Vaccine Development Research Articles

Review of the current TB human infection studies for use in accelerating TB vaccine development: A meeting report.

Tools to evaluate and accelerate tuberculosis (TB) vaccine development are needed to advance global TB control strategies. Validated human infection studies for TB have the potential to facilitate breakthroughs in understanding disease pathogenesis, identify correlates of protection, develop diagnostic tools, and accelerate and de-risk vaccine and drug development. However, key challenges remain for realizing the clinical utility of these models, which require further discussion and alignment amongst key stakeholders. In March 2023, the Wellcome Trust and the International AIDS Vaccine Initiative (IAVI) convened international experts involved in developing both TB and Bacillus Calmette-Guerin (BCG) human infection studies (including mucosal and intradermal challenge routes) to discuss the status of each of the models and the key enablers to move the field forward. This report provides a summary of the presentations and discussion from the meeting. Discussions identified key issues, including demonstrating model validity, to provide confidence for vaccine developers, which may be addressed through demonstration of known vaccine effects, e.g. BCG vaccination in specific populations, and by comparing results from field efficacy and human infection studies. The workshop underscored the importance of establishing safe and acceptable studies in high-burden settings, and the need to validate more than one model to allow for different scientific questions to be addressed as well as to provide confidence to vaccine developers and regulators around use of human infection study data in vaccine development and licensure pathways.

Vaccine process technology-Adecade of progress.

In the past decade, new approaches to the discovery and development of vaccines have transformed the field. Advances during the COVID-19 pandemic allowed the production of billions of vaccine doses per year using novel platforms such as messenger RNA and viral vectors. Improvements in the analytical toolbox, equipment, and bioprocess technology have made it possible to achieve both unprecedented speed in vaccine development and scale of vaccine manufacturing. Macromolecular structure-function characterization technologies, combined with improved modeling and data analysis, enable quantitative evaluation of vaccine formulations at single-particle resolution and guided design of vaccine drug substances and drug products. These advances play a major role in precise assessment of critical quality attributes of vaccines delivered by newer platforms. Innovations in label-free and immunoassay technologies aid in the characterization of antigenic sites and the development of robust in vitro potency assays. These methods, along with molecular techniques such as next-generation sequencing, will accelerate characterization and release of vaccines delivered by all platforms. Process analytical technologies for real-time monitoring and optimization of process steps enable the implementation of quality-by-design principles and faster release of vaccine products. In the next decade, the field of vaccine discovery and development will continue to advance, bringing together new technologies, methods, and platforms to improve human health.

Rapid development and mass production of SARS-CoV-2 neutralizing chicken egg yolk antibodies with protective efficacy in hamsters

Despite the record speed of developing vaccines and therapeutics against the SARS-CoV-2 virus, it is not a given that such success can be secured in future pandemics. In addition, COVID-19 vaccination and application of therapeutics remain low in developing countries. Rapid and low cost mass production of antiviral IgY antibodies could be an attractive alternative or complementary option for vaccine and therapeutic development. In this article, we rapidly produced SARS-CoV-2 antigens, immunized hens and purified IgY antibodies in 2 months after the SARS-CoV-2 gene sequence became public. We further demonstrated that the IgY antibodies competitively block RBD binding to ACE2, neutralize authentic SARS-CoV-2 virus and effectively protect hamsters from SARS-CoV-2 challenge by preventing weight loss and lung pathology, representing the first comprehensive study with IgY antibodies. The process of mass production can be easily implemented in most developing countries and hence could become a new vital option in our toolbox for combating viral pandemics. This study could stimulate further studies, optimization and potential applications of IgY antibodies as therapeutics and prophylactics for human and animals.

Enhancing tuberculosis vaccine development: a deconvolution neural network approach for multi-epitope prediction

Tuberculosis (TB) a disease caused by Mycobacterium tuberculosis (Mtb) poses a significant threat to human life, and current BCG vaccinations only provide sporadic protection, therefore there is a need for developing efficient vaccines. Numerous immunoinformatic methods have been utilized previously, here for the first time a deep learning framework based on Deconvolutional Neural Networks (DCNN) and Bidirectional Long Short-Term Memory (DCNN-BiLSTM) was used to predict Mtb Multiepitope vaccine (MtbMEV) subunits against six Mtb H37Rv proteins. The trained model was used to design MEV within a few minutes against TB better than other machine learning models with 99.5% accuracy. The MEV has good antigenicity, and physiochemical properties, and is thermostable, soluble, and hydrophilic. The vaccine's BLAST search ruled out the possibility of autoimmune reactions. The secondary structure analysis revealed 87% coil, 10% beta, and 2% alpha helix, while the tertiary structure was highly upgraded after refinement. Molecular docking with TLR3 and TLR4 receptors showed good binding, indicating high immune reactions. Immune response simulation confirmed the generation of innate and adaptive responses. In-silico cloning revealed the vaccine is highly expressed in E. coli. The results can be further experimentally verified using various analyses to establish a candidate vaccine for future clinical trials.

Current Strategies for Vaccine Prophylaxis of Lyme Disease

Relevance. Lyme disease (LD) remains an important public health problem, especially in Russia, where the incidence is consistently high. To date, there is still no available vaccine against LD, and prevention involves non-specific measures. Aim: to review the literature and summarise data on progress, approaches and strategies for LD vaccine development. Conclusions. The first LD vaccines were developed in the 1990s. An OspA-based vaccine (LYMErix) was commercially available in the early 2000s but not widely distributed. An important milestone in the development of LD vaccines was the shift from the development of monovalent vaccines based on a single type of outer surface protein to the development of multivalent combinations that provide protection against different Borrelia genospecies. A multivalent OspA-based vaccine (VLA15) is in phase III clinical trials and is likely to be the next LD vaccine available on the market. New genetic strategies for vaccine development, identification of new immunogens, and development of vaccines targeting different parts of the LD transmission cycle are of broad interest for further development of LD vaccines.

National Concept of Development of Vaccine Prophylaxis in Russia

The article is dedicated to outlining the conceptual directions for the development of vaccination in the Russian Federation. The provisions of the concept are formulated based on the authors' years of research on vaccination issues and analysis of data from domestic and foreign scientific literature. The main provisions of the concept aim at strengthening the state policy in the field of vaccination, reconstructing and expanding enterprises for the production of domestic vaccines, developing and improving immunobiological medicinal products against current infections, refining the National Immunization Schedule and Vaccination Schedule according to epidemiological indications; further promoting the WHO's "lifelong immunization" strategy; developing regional immunization programs; implementing a risk-oriented approach in the development of immunization programs; developing a system for monitoring post-vaccination complications; implementing epidemiological surveillance of vaccination as a methodology for assessing the strategy and tactics of immunization in accordance with the epidemiological situation; ensuring commitment to vaccination among the population, healthcare workers, and legislative and executive authorities.

Immune Responses to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Vaccines: Updated Insights

Background: Using a multidisciplinary approach, this review explores and investigates the relationship between immune responses, effectiveness, and results of various vaccination strategies among a range of demographics. Moreover, this review aims to aid healthcare professionals in understanding the intricacies of immune responses and their implications for future vaccine development.Methodology: In this systematic review, we employed an electronic online database platform including the National Centre for Biotechnology Information (NCBI), the National Institute for Health and Clinical Excellence (NICE), and the World Health Organization (WHO) for evidence-based material, utilizing the keywords throughout this literature review.Results: This review provides a detailed framework regarding immune responses to the COVID- 19 vaccine, based on demographics, age, sex, types of immunity, and immunization strategies. Such research can provide important academic support for the development of not only COVID- 19 vaccines but also other vaccines.Conclusions: Overall, immune responses tended to dwindle a few months after vaccine administration. This is because B cells block SARS-CoV-2 from infecting cells via antibodies and T cells destroy infected cells. The most efficient tool for providing long-lasting protection against SARS-CoV-2 is vaccination. Humans have developed immunity to SARS-CoV-2, particularly antibody-mediated humoral immunity. The development of vaccines across the whole family of coronaviruses that target antibody epitopes (antigenic determinants) prevents the emergence of mutant strains.

Intranasal influenza-vectored COVID-19 vaccines confer broad protection against SARS-CoV-2 XBB variants in hamsters

Abstract The XBB.1.5 subvariant has garnered significant attention due to its exceptional immune evasion and transmissibility. Significantly, the evolutionary trajectory of SARS-CoV-2 has shown continual progression, with a recent global shift observed from XBB to BA.2.86, exemplified by the emergence of the predominant JN.1 subvariant. This phenomenon highlights the need for vaccines that can provide broad-spectrum antigenic coverage. In this study, we utilized a NS1-deleted (dNS1) influenza viral vector to engineer an updated live attenuated vectored vaccine called dNS1-XBB-RBD. This vaccine encodes the receptor binding domain (RBD) protein of the XBB.1.5 strain. Our findings demonstrate that the dNS1-XBB-RBD vaccine elicits a similar systemic and mucosal immune response compared to its prototypic form, dNS1-RBD. In hamsters, the dNS1-XBB-RBD vaccine provided robust protection against the SARS-CoV-2 immune-evasive strains XBB.1.9.2.1 and Beta. Remarkably, nasal vaccination with dNS1-RBD, which encodes the ancestor RBD gene, also effectively protected hamsters against both the XBB.1.9.2.1 and Beta strains. These results provide valuable insights about nasal influenza-vectored vaccine and present a promising strategy for the development of a broad-spectrum vaccine against COVID-19 in the future.

The step-by-step assembly mechanism of secreted flavivirus NS1 tetramer and hexamer captured at atomic resolution.

Flaviviruses encode a conserved, membrane-associated nonstructural protein 1 (NS1) with replication and immune evasion functions. The current knowledge of secreted NS1 (sNS1) oligomers is based on several low-resolution structures, thus hindering the development of drugs and vaccines against flaviviruses. Here, we revealed that recombinant sNS1 from flaviviruses exists in a dynamic equilibrium of dimer-tetramer-hexamer states. Two DENV4 hexameric NS1 structures and several tetrameric NS1 structures from multiple flaviviruses were solved at atomic resolution by cryo-EM. The stacking of the tetrameric NS1 and hexameric NS1 is facilitated by the hydrophobic β-roll and connector domains. Additionally, a triacylglycerol molecule located within the central cavity may play a role in stabilizing the hexamer. Based on differentiated interactions between the dimeric NS1, two distinct hexamer models (head-to-head and side-to-side hexamer) and the step-by-step assembly mechanisms of NS1 dimer into hexamer were proposed. We believe that our study sheds light on the understanding of the NS1 oligomerization and contributes to NS1-based therapies.

Development and evaluation of inactivated vaccines incorporating a novel Senecavirus A strain-based Immunogen and various adjuvants in mice

Porcine idiopathic vesicular disease (PIVD), one of several clinically indistinguishable vesicular diseases of pigs, is caused by the emerging pathogen Senecavirus A (SVA). Despite the widespread prevalence of porcine SVA infection, no effective commercial vaccines for PIVD prevention and control are available, due to high costs associated with vaccine testing in pigs, considerable SVA diversity, and SVA rapid evolution. In this study, SVA CH/JL/2022 (OP562896), a novel mutant SVA strain derived from an isolate obtained from a pig farm in Jilin Province, China, was inactivated then combined with four adjuvants, MONTANIDETM GEL02 PR (GEL 02), MONTANIDETM ISA 201 VG (ISA 201), MONTANIDETM IMG 1313 VG N (IMS1313), or Rehydragel LV (LV). The resulting inactivated SVA CH/JL/2022 vaccines were assessed for efficacy in mice and found to induce robust in vivo lymphocyte proliferation responses and strong IgG1, IgG2a, and neutralizing antibody responses with IgG2a/IgG1 ratios of <1. Furthermore, all vaccinated groups exhibited significantly higher levels of serum cytokines IL-2, IL-4, IL-6, and IFN as compared to unvaccinated mice. These results indicate that all vaccines elicited both Th1 and Th2 responses, with Th2 responses predominating. Moreover, vaccinated mice exhibited enhanced resistance to SVA infection, as evidenced by reduced viral RNA levels and SVA infection-induced histopathological changes. Collectively, our results demonstrate that the SVA-GEL vaccine induced more robust immunological responses in mice than did the other three vaccines, thus highlighting the potential of SVA-GEL to serve an effective tool for preventing and controlling SVA infection.

Development of novel Streptococcus equi vaccines with an assessment of their immunizing potentials and protective efficacies

Strangles is a highly contagious disease of the equine upper respiratory tract caused by Streptococcus equi subspecies. Streptococcus equi subsp. equi (S. equi) and Streptococcus equi subsp. zooepidemicus (S. zooepidemicus) was isolated, as local, hot, and field strains, from horses clinically suffering from respiratory distress. The isolated Streptococci were identified using bacteriological and molecular techniques. Four formulations of inactivated S. equi vaccines were developed and evaluated. The first formulation was prepared using the S. equi isolates, adjuvanted with MONTANIDE GEL adjuvant, while the second formulation was adjuvanted with MONTANIDE ISA-70 adjuvant. The other 2 formulations were inactivated combined vaccines prepared from both S. equi and S. zooepidemicus isolates. The 3rd formulation was the combined isolates adjuvanted with MONTANIDE GEL while the 4th formulation was the combined isolates adjuvanted with MONTANIDE ISA-70. The developed vaccines’ physical properties, purity, sterility, safety, and potency were ensured. The immunizing efficacy was determined in isogenic BALB/c mice and white New Zealand rabbits using the passive hemagglutination test. Also, the antibodies’ titer of the combined S. equi and S. zooepidemicus vaccine adjuvanted with MONTANIDE ISA-70 in foals was tracked using an indirect enzyme-linked immunosorbent assay. The protective efficacy of the developed vaccines was determined using a challenge test in both laboratory and field animal models, where a 75% protection rate was achieved. The combined vaccine proved to be more efficacious than the monovalent vaccine. Also, the MONTANIDE ISA-70 adjuvant provided significant protective efficacy than the MONTANIDE GEL. The current work is introducing a very promising mitigative and strategic controlling solution for strangles.

Update on feline calicivirus: viral evolution, pathogenesis, epidemiology, prevention and control

Feline calicivirus (FCV) is a prevalent and impactful viral pathogen affecting domestic cats. As an RNA virus, FCV exhibits high mutability and genetic plasticity, enabling its persistence within cat populations. Viral genetic diversity is associated with a broad spectrum of clinical manifestations, ranging from asymptomatic infections and mild oral and upper respiratory tract diseases to the potential development of virulent systemic, and even fatal conditions. This diversity poses distinctive challenges in diagnosis, treatment, and prevention of diseases caused by FCV. Over the past four decades, research has significantly deepened understanding of this pathogen, with an emphasis on molecular biology, evolutionary dynamics, vaccine development, and disease management strategies. This review discusses various facets of FCV, including its genomic structure, evolution, innate immunity, pathogenesis, epidemiology, and approaches to disease management. FCV remains a complex and evolving concern in feline health, requiring continuous research to enhance understanding of its genetic diversity, to improve vaccine efficacy, and to explore novel treatment options.

Respiratory syncytial virus vaccination during pregnancy for improving infant outcomes.

Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infections (LRTIs) in infants. Maternal RSV vaccination is a preventive strategy of great interest, as it could have a substantial impact on infant RSV disease burden. In recent years, the clinical development of maternal RSV vaccines has advanced rapidly. To assess the efficacy and safety of maternal respiratory syncytial virus (RSV) vaccination for preventing RSV disease in infants. We searched Cochrane Pregnancy and Childbirth's Trials Register and two other trials registries on 21 October 2022. We updated the search on 27 July 2023, when we searched MEDLINE, Embase, CENTRAL, CINAHL, and two trials registries. Additionally, we searched the reference lists of retrieved studies and conference proceedings. There were no language restrictions on our searches. We included randomised controlled trials (RCTs) comparing maternal RSV vaccination with placebo or no intervention in pregnant women of any age. The primary outcomes were hospitalisation with clinically confirmed or laboratory-confirmed RSV disease in infants. The secondary outcomes covered adverse pregnancy outcomes (intrauterine growth restriction, stillbirth, and maternal death) and adverse infant outcomes (preterm birth, congenital abnormalities, and infant death). We used standard Cochrane methods and assessed the certainty of evidence using the GRADE approach. We included six RCTs (25 study reports) involving 17,991 pregnant women. The intervention was an RSV pre-F protein vaccine in four studies, and an RSV F protein nanoparticle vaccine in two studies. In all studies, the comparator was a placebo (saline, formulation buffer, or sterile water). We judged four studies at overall low risk of bias and two studies at overall high risk (mainly due to selection bias). All studies were funded by pharmaceutical companies. Maternal RSV vaccination compared with placebo reduces infant hospitalisation with laboratory-confirmed RSV disease (risk ratio (RR) 0.50, 95% confidence interval (CI) 0.31 to 0.82; 4 RCTs, 12,216 infants; high-certainty evidence). Based on an absolute risk with placebo of 22 hospitalisations per 1000 infants, our results represent 11 fewer hospitalisations per 1000 infants from vaccinated pregnant women (15 fewer to 4 fewer). No studies reported infant hospitalisation with clinically confirmed RSV disease. Maternal RSV vaccination compared with placebo has little or no effect on the risk of congenital abnormalities (RR 0.96, 95% CI 0.88 to 1.04; 140 per 1000 with placebo, 5 fewer per 1000 with RSV vaccination (17 fewer to 6 more); 4 RCTs, 12,304 infants; high-certainty evidence). Maternal RSV vaccination likely has little or no effect on the risk of intrauterine growth restriction (RR 1.32, 95% CI 0.75 to 2.33; 3 per 1000 with placebo, 1 more per 1000 with RSV vaccination (1 fewer to 4 more); 4 RCTs, 12,545 pregnant women; moderate-certainty evidence). Maternal RSV vaccination may have little or no effect on the risk of stillbirth (RR 0.81, 95% CI 0.38 to 1.72; 3 per 1000 with placebo, no difference with RSV vaccination (2 fewer to 3 more); 5 RCTs, 12,652 pregnant women). There may be a safety signal warranting further investigation related to preterm birth. This outcome may be more likely with maternal RSV vaccination, although the 95% CI includes no effect, and the evidence is very uncertain (RR 1.16, 95% CI 0.99 to 1.36; 6 RCTs, 17,560 infants; very low-certainty evidence). Based on an absolute risk of 51 preterm births per 1000 infants from pregnant women who received placebo, there may be 8 more per 1000 infants from pregnant women with RSV vaccination (1 fewer to 18 more). There was one maternal death in the RSV vaccination group and none in the placebo group. Our meta-analysis suggests that RSV vaccination compared with placebo may have little or no effect on the risk of maternal death (RR 3.00, 95% CI 0.12 to 73.50; 3 RCTs, 7977 pregnant women; low-certainty evidence). The effect of maternal RSV vaccination on the risk of infant death is very uncertain (RR 0.81, 95% CI 0.36 to 1.81; 6 RCTs, 17,589 infants; very low-certainty evidence). The findings of this review suggest that maternal RSV vaccination reduces laboratory-confirmed RSV hospitalisations in infants. There are no safety concerns about intrauterine growth restriction and congenital abnormalities. We must be careful in drawing conclusions about other safety outcomes owing to the low and very low certainty of the evidence. The evidence available to date suggests RSV vaccination may have little or no effect on stillbirth, maternal death, and infant death (although the evidence for infant death is very uncertain). However, there may be a safety signal warranting further investigation related to preterm birth. This is driven by data from one trial, which is not fully published yet. The evidence base would be much improved by more RCTs with substantial sample sizes and well-designed observational studies with long-term follow-up for assessment of safety outcomes. Future studies should aim to use standard outcome measures, collect data on concomitant vaccines, and stratify data by timing of vaccination, gestational age at birth, race, and geographical setting.

Abstract PO4-16-05: Identification of functional HLA-A*11:01-restricted driver gene PIK3CA mutation specific T-cell receptors

Abstract The adoptive transfer of genetically engineered T-cell receptors (TCR-T) has emerged as a promising therapeutic strategy for the treatment of solid tumors. Recent clinical trials have demonstrated the safety and efficacy of TCR-T cell therapies against certain types of metastatic solid cancers. In our study, we aimed to investigate the potential of TCR-T cell therapies targeting neoantigens, which are exclusively expressed in cancer cells, with a focus on metastatic breast cancer (MBC). Specifically, we identified four driver missense mutations (PIK3CA E542K, E545K, H1047L, and H1047R) frequently observed in MBC patients and utilized computational tools to predict the generation of neoantigens. Utilizing NetMHCpan V.4.1, we performed screening of peptides spanning the mutation region and predicted a neoantigen epitope, PIK3CA_H1047L, to bind with HLA-A*11:01. To validate the presentation and stability of the neoantigen epitope, we employed TAP1-deficient K562 cells and observed stable expression of the mutant peptide-major histocompatibility complex (MHC) complex on the cell membrane. Subsequently, we isolated T cells from healthy donors possessing the HLA-A11:01 genotype, and subjected them to successive stimulations with neopeptide-pulsed dendritic cells. T cells stimulated with neopeptide were examined for neoantigen specificity using an IFN-γ ELISpot assay. Employing pMHC tetramer staining and single-cell sorting via flow cytometry, we successfully isolated five HLA-A11:01-restricted PIK3CA_H1047L-specific TCRs. Through lentivirus transduction of these TCRs into T cells, we achieved the generation of TCR-T cells that exhibited potent and specific activity exclusively against the PIK3CA_H1047L neoantigen. The functionality of the TCR-T cells was confirmed through assessments of CD137 expression, IFN-γ secretion, and cytotoxicity assays. In conclusion, our study demonstrates T cell responses towards neoantigens derived from PIK3CA, a commonly observed driver mutation in MBC. Furthermore, we successfully isolated five distinct neoantigen-specific TCRs that specifically recognized the PIK3CA_H1047L mutation and were restricted to the prevalent HLA-A*11:01 allele. The transfer of these TCRs into T cells resulted in the generation of TCR-T products exhibiting remarkable activity against the PIK3CA_H1047L neoantigen. These findings strongly encourage further investigation into TCRs targeting driver mutations in MBC, with the aim of advancing neoantigen-targeted TCR-T therapies into clinical trials. Additionally, the PIK3CA_H1047L neoantigen holds great promise as a potential candidate for the development of effective cancer vaccines. Citation Format: Meiying Shen, Xiaojian Han, Siyin Chen, Aishun Jin, Shengchun Liu. Identification of functional HLA-A*11:01-restricted driver gene PIK3CA mutation specific T-cell receptors [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-16-05.

Leveraging Decentralized Clinical Trial Management Systems (dCTMS) to Advance Science: Exploring Challenges related to the Diffusion of Innovation and its Execution

Decentralized clinical trials (DCTs) recently gained attention in research necessary for drug development. While the COVID-19 pandemic proved to be a challenging time in this arena, drug development was a critical area of emphasis in the rapid development of vaccines. DCTs were necessary to allow research activities to occur across many locations. Although the use of DCTs play a pivotal role in reshaping healthcare, as technology expands further into the digital space implementation challenges must be considered. A working group of experts assembled, during an interactive learning exercise at the Conv2X conference (2023), to explore challenges related to the diffusion of innovation among key stakeholders. Common “pain points” of technology and an innovative approach that used a blockchain anchored solution were presented. Experts were divided into three stakeholder groups (patients, payers, and pharmaceutical sponsor) which reconvened for an overall discussion. Several themes, that can be supported by blockchain technology, emerged. These include enhanced efficiencies, patient experience / demographic diversity, data integrity / privacy / security, and cost-effectiveness. Future research may focus on additional stakeholder groups that are less familiar with these technological advances and using technology to increase diversity in study populations.

Exploring the Communication, Information, and Education Strategies of the Indonesian FDA for COVID-19 Vaccine Development

The COVID-19 pandemic has become a complicated problem faced by the world. The absence of specific antiviral drugs or vaccines at the beginning of the outbreak made the public health approach the primary strategy for preventing the spread of COVID-19. The lack of transparency at the start of the COVID-19 outbreak also led to public misinformation. WHO called it an infodemic, an excess of information, whether true or not, making it difficult for people to determine valid references. In Indonesia, misinformation on health matters is not a new difficulty and is in the top rank along with socio-political. The government utilizes social media to provide information to the citizens. Social media itself has a vital role in the infodemic as a medium for disseminating information, whether credible or not. The Indonesian FDA plays an essential role in conducting education through social media. This study aims to map the elements forming citizens' engagement in Indonesian FDA social media use, especially in disseminating information about the COVID-19 vaccine. This study uses a regression method with citizens' engagement (calculated from the number of likes and comments) as the dependent variable. Three independent variables form citizen engagement elements: media richness, content production, and content type defined by the government. The sentiment toward government Instagram posts was measured by analyzing citizens' comments using the dataset from InSet Semantic Lexicon. Based on negative binomial regression results, data obtained that the framework developed in this research was statistically significant in observing the phenomenon. Media richness and content production significantly affect citizens' engagement. On the other hand, original and informative content encourages more citizen engagement. Generally, public sentiment on Indonesian FDA Instagram content, both head office and regional offices, tends to be more positive than negative.

Opportunities and challenges for T cell-based influenza vaccines.

Vaccination remains our main defence against influenza, which causes substantial annual mortality and poses a serious pandemic threat. Influenza virus evades immunity by rapidly changing its surface antigens but, even when the vaccine is well matched to the current circulating virus strains, influenza vaccines are not as effective as many other vaccines. Influenza vaccine development has traditionally focused on the induction of protective antibodies, but there is mounting evidence that T cell responses are also protective against influenza. Thus, future vaccines designed to promote both broad T cell effector functions and antibodies may provide enhanced protection. As we discuss, such vaccines present several challenges that require new strategic and economic considerations. Vaccine-induced T cells relevant to protection may reside in the lungs or lymphoid tissues, requiring more invasive assays to assess the immunogenicity of vaccine candidates. T cell functions may contain and resolve infection rather than completely prevent infection and early illness, requiring vaccine effectiveness to be assessed based on the prevention of severe disease and death rather than symptomatic infection. It can be complex and costly to measure T cell responses and infrequent clinical outcomes, and thus innovations in clinical trial design are needed for economic reasons. Nevertheless, the goal of more effective influenza vaccines justifies renewed and intensive efforts.

Pharmacokinetic and Environmental Risk Assessment of Prime-2-CoV, a Non-Replicating Orf Virus-Based Vaccine against SARS-CoV-2

Viral vector vaccines represent a substantial advancement in immunization technology, offering numerous benefits over traditional vaccine modalities. The Orf virus (ORFV) strain D1701-VrV is a particularly promising candidate for vaccine development due to its distinctive attributes, such as a good safety profile, the ability to elicit both humoral and cellular immunity, and its favorable genetic and thermal stability. Despite ORFV’s theoretical safety advantages, such as its narrow host range and limited systemic spread post-inoculation, a critical gap persists between these theoretical benefits and the empirical evidence regarding its in vivo safety profile. This discrepancy underscores the need for comprehensive preclinical validations to bridge this knowledge gap, especially considering ORFV’s use in humans. Our research introduces Prime-2-CoV, an innovative ORFV-based vaccine candidate against COVID-19, designed to elicit a robust immune response by expressing SARS-CoV-2 Nucleocapsid and Spike proteins. Currently under clinical trials, Prime-2-CoV marks the inaugural application of ORFV in human subjects. Addressing the aforementioned safety concerns, our extensive preclinical evaluation, including an environmental risk assessment (ERA) and detailed pharmacokinetic studies in rats and immunocompromised NOG mice, demonstrates Prime-2-CoV’s favorable pharmacokinetic profile, negligible environmental impact, and minimal ERA risks. These findings not only affirm the vaccine’s safety and efficacy but also pioneer the use of ORFV-based therapeutics, highlighting its potential for wider therapeutic applications.

Development of Vaccine Candidates Against Mycobacterium Tuberculosis in 2019-2023

ABSTRACT With extensive use of the Bacillus Calmette–Guérin (BCG) vaccine, the global prevalence of Mycobacterium tuberculosis (MTB) remains. A number of vaccines proposed to cure and prevent tuberculosis (TB) infection are undergoing various stages of clinical trials. Although vaccine production is progressing, more attention is needed. A number of TB vaccines are currently undergoing clinical trials, most of which rely on a combination of proteins and/or adjuvants or recombinant viral vectors specific for MTB antigens. We tried to cover the range of TB vaccines in this study by analyzing their composition, the immunological responses they elicit, and the stages of clinical trials. To find out the Development Of Prospective Vaccines Against Mycobacterium Tuberculosis. This research uses a literature review, between August 2023 and November 2023, the authors of this literature review checked PubMed, Science Direct, Google Scholar, and other databases containing research findings or scientific articles. Only studies that met the above search criteria were included in the systematic review. Many recently developed tuberculosis vaccines are reportedly in the final stages of clinical trials, where they have significantly strengthened the immune system and even produced protection against the host. Immunization produced by vaccines that have successfully passed the initial stages of clinical trials is safe and effective, and can even surpass BCG in terms of immunity.  Based on the description above, it can be concluded that many recently developed tuberculosis vaccines are reported to be in the final stages of clinical trials, where they have significantly strengthened the immune system and even produced protection against the host. Immunization produced by vaccines that have successfully passed the initial stages of clinical trials is safe and effective, and can even surpass BCG in terms of immunity. With the development of new TB vaccines that strengthen the body's immunity and create effective delivery mechanisms, hopes for TB treatment and prevention are increasing. The development of vaccine effects can be facilitated, in part, through the use of effective delivery mechanisms, which have also been used in TB vaccines. Keywords: Tuberculosis, Vaccine, Bacteria, Mycobacterium Tuberculosis, BCG

Evaluation of the precision of the Plasmodium knowlesi growth inhibition assay for Plasmodium vivax Duffy-binding protein-based malaria vaccine development

Recent data indicate increasing disease burden and importance of Plasmodium vivax (Pv) malaria. A robust assay will be essential for blood-stage Pv vaccine development. Results of the in vitro growth inhibition assay (GIA) with transgenic P. knowlesi (Pk) parasites expressing the Pv Duffy-binding protein region II (PvDBPII) correlate with in vivo protection in the first PvDBPII controlled human malaria infection (CHMI) trials, making the PkGIA an ideal selection tool once the precision of the assay is defined. To determine the precision in percentage of inhibition in GIA (%GIA) and in GIA50 (antibody concentration that gave 50 %GIA), ten GIAs with transgenic Pk parasites were conducted with four different anti-PvDBPII human monoclonal antibodies (mAbs) at concentrations of 0.016 to 2mg/mL, and three GIAs with eighty anti-PvDBPII human polyclonal antibodies (pAbs) at 10 mg/mL. A significant assay-to-assay variation was observed, and the analysis revealed a standard deviation (SD) of 13.1 in the mAb and 5.94 in the pAb dataset for %GIA, with a LogGIA50 SD of 0.299 (for mAbs). Moreover, the ninety-five percent confidence interval (95 %CI) for %GIA or GIA50 in repeat assays was calculated in this investigation. The error range determined in this study will help researchers to compare PkGIA results from different assays and studies appropriately, thus supporting the development of future blood-stage malaria vaccine candidates, specifically second-generation PvDBPII-based formulations.