We conducted a comprehensive search across PubMed, Embase, the Cochrane Library, Web of Science, and ClinicalTrials.gov from database inception to 12 January 2024, focusing on published randomized controlled trials (RCTs). Results: A total of 17 studies were included, encompassing assessments of efficacy (5 studies), safety (17 studies), and immunogenicity (12 studies) of RSV subunit vaccines. The pooled risk ratio (RR) for RSV-associated acute respiratory infection (RSV-ARI) with subunit vaccines was 0.31 (95% CI: 0.23–0.43), for RSV-associated lower respiratory tract infection (RSV-LRTI), it was 0.32 (95% CI: 0.22–0.44), and for severe RSV-LRTI (RSV-SLRTI), it was 0.13 (95% CI: 0.06–0.29). There was no significant difference in serious adverse events (SAEs) between the vaccine and placebo groups, with a pooled RR of 1.05 (95% CI: 0.98–1.14). The pooled standardized mean difference (SMD) for the geometric mean titer (GMT) of neutralizing antibodies was 2.89 (95% CI: 2.43−3.35). Conclusion: Subunit RSV vaccines exhibit strong efficacy, favorable safety profiles, and robust immunogenicity. Future research should focus on the cost-effectiveness of various vaccines to enhance regional and national immunization strategies. [ABSTRACT FROM AUTHOR]

The first vaccine against chikungunya virus (CHIKV) was recently licensed in the U.S., Europe, and Canada (brand IXCHIQ®, referred to as VLA1553). Other pathogenic alphaviruses co-circulate with CHIKV and major questions remain regarding the potential of IXCHIQ to confer cross-protection for populations that are exposed to them. Here, we characterized the cross-neutralizing antibody (nAb) responses against heterotypic CHIKV and additional arthritogenic alphaviruses in individuals at one month, six months, and one year post-IXCHIQ vaccination. We characterized nAbs against CHIKV strains LR2006, 181/25, and a 2021 isolate from Tocantins, Brazil, as well as O'nyong-nyong virus (ONNV), Mayaro virus (MAYV), and Ross River virus (RRV). IXCHIQ elicited 100% seroconversion to each virus, with the exception of RRV at 83.3% seroconversion of vaccinees, and cross-neutralizing antibody potency decreased with increasing genetic distance from CHIKV. We compared vaccinee responses to cross-nAbs elicited by natural CHIKV infection in individuals living in the endemic setting of Puerto Rico at 8–9 years post-infection. These data suggest that IXCHIQ efficiently and potently elicits cross-nAb breadth that extends to related alphaviruses in a manner similar to natural CHIKV infection, which may have important implications for individuals that are susceptible to alphavirus co-circulation in regions of potential vaccine rollout. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) is an ancient global public health problem. Several strategies have been applied to develop new and more effective vaccines against TB, from attenuated or inactivated mycobacteria to recombinant subunit or genetic vaccines, including viral vectors. This review aimed to evaluate patents filed between 2010 and 2023 for TB vaccine candidates. It focuses on viral vector-based strategies. A search was carried out in Espacenet, using the descriptors "mycobacterium and tuberculosis" and the classification A61K39. Of the 411 patents preliminarily identified, the majority were related to subunit vaccines, with 10 patents based on viral vector platforms selected in this study. Most of the identified patents belong to the United States or China, with a concentration of patent filings between 2013 and 2023. Adenoviruses were the most explored viral vectors, and the most common immunodominant Mycobacterium tuberculosis (Mtb) antigens were present in all the selected patents. The majority of patents were tested in mouse models by intranasal or subcutaneous route of immunization. In the coming years, an increased use of this platform for prophylactic and/or therapeutic approaches for TB and other diseases is expected. Along with this, expanding knowledge about the safety of this technology is essential to advance its use. [ABSTRACT FROM AUTHOR]

Over the past few decades, dengue fever has emerged as a significant global health threat, affecting tropical and moderate climate regions. Current vaccines have practical limitations, there is a strong need for safer, more effective options. This study introduces novel vaccine candidates covering all four dengue virus (DENV) serotypes using virus-like particles (VLPs), a proven vaccine platform. The dengue virus envelope protein domain III (EDIII), the primary target of DENV-neutralizing antibodies, was either genetically fused or chemically coupled to bacteriophage-derived AP205-VLPs. To facilitate the incorporation of the large EDIII domain, AP205 monomers were dimerized, resulting in sterically optimized VLPs with 90 N- and C-termini. These vaccines induced high-affinity/avidity antibody titers in mice, and confirmed their protective potential by neutralizing different DENV serotypes in vitro. Administration of a tetravalent vaccine induced high neutralizing titers against all four serotypes without producing enhancing antibodies, at least not against DENV2. In conclusion, the vaccine candidates, especially when administered in a combined fashion, exhibit intriguing properties for potential use in the field, and exploring the possibility of conducting a preclinical challenge model to verify protection would be a logical next step. [ABSTRACT FROM AUTHOR]

mRNA vaccines are leading a medical revolution. mRNA technologies utilize the host's own cells as bio-factories to produce proteins that serve as antigens. This revolutionary approach circumvents the complicated processes involved in traditional vaccine production and empowers vaccines with the ability to respond to emerging or mutated infectious diseases rapidly. Additionally, the robust cellular immune response elicited by mRNA vaccines has shown significant promise in cancer treatment. However, the inherent instability of mRNA and the complexity of tumor immunity have limited its broader application. Although the emergence of pseudouridine and ionizable cationic lipid nanoparticles (LNPs) made the clinical application of mRNA possible, there remains substantial potential for further improvement of the immunogenicity of delivered antigens and preventive or therapeutic effects of mRNA technology. Here, we review the latest advancements in mRNA vaccines, including but not limited to target selection and delivery systems. This review offers a multifaceted perspective on this rapidly evolving field. [ABSTRACT FROM AUTHOR]

Numerous factors influence the magnitude and effector phenotype of vaccine-induced CD8+ T cells, thereby potentially impacting treatment efficacy. Here, we investigate the effect of vaccination dose, route of immunization, presence of a target antigen-expressing tumor, and heterologous prime-boost with peptide vaccine partner following vaccination with antigen-armed VSV-GP. Our results indicate that a higher vaccine dose increases antigen-specific CD8+ T cell proportions while altering the phenotype. The intravenous route induces the highest proportion of antigen-specific CD8+ T cells together with the lowest anti-viral response followed by the intraperitoneal, intramuscular, and subcutaneous routes. Moreover, the presence of a B16-OVA tumor serves as pre-prime, thereby increasing OVA-specific CD8+ T cells upon vaccination and thus altering the ratio of anti-tumor versus anti-viral CD8+ T cells. Interestingly, tumor-specific CD8+ T cells exhibit a different phenotype compared to bystander anti-viral CD8+ T cells. Finally, the heterologous combination of peptide and viral vaccine elicits the highest proportion of antigen-specific CD8+ T cells in the tumor and tumor-draining lymph nodes. In summary, we provide a basic immune characterization of various factors that affect anti-viral and vaccine target-specific CD8+ T cell proportions and phenotypes, thereby enhancing our vaccinology knowledge for future vaccine regimen designs. [ABSTRACT FROM AUTHOR]

Goat may represent a valid large animal model for human pathogens and new vaccines testing. Appropriate vaccine administration is a critical component of a successful immunization program. The wrong route of administration may reduce the efficacy of the vaccine, whereas the proper administration strategy can enhance it. Viral vectors have been employed successfully for goat and sheep immunization; however, no data concerning the vaginal route are available. A viral vector's ability to transduce the site of inoculation is of primary interest. In this study, a fast and reliable ex vivo assay for testing the transduction capability of an Ad5-based vector when intravaginally administered was developed. An Ad5 vector delivering an expression cassette with a bicistronic reporter gene, Ad5-CMV-turboGFP-IRES-Luc2, was constructed. We demonstrated Ad5-CMV-turboGFP-IRES-Luc2's ability to transduce caprine vaginal mucosa by ex vivo bioluminescent imaging (BLI) employing a simple CCD camera apparatus for chemiluminescence western immunoblotting. These data, though simple, provide valuable insights into developing a vaginal immunization strategy using a viral vector-based vaccine to protect against pathogens causing genital diseases. [ABSTRACT FROM AUTHOR]

The introduction of a new vaccine into immunization programs represents a significant advancement in the global effort to combat vaccine-preventable diseases. Data from the World Health Organization support that immunization prevents between 2 and 3 million deaths each year across various diseases, underscoring its pivotal role in global health. The present study aims to assess the knowledge, attitudes, and anticipated vaccination practices among health professionals in Central Greece in response to the potential introduction of new Respiratory Syncytial Virus (RSV) vaccination guidelines by the National Vaccines Committee. Among the 450 health professionals solicited for the study, 219 provided responses, yielding a response rate of approximately 55%. A substantial majority (70.3%) accurately identified the vaccine's current availability, and 62.1% were aware of the current recommendation for RSV vaccination in pregnant women. In response to whether health professionals support the inclusion of an RSV vaccine in the national vaccination program if it becomes commercially available and is recommended by the Greek National Immunization Program, general practitioners showed the most support, with an average score of 4.86 (95% CI, 4.69–5.00), followed by pediatricians at 4.76 (95% CI, 4.63–4.89), pulmonologists at 4.68 (95% CI, 4.36–5.00), and obstetricians at 4.33 (95% CI, 3.95–4.71). Concerning general opinions on vaccinations, a high level of agreement was noted among the majority of health professionals, excluding nurses. Pharmacists recorded the highest agreement, with a perfect score of 5 (CI, 5.00–5.00), followed closely by pediatricians at 4.99 (CI, 4.97–5.00), GPs at 4.95 (CI, 4.85–5.00), pulmonologists at 4.93 (CI, 4.83–5.00), obstetricians at 4.74 (CI, 4.42–5.00), and nurses at 3.80 (CI, 3.06–4.54). A tailored approach to education is needed to ensure that healthcare professionals can communicate more effectively about RSV risks and vaccination benefits, fostering a proactive stance towards disease prevention and patient care. In essence, our study underscores the importance of knowledge in shaping a compassionate and responsive healthcare environment, ready to meet the challenges of RSV head-on. [ABSTRACT FROM AUTHOR]

Enhancing livestock biosecurity is critical to safeguard the livelihoods of farmers, global and local economies, and food security. Vaccination is fundamental to the control and prevention of exotic and endemic high-priority infectious livestock diseases. Successful implementation of vaccination in a biosecurity plan is underpinned by a strong understanding of correlates of protection--those elements of the immune response that can reliably predict the level of protection from viral challenge. While correlates of protection have been successfully characterized for many human viral vaccines, for many highpriority livestock viral diseases, including African swine fever and foot and mouth disease, they remain largely uncharacterized. Current literature provides insights into potential correlates of protection that should be assessed during vaccine development for these high-priority mammalian livestock viral diseases. Establishment of correlates of protection for biosecurity purposes enables immune surveillance, rationale for vaccine development, and successful implementation of livestock vaccines as part of a biosecurity strategy. [ABSTRACT FROM AUTHOR]