Search Results (2,657)

A novel flow process to produce low-molecular-weight (Mwt) methacrylate oligomer mixtures that have potential as vaccine adjuvants and chain transfer agents (CTAs) is reported. The chemistry and process were designed to significantly reduce the number of stages required to manufacture methyl methacrylate oligomer-in-monomer mixtures with an oligomer Mwt range of dimers to pentamers and >50% conversion. Combining rapid in-flow, in situ catalytic chain transfer polymerization catalyst synthesis and volumetric microwave heating of the reaction medium resulted in catalyst flow synthesis being completed in <4 min, removing the need to pre-synthesize it. The steady-state operation was then successfully maintained with very low levels of external energy, as the process utilized the reaction exotherm. The microwave process outperformed a comparative conventionally heated system by delivering a 20% increase in process throughput with no change in final product quality or conversion. Additionally, combining flow and in situ catalyst processing enabled the use of a more oxidatively unstable catalyst. This allowed for in situ catalyst deactivation post-generation of the oligomers, such that residual catalyst did not need to be removed prior to preparing subsequent vaccine adjuvant or CTA screening formulations. Finally, dielectric property measurements were able to monitor the onset of reaction and steady-state operation. Full article

The elicitation of broadly neutralizing antibodies (bnAbs) is a major goal of vaccine design for highly mutable pathogens, such as influenza, HIV, and coronavirus. Although many rational vaccine design strategies for eliciting bnAbs have been devised, their efficacies need to be evaluated in preclinical animal models and in clinical trials. To improve outcomes for such vaccines, it would be useful to develop methods that can predict vaccine efficacies against arbitrary pathogen variants. As a step in this direction, here, we describe a simple biologically motivated model of antibody reactivity elicited by nanoparticle-based vaccines using only antigen amino acid sequences, parametrized with a small sample of experimental antibody binding data from influenza or SARS-CoV-2 nanoparticle vaccinations. Results: The model is able to recapitulate the experimental data to within experimental uncertainty, is relatively insensitive to the choice of the parametrization/training set, and provides qualitative predictions about the antigenic epitopes exploited by the vaccine, which are testable by experiment. For the mosaic nanoparticle vaccines considered here, model results suggest indirectly that the sera obtained from vaccinated mice contain bnAbs, rather than simply different strain-specific Abs. Although the present model was motivated by nanoparticle vaccines, we also apply it to a mutlivalent mRNA flu vaccination study, and demonstrate good recapitulation of experimental results. This suggests that the model formalism is, in principle, sufficiently flexible to accommodate different vaccination strategies. Finally, we show how the model could be used to rank the efficacies of vaccines with different antigen compositions. Conclusion: Overall, this study suggests that simple models of vaccine efficacy parametrized with modest amounts of experimental data could be used to compare the effectiveness of designed vaccines. Full article

The anthrax pathogen Bacillus anthracis can remain dormant as spores in soil for many years. This applies to both natural foci and to sites of anthropogenic activity such as tanneries, abattoirs, or wool factories. The A.Br.075 (A-branch) clade (also known as A.Br.Sterne) is prominent not only because it comprises several outbreak strains but even more so because spore preparations of its namesake, the Sterne strain, are counted among the most utilized anthrax animal vaccines. In this study, we genome-sequenced and analyzed 56 additional B. anthracis isolates of the A.Br.075 clade. Four of these we recently retrieved from soil samples taken from a decades-long abandoned tannery. The other 52 strains originated from our archival collection from the 20th century. Notably, the extended phylogeny of the A.Br.075 clade indicated that many of the newly added chromosomes represent basal members, some of which are among the most basal strains from this lineage. Twelve new strains populate a very deep-branching lineage we have named A.Br.Ortho-Sterne (also known as A.Br.076). A further 11 isolates amend the clade named A.Br.Para-Sterne (A.Br.078). Finally, some of the terminal clusters of the clade named A.Br.Eu-Sterne appear to be replete with (near) identical isolates, possibly a result of widespread use of the Sterne vaccine and of its re-isolation from vaccination-related animal anthrax outbreaks. From the accrued new phylogenetic information, we designed and tested a variety of new SNP-PCR assays for rapid and facile genotyping of unassigned B. anthracis genomes. Lastly, the successful isolation of live B. anthracis from a long-abandoned tannery reemphasizes the need for continued risk awareness of such sites. Full article

Recoding strategies have emerged as a promising approach for developing safer and more effective vaccines by altering the genetic structure of microorganisms, such as viruses, without changing their proteins. This method enhances vaccine safety and efficacy while minimizing the risk of reversion to virulence. Recoding enhances the frequency of CpG dinucleotides, which in turn activates immune responses and ensures a strong attenuation of the pathogens. Recent advancements highlight synonymous recoding’s potential, offering improved genetic stability and immunogenicity compared to traditional methods. Live vaccines attenuated using classical methods pose a risk of reversion to virulence and can be time-consuming to produce. Synonymous recoding, involving numerous codon alterations, boosts safety and vaccine stability. One challenge is balancing attenuation with yield; however, innovations like Zinc-finger antiviral protein (ZAP) knockout cell lines can enhance vaccine production. Beyond viral vaccines, recoding can apply to bacterial vaccines, as exemplified by modified Escherichia coli and Streptococcus pneumoniae strains, which show reduced virulence. Despite promising results, challenges like ensuring genetic stability, high yield, and regulatory approval remain. Briefly, ongoing research aims to harness these innovations for comprehensive improvements in vaccine design and deployment. In this commentary, we sought to further engage the community’s interest in this elegant approach by briefly highlighting its main advantages, disadvantages, and future prospects. Full article

Nano-oncologic vaccines represent a groundbreaking approach in the field of cancer immunotherapy, leveraging the unique advantages of nanotechnology to enhance the effectiveness and specificity of cancer treatments. These vaccines utilize nanoscale carriers to deliver tumor-associated antigens and immunostimulatory adjuvants, facilitating targeted immune activation and promoting robust antitumor responses. By improving antigen presentation and localizing immune activation within the tumor microenvironment, nano-oncologic vaccines can significantly increase the efficacy of cancer immunotherapy, particularly when combined with other treatment modalities. This review highlights the mechanisms through which nano-oncologic vaccines operate, their potential to overcome existing limitations in cancer treatment, and ongoing advancements in design. Additionally, it discusses the targeted delivery approach, such as EPR effects, pH response, ultrasonic response, and magnetic response. The combination therapy effects with photothermal therapy, radiotherapy, or immune checkpoint inhibitors are also discussed. Overall, nano-oncologic vaccines hold great promise for changing the landscape of cancer treatment and advancing personalized medicine, paving the way for more effective therapeutic strategies tailored to individual patient needs. Full article

Background/Objective: Cationic polymers were shown to assemble with negatively charged proteins yielding nanoparticles (NPs). Poly-diallyl-dimethyl-ammonium chloride (PDDA) combined with ovalbumin (OVA) yielded a stable colloidal dispersion (OVA/PDDA-NPs) eliciting significant anti-OVA immune response. Dendritic cells (DCs), as sentinels of foreign antigens, exert a crucial role in the antigen-specific immune response. Here, we aimed to evaluate the involvement of DCs in the immune response induced by OVA/PDDA. Methods: In vivo experiments were used to assess the ability of OVA/PDDA-NPs to induce anti-OVA antibodies by ELISA, as well as plasma cells and memory B cells using flow cytometry. Additionally, DC migration to draining lymph nodes following OVA/PDDA-NP immunization was evaluated by flow cytometry. In vitro experiments using bone marrow-derived DCs (BM-DCs) were used to analyze the binding and uptake of OVA/PDDA-NPs, DC maturation status, and their antigen-presenting capacity. Results: Our data confirmed the potent effect of OVA/PDDA-NPs inducing anti-OVA IgG1 and IgG2a antibodies with increased CD19⁺CD138⁺ plasma cells and CD19⁺CD38⁺CD27⁺ memory cells in immunized mice. OVA/PDDA-NPs induced DC maturation and migration to draining lymph nodes. The in vitro results showed higher binding and the uptake of OVA/PDDA-NPs by BM-DCs. In addition, the NPs were able to induce the upregulation of costimulatory and MHC-II molecules on DCs, as well as TNF-α and IL-12 production. Higher OVA-specific T cell proliferation was promoted by BM-DCs incubated with OVA/PDDA-NPs. Conclusions: The data showed the central role of DCs in the induction of antigen-specific immune response by OVA-PDDA-NPs, thus proving that these NPs are a potent adjuvant for subunit vaccine design. Full article

This study aimed to identify if sensor technology could be used to detect sickness-type signs (caused by a live vaccine) in laying hens compared to physiological and clinical sign scoring and behaviour observation. The experiment comprised 5 replicate batches (4 hens and 12 days per batch) using previously non-vaccinated hens (n = 20). Hens were moved on day 1 to a large experimental room with various designated zones (e.g., litter, perches, nest box), where they wore two sensors (FitBark, TrackLab). Saline was applied using ocular and nasal drops on day 3 as a control. A live vaccine (Infectious Laryngotracheitis, ILT, vaccine), applied using the same method on day 6, was used to induce mild respiratory and other responses. Physiological and clinical signs, and behaviour from videos were also recorded by a single observer. There were significant changes in body weight (p < 0.001), feed intake (p = 0.031), cloacal temperature (p < 0.001) and three out of five clinical signs (ocular discharge (p < 0.001), conjunctivitis (p < 0.001) and depression (p = 0.009)) over days. A significant decrease (p < 0.001) in activity level (FitBark) and distance travelled (both sensors) were identified over the study days, and activity and distance travelled were highly significantly associated (p < 0.001) with total clinical scores, with hens showing reduced activity and distance travelled with worsening total clinical scores. With behaviour observations from videos, the proportions of sitting, foraging and feeding behaviours (p = 0.044, 0.036 and 0.004, respectively), the proportion of total visit duration to the litter zone (p < 0.001) and perch (p = 0.037) with TrackLab and the proportions of visit counts of hens in the litter zone (p = 0.012) from video scanning changed significantly with days. This study suggests that the vaccine challenge caused associated changes in clinical/physiological signs and activity/distance travelled data from the sensors. Sensors may have a role in detecting changes in activity and movement in individual hens indicative of health or welfare problems. Full article

Background/Objectives: Qualitative research suggests there may be identifiable characteristics that form a health professional (HCP) archetype associated with habitual seasonal influenza vaccination (SIV). However, the validity of this archetype requires further investigation, ideally within a theoretical framework that can elucidate this association and its generalisability to other vaccines. This study aims to confirm key HCP archetype characteristics associated with SIV, as informed by prior qualitative research findings, and test the generalisability of the association between this archetype and SIV to COVID-19 vaccine acceptance. Method: A cross-sectional survey was designed and distributed to an Australian HCP sample consisting of practicing nurses, midwives, pharmacists, and medical practitioners. The anonymous online survey measured key characteristics that predict vaccination behaviour and intention. Results: Most participants (n = 173) demonstrated habitual SIV behaviour (77.91%) associated with the intention to vaccinate in the future. Survey findings supported the HCP archetype, as key constructs were associated with vaccination intention and behaviour, including heightened professional responsibility, vaccine confidence, and protection of self and patients. Furthermore, results suggested progressing vaccination intention to behaviour, overcoming vaccine complacency, is possible through the provision of free, accessible vaccination services. These critical factors were broadly generalisable to the COVID-19 vaccine. Conclusions: A vaccination-positive HCP archetype, supported by access to free, convenient vaccination services, was associated with the likelihood of future vaccination behaviour, including in future pandemic response scenarios. However, it will be important to ensure that HCP vaccine knowledge gaps are minimised to enhance trust in this cohort to enable broad success. Full article

Background: The current H3N2 influenza subunit vaccine exhibits weak immunogenicity, which limits its effectiveness in preventing and controlling influenza virus infections. Methods: In this study, we aimed to develop a T4 phage-based nanovaccine designed to enhance the immunogenicity of two antigens by displaying the HA1 and M2e antigens of the H3N2 influenza virus on each phage nanoparticle. Specifically, we fused the Soc protein with the HA1 antigen and the Hoc protein with the M2e antigen, assembling them onto a T4 phage that lacks Soc and Hoc proteins (Soc⁻Hoc⁻T4), thereby constructing a nanovaccine that concurrently presents both HA1 and M2e antigens. Results: The analysis of the optical density of the target protein bands indicated that each particle could display approximately 179 HA1 and 68 M2e antigen molecules. Additionally, animal experiments demonstrated that this nanoparticle vaccine displaying dual antigen clusters induced a stronger specific immune response, higher antibody titers, a more balanced Th1/Th2 immune response, and enhanced CD4⁺ and CD8⁺ T cell effects compared to immunization with HA1 and M2e antigen molecules alone. Importantly, mice immunized with the T4 phage displaying dual antigen clusters achieved full protection (100% protection) against the H3N2 influenza virus, highlighting its robust protective efficacy. Conclusions: In summary, our findings indicate that particles based on a T4 phage displaying antigen clusters exhibit ideal immunogenicity and protective effects, providing a promising strategy for the development of subunit vaccines against various viruses beyond influenza. Full article

Background/Objectives: Approved mRNA vaccines commonly use sequences modified with pseudouridine to enhance translation efficiency and mRNA stability. However, this modification can result in ribosomal frameshifts, reduced immunogenicity, and higher production costs. This study aimed to explore the potential of unmodified mRNA sequences for varicella-zoster virus (VZV) and evaluate whether codon optimization could overcome the limitations of pseudouridine modification. Methods: We utilized artificial intelligence (AI) to design several unmodified gE mRNA sequences for VZV, considering factors such as codon preference and secondary structure. The optimized mRNA sequences were assessed for protein expression levels in vitro and were subsequently used to develop a vaccine, named Vac07, encapsulated in a lipid nanoparticle (LNP) delivery system. The immunogenicity of Vac07 was evaluated in mice. Results: Codon-optimized mRNA sequences showed significantly higher protein expression levels in vitro compared to wild-type (WT) sequences. Vaccination with Vac07 demonstrated immunogenicity in mice that was comparable to, or even superior to, the licensed Shingrix vaccine, characterized by a stronger Th1-biased antibody response and a slightly more robust Th1-type cellular response. Conclusions: Codon-optimized unmodified mRNA sequences may also represent a viable approach for mRNA vaccine development. These optimized sequences have the potential to lower production costs while possibly enhancing the immunogenicity of mRNA vaccines. Vac07, developed using this method, shows promise as a potentially more efficient and cost-effective mRNA vaccine candidate for VZV. Full article

During the last 100 years, vaccine development has evolved from an empirical approach to one of the more rational vaccine designs where the careful selection of antigens and adjuvants is key to the desired efficacy for challenging pathogens and/or challenging populations. To improve immunogenicity while maintaining a favorable reactogenicity and safety profile, modern vaccine design must consider factors beyond the choice of target antigen alone. With new vaccine technologies currently emerging, it will be possible to custom-design vaccines for optimal efficacy in groups of people with different responses to vaccination. It should be noted that after a fairly long period of overwhelming dominance of papers devoted to subunit plague vaccines, materials devoted to the development of live plague vaccines have increasingly been published. In this review, we present our opinion on reasonable tactics for the development and application of live, safe, and protective human plague vaccines causing an enhanced duration of protection and breadth of action against various virulent strains in vaccination studies representing different ages, genders, and nucleotide polymorphisms of the genes responsible for immune response. Full article

Background: COVID-19 vaccination uptake is associated with demographic characteristics such as age, sex, and ethnicity-race in the United States (U.S.). Prior research predominantly analyzed COVID-19 vaccination uptake unidimensionally, limiting insights into multidimensional demographic inequalities. Multidimensional studies provide a closer insight into vaccination inequality and assist in designing more effective vaccination strategies. Objectives: Review descriptive studies of the COVID-19 vaccination uptake across combinations of at least two of the three key demographic characteristics: age, sex, and ethnicity-race in the U.S. Methods: A systematic review was performed using the Joanna Briggs Institute methodology and adhering to the PRISMA-ScR principles for reporting. Six impartial reviewers examined all of the papers. The data were obtained using a tailored data extraction template. Results: A total of 2793 records were initially downloaded, 461 of them were dropped for duplication, and 2332 were reviewed. Based on the title and abstract reviews, 2115 records were excluded. After reviewing the full text of the remaining records, 212 more records were excluded. The remaining six records were reviewed to identify and compare their population, study period, data, the studied dose number, methodology, and results. Conclusions: Multidimensional COVID-19 vaccine uptake analyses are rare and mostly focused on the dose-one vaccination. Improving researchers’ access to immunization registry data while preserving data security is a prerequisite for such analyses. Full article

Background: In the past decade, immunotherapy has become a major choice for the treatment of lung cancer, yet its therapeutic efficacy is still relatively limited due to the various immune escape mechanisms of tumors. Based on this, we introduce Neo-BCV, a novel bacterial composite vaccine designed to enhance immune responses against lung cancer. Methods: We investigated the immune enhancing effect of Neo-BCV through in vivo and in vitro experiments, including flow cytometry, RNA-seq, and Western blot. Results: We have demonstrated that Neo-BCV can promote Dendritic cells (DCs) maturation and induce DCs differentiation into pro-inflammatory subgroups, significantly enhancing cytotoxic T lymphocyte (CTL)-mediated anti-tumor responses. Transcriptome sequencing revealed that Neo-BCV exerts its effects by specifically inhibiting the JAK2-STAT3 signaling pathway, a crucial regulator of cancer progression, metabolism, and inflammation. Moreover, Neo-BCV significantly improved the immune microenvironment in both tumor and spleen tissues without inducing notable toxic effects in major organs. Conclusions: These findings highlight Neo-BCV’s potential as a safe and effective therapeutic strategy, offering a novel avenue for clinical translation in lung cancer immunotherapy. Full article

Background: During the COVID-19 pandemic, migrant populations remained under-immunized due to limited access to health care, language barriers, and vaccine hesitancy. The USAID-funded MOMENTUM Routine Immunization Transformation and Equity project supported the government in collaborating with various local health and non-health partners to identify and vaccinate migrants. This case study examines the roles of project partners and the strategies each entity implemented to increase COVID-19 vaccine uptake among migrants, as well as the perceptions regarding the effectiveness of these strategies. Methods: We designed a qualitative explanatory case study guided by the Behavioral and Social Drivers framework and RE-AIM implementation science frameworks. We conducted 31 focus group discussions and 50 in-depth interviews with migrants, project partners, community leaders, and government stakeholders in Tamil Nadu and Punjab. Results: In both states, partnerships with health departments, private employers, and community-based organizations were essential for identifying and vaccinating un- and under-vaccinated migrant groups. In Tamil Nadu, collaboration with the Department of Labor and mobile medical units facilitated vaccination camps at construction sites. In Punjab, religious institutions organized sessions at places of worship, and the Border Security Force enabled health workers to reach migrants living near the border. In both states, key strategies—involving influencers to discuss the importance of vaccine safety and value, bringing vaccination services to migrants’ workplaces and homes at flexible times and mandating workplace vaccination to encourage vaccination—shifted perceptions towards vaccination and increased vaccine uptake among migrants. Conclusions: The strategies and partnerships identified in this study highlight the broader implications for future public health interventions, demonstrating that collaboration with the private sector and faith-based organizations can enhance routine immunization efforts, particularly when localized to organizations that understand community needs and can address specific barriers and motivators. Full article

Background/Objectives Bacterial ghosts (BGs), non-living empty envelopes of bacteria, are produced either through genetic engineering or chemical treatment of bacteria, retaining the shape of their parent cells. BGs are considered vaccine candidates, promising delivery systems, and vaccine adjuvants. The practical use of BGs in vaccine development for humans is limited because of concerns about the preservation of viable bacteria in BGs. Methods: To increase the efficiency of Klebsiella pneumoniae BG formation and, accordingly, to ensure maximum killing of bacteria, we exploited previously designed plasmids with the lysis gene E from bacteriophage φX174 or with holin–endolysin systems of λ or L-413C phages. Previously, this kit made it possible to generate bacterial cells of Yersinia pestis with varying degrees of hydrolysis and variable protective activity. Results: In the current study, we showed that co-expression of the holin and endolysin genes from the L-413C phage elicited more rapid and efficient K. pneumoniae lysis than lysis mediated by only single gene E or the low functioning holin–endolysin system of λ phage. The introduction of alternative lysing factors into K. pneumoniae cells instead of the E protein leads to the loss of the murein skeleton. The resulting frameless cell envelops are more reminiscent of bacterial sacs or bacterial skins than BGs. Although such structures are less naive than classical bacterial ghosts, they provide effective protection against infection by a hypervirulent strain of K. pneumoniae and can be recommended as candidate vaccines. For our vaccine candidate generated using the O1:K2 hypervirulent K. pneumoniae strain, both safety and immunogenicity aspects were evaluated. Humoral and cellular immune responses were significantly increased in mice that were intraperitoneally immunized compared with subcutaneously vaccinated animals (p < 0.05). Conclusions: Therefore, this study presents novel perspectives for future research on K. pneumoniae ghost vaccines. Full article