Stable Vaccine Research Articles

The Role of Freeze-Drying as a Multifunctional Process in Improving the Properties of Hydrogels for Medical Use

Background/Objectives: Freeze-drying is a dehydration method that extends the shelf life and stability of drugs, vaccines, and biologics. Recently, its role has expanded beyond preservation to improve novel pharmaceuticals and their carriers, such as hydrogels, which are widely studied for both drug delivery and wound healing. The main aim of this study was to explore the multifunctional role of freeze-drying in improving the physicochemical properties of sodium alginate/poly(vinyl alcohol)-based hydrogels for medical applications. Methods: The base matrix and hydrogels containing a nanocarrier-drug system, were prepared by chemical cross-linking and then freeze-dried for 24 h at −53 °C under 0.2 mBa. Key analyses included determination of gel fraction, swelling ratio, FT-IR, SEM, TG/DTG, in vitro drug release and kinetics, and cytotoxicity assessment. Results: Freeze-drying caused an increase in the gel fraction of the hydrogel with the dual drug delivery system from 55 ± 1.6% to 72 ± 0.5%. Swelling ability was pH-dependent and remained in the same range (175–282%). Thermogravimetric analysis showed that freeze-dried hydrogels exhibited higher thermal stability than their non-freeze-dried equivalents. The temperature at 10% weight loss increased from 194.0 °C to 198.9 °C for the freeze-dried drug-loaded matrix, and from 188.4 °C to 203.1 °C for the freeze-dried drug-free matrix. The average pore size of the freeze-dried hydrogels was in the range of 1.07 µm ± 0.54 to 1.74 µm ± 0.92. In vitro drug release revealed that active substances were released in a controlled and prolonged way, according to the Korsmeyer–Peppas model. The cumulative amount of salicylic acid released at pH = 9.0 after 96 h was 63%, while that of fluocinolone acetonide reached 73%. Both hydrogels were non-toxic to human fibroblast cells, maintaining over 90% cell viability after 48 h of incubation. Conclusions: The results show a high potential for commercialisation of the obtained hydrogels as medical dressings.

Glycoside-Mediated Enhancement of Stability in Aluminum Oxyhydroxide Nanoadjuvants during Freeze-Drying.

Aluminum-based adjuvants have been indispensable to vaccine potency. However, their effectiveness is difficult to maintain after freeze-drying, which limits the storage and application of aluminum-adjuvanted vaccines. In this study, the impact of freeze-drying on aluminum oxyhydroxide nanorods (AlOOH NRs) was investigated. Freeze-drying led to aggregation and resulted in the loss of the surface hydroxyl content of aluminum adjuvants. To alleviate freeze-drying-induced damage, the potency of different alkyl glycosides as protectants was further evaluated. It was demonstrated that the structural balance of the head and tail of a glycoside was more conducive to protecting AlOOH NRs from aggregation and loss of surface hydroxyl groups. These results underline the proper selection of protectants to protect adjuvants against functional defects caused by freeze-drying, which is important for the stability and efficacy of vaccines and biopharmaceutical products.

Design of cold storage as a storage space for animal vaccines at PT. XYZ

A refrigeration system is a system used to cool a room or an industrial product in the food, pharmaceutical, beverage, vegetable, fruit, and other industries to maintain product quality. One of its uses is as storage for various kinds of pharmaceutical needs, including vaccines for both animals and humans. The problem with cold storage is that existing vaccine storage has been in operation for a long time so it is necessary to study whether it is still able to maintain the vaccine storage temperature, namely -80C. The aim of designing cold storage is to maintain a stable vaccine storage temperature. Because vaccines consist of various kinds of microorganisms that are easy to activate. To maintain the quality of the vaccine, cold storage is needed. The research methodology for writing this thesis is to collect design data from one of the vaccine storage industry companies, and literature studies, then analysis of cooling load planning studies, vaccine storage capacity in cold storage measuring 10 x 10 x m 3 meters and determine the power of the cooling machine using a system. standard vapor compression cooler. The results of the analysis of the refrigeration system planning study showed that the indoor vaccine capacity was 30,600 bottles or 2056,701 lbs (822,680 kg), storage temperature -80C, cooling load 308,133 Btu/hr, or 90,283 W, this system uses R 134 A refrigeration. Using refrigerant, power compressor 23.32 kW, or 32 HP, COP 3.9.

Long-term Immunity of a Microneedle Array Patch of SARS-CoV-2 S1 Protein Subunit Vaccine Irradiated by Gamma Rays in Mice.

COVID-19 vaccines effectively prevent symptomatic infection and severe disease, including hospitalization and death. However, unequal vaccine distribution during the pandemic, especially in low- and middle-income countries, has led to the emergence of vaccine-resistant strains. This underscores the need for alternative, safe, and thermostable vaccine platforms, such as dissolved microneedle array patches (MAP) delivering a subunit vaccine, which eliminate the need for cold chain and trained healthcare personnel. This study demonstrates that the SARS-CoV-2 S1 monomer with RS09, a TLR-4 agonist peptide, serves as an optimal protein subunit immunogen. This combination stimulates a stronger S1-specific immune response, resulting in binding to the membrane-bound spike on the cell surface and ACE2-binding inhibition, compared to the monomer S1 alone or trimer S1, regardless of RS09. MAP delivery of the rS1RS09 subunit vaccine elicited higher and longer-lasting immunity compared to conventional intramuscular injection. S1-specific IgG levels remained significantly elevated for up to 70 weeks post-administration. Additionally, different doses of 5, 15, and 45 μ g of MAP vaccines induced robust and sustained Th2-prevalent immune responses, suggesting a dose-sparing effect and inducing significantly high neutralizing antibodies against the Wuhan, Delta, and Omicron variants at 15 and 45 μ g dose. Moreover, gamma irradiation as a terminal sterilization method did not significantly affect immunogenicity, with irradiated vaccines maintaining comparable efficacy to non-irradiated ones. The stability of MAP vaccines was evaluated after long-term storage at room temperature and refrigeration for 19 months, showing minimal protein degradation. Further, after an additional one-month of storage at elevated temperature (42°C), rS1RS09 in both non-irradiated and irradiated MAP degraded less than 3%, while the liquid subunit vaccine degraded over 23%. Overall, these results indicate that gamma irradiation sterilized MAP-rS1RS09 vaccines maintain stability during extended storage without refrigeration, supporting their potential for mass production and widespread use in global vaccination efforts.

Stability characterizations of feed-based bivalent vaccine containing inactivated Streptococcus agalactiae and Aeromonas hydrophila against streptococcosis and Aeromonas infections in red hybrid tilapia (Oreochromis sp.).

Feed-based bivalent vaccine (FBBV) containing killed whole organism (KWO) of Streptococcus agalactiae and Aeromonas hydrophila with 10% palm oil was previously proved to improve red hybrid tilapia's (Oreochromis sp.) immunity against streptococcosis and Aeromonas infections. This study characterized the FBBV's stability following the preparatory process and storage. The FBBV was prepared, and the KWO's stability was determined microscopically and molecularly. The efficacy of FBBV stored at room temperature (25 ± 2°C) for 0, 30 and 60 days was investigated in red hybrid tilapia. The results indicated the addition of palm oil was not affecting the KWO's structure and helping in the FBBV's pelletization. In 1g of FBBV contained 1.5 × 109 CFU/g of S. agalactiae and 4.9 × 109 CFU/g of A. hydrophila, respectively, even after 60 days of storage at room temperature. The KWO's structure in FBBV was not affected following in vitro acidic tolerance analysis, as noted from light and electron microscopies. The FBBV's carbohydrate, energy, moisture, total protein and total ash contents remained stable at 95% after 60 days of storage at room temperature, while the KWO's concentration was slightly reduced to 83.3% for S. agalactiae (1.25 × 109 CFU/g) and 80.6% for A. hydrophila (3.85 × 109 CFU/g), respectively. Fish vaccinated with FBBV that was stored for 0, 30 and 60 days did not show any significant differences (p ≥ 0.05) in the relative percent survival when challenged with pathogenic Streptococcus spp. and Aeromonas spp. These findings suggested that the FBBV is a stable vaccine, which underscores its potential application as aquatic vaccines in aquaculture.

Current regulatory requirements for stability studies of biological medicinal products: a review

INTRODUCTION. The stability assessment of biological medicinal products (BMPs) requires special approaches and regulatory requirements. Therefore, BMPs require relevant national guidelines, which are an important prerequisite for the assurance of the safe and effective use of BMPs.AIM. This study aimed to analyse national and international requirements for the stability assessment of BMPs in order to use the results to inform future development of a unified regulatory approach to estimating and confirming shelf-life periods for BMPs.DISCUSSION. Most biotechnological medicinal products (BTMPs) are proteins and are highly sensitive to environmental factors by nature. Therefore, the shelf life of a BTMP is established on the basis of real-time stability studies. Stability testing under accelerated and stress conditions is conducted to support shelf-life claims and to characterise the mechanism of protein structure degradation. The results of accelerated and stress studies can be used to select the most sensitive stability-indicating parameters and testing methods. National and international regulatory authorities have developed specialised guidelines for stability studies of BMPs of various origins, and the stability assessment approaches in the regulatory system of the Eurasian Economic Union (EAEU) are harmonised with international standards. Special considerations associated with the stability of vaccines imply that stability studies of vaccines should not only establish shelf life but also investigate stability after reconstitution and after short-term temperature excursions from the recommended cold-chain conditions.CONCLUSIONS. Special stability testing considerations for various groups of BMPs (including BTMPs and immunobiologicals) indicate the need to develop and improve the system of requirements for BMP stability assessment. This will facilitate the optimisation of the life cycle of BMPs in the Russian Federation and the other EAEU member states.

Improving flu vaccination rates among adult patients with cancer at Kaiser Permanente.

326 Background: Vaccines protect cancer patients from developing severe illness, hospitalization, and death. At Kaiser Permanente (KP) South Sacramento Medical Center (KPSSC), oncology patients on active chemotherapy had an overall flu vaccination rate of 13% between September 1, 2022, and December 1, 2022. Our aim was to increase this rate to 33% during the 2023 flu season. Methods: In conjunction with the ASCO Quality Training Program, we applied quality improvement initiatives to improve flu vaccination. Our population of interest included adult cancer patients on active chemotherapy at KPSCC. We evaluated the barriers to vaccination assessment by distributing surveys to infusion nurses. We performed three Plan-Do-Study-Act (PDSA) cycles for quality improvement and monitored flu vaccination rates. Cycle 1 (9/11/2023 to 11/5/2023): We distributed the ASCO flu vaccine handout at oncology clinic. We had medical assistants and infusion nurses administer flu vaccines during clinic visits and chemotherapy sessions. Cycle 2 (11/6/2023 to 11/21/2023): We added the vaccine handout in Chinese and Spanish and updated our receptionists’ script to strongly encourage patients to receive flu vaccine. Cycle 3 (11/22/2023 to 12/6/2023): KP flu clinic set up an onsite flu vaccine cart one half day per week in the oncology clinic. Results: Barriers to vaccination assessment in the clinic included lack of time (60%), difficulty remembering to ask (10%), and non-influenza season (10%). Our interventions resulted in an increased flu vaccination rate from 13% in 2022 to 36% in 2023. During cycle 1, 298 out of 615 patients received their vaccine (48.5%). During cycle 2, 16 out of 118 patients received their vaccine (13.6%). PDSA cycle 3 resulted in 14 out of 178 patients receiving their vaccine (7.9%). Conclusions: Promoting vaccine awareness via active engagement with nurses and medical assistants early on and having onsite vaccine availability in the oncology clinic were keys to improve the overall flu vaccination rate. While most vaccines were administered at the beginning of flu season, the addition of language-tailored vaccine handouts and having an onsite vaccine cart towards the end of the season did result in late season vaccinations. Our findings do support the importance of providing timely vaccine information in the oncology clinic. Our future goal is to expand these efforts to other KP Northern California oncology centers to establish stable onsite vaccine availability in clinics and include additional vaccine types.

New Engineered-Chimeric Botulinum Neurotoxin Mutant Acts as an Effective Bivalent Vaccine Against Botulinum Neurotoxin Serotype A and E.

Botulinum neurotoxins (BoNTs), including serotypes A and E, are potent biotoxins known to cause human poisoning. In addition to the critical protective antigen found in the full BoNT molecule, the receptor binding domain (Hc domain), BoNTs also harbour another essential protective antigen-the light chain-translocation domain (L-HN domain). Leveraging these pivotal protective antigens, we genetically engineered a series of inactivated chimeric molecules incorporating L-HN and Hc domains of BoNT/A and E. The structure of these chimeric molecules, mirror BoNT/A and E, but are devoid of enzyme activity. Experimental findings demonstrated that a lead candidate mEL-HN-mAHc harnessing the inactivated protease LCHN/E with the mutated gangliosides binding site Hc/A (mE-mA) elicited robust immune protection against BoNT/A and E simultaneously in a mouse model, requiring low immune dosages and minimal immunisations. Moreover, mE-mA exhibited high protective efficacy against BoNT/A and E in guinea pigs and New Zealand white rabbits, resulting in elevated neutralising antibody titres. Furthermore, mE-mA proved to be a more stable and safer vaccine compared to formaldehyde-inactivated toxoid. Our data underscore the genetically engineered mE-mA as a highly effective bivalent vaccine against BoNT/A and E, paving the way for the development of polyvalent vaccines against biotoxins.

Comprehensive Optimization of a Freeze-Drying Process Achieving Enhanced Long-Term Stability and In Vivo Performance of Lyophilized mRNA-LNPs

The success of mRNA vaccines against SARS-CoV-2 has prompted interest in mRNA-based pharmaceuticals due to their rapid production, adaptability, and safety. Despite these advantages, the inherent instability of mRNA and its rapid degradation in vivo underscores the need for an encapsulation system for the administration and delivery of RNA-based therapeutics. Lipid nanoparticles (LNPs) have proven the most robust and safest option for in vivo applications. However, the mid- to long-term storage of mRNA-LNPs still requires sub-zero temperatures along the entire chain of supply, highlighting the need to develop alternatives to improve mRNA vaccine stability under non-freezing conditions to facilitate logistics and distribution. Lyophilization presents itself as an effective alternative to prolong the shelf life of mRNA vaccines under refrigeration conditions, although a complex optimization of the process parameters is needed to maintain the integrity of the mRNA-LNPs. Recent studies have demonstrated the feasibility of freeze-drying LNPs, showing that lyophilized mRNA-LNPs retain activity and stability. However, long-term functional data remain limited. Herein, we focus on obtaining an optimized lyophilizable mRNA-LNP formulation through the careful selection of an optimal buffer and cryoprotectant and by tuning freeze-drying parameters. The results demonstrate that our optimized lyophilization process maintains LNP characteristics and functionality for over a year at refrigerated temperatures, offering a viable solution to the logistical hurdles of mRNA vaccine distribution.

Tyrosinase-Mediated Conjugation for Antigen Display on Ferritin Nanoparticles.

Ferritin (Ft) nanoparticles have become versatile platforms for displaying antigens, being a promising technology for vaccine development. While genetic fusion has traditionally been the preferred method for antigen display, concerns about improper folding and steric hindrance that may compromise vaccine efficacy or stability have prompted alternative approaches. Bioconjugation offers the advantage of preserving native protein structure and function, with recent advancements improving efficiency and specificity. In this study, we used tyrosinase (TYR) to bioconjugate the receptor binding domain of the SARS-CoV-2 spike protein, tagged with a tyrosine (RBD-Y), to native cysteines on Ft, resulting in RBD-Y-Ft nanoparticles. We quantified available cysteines on ferritin using Ellman's assay and monitored their reduction during the reactions. Denaturing analytics (via SDS-PAGE, Western blot, and LC-TOF-MS) confirmed the formation of RBD-Y-Ft monomers with an expected molecular weight of 46 kDa. Mass photometry and HPLC estimated a molecular weight of RBD-Y-Ft nanoparticles of 680 kDa, which was higher than that of nonfunctionalized ferritin (480 kDa), indicating successful binding of up to eight RBD-Y antigens per 24-mer Ft nanoparticle. This work enhances our understanding of how Ft nanoparticles can be engineered to present antigens, leveraging them as a robust scaffold for producing tailored-made candidate vaccines in a timely manner.

Abstract B010: Design of personalized neoantigen mRNA vaccines against breast cancer patients in Pakistan based on next-generation sequencing data

Abstract Breast cancer is the most common malignancy among women in Pakistan, with an outrageous increase in the incidence and mortality rate. Because of decreased effectiveness and lower survival rates, there is an urgent need for developing novel, personalized vaccines with enhanced activity. The development of a personalized mRNA vaccine illustrates a promising approach to combating the prevalence of breast cancer. We used the whole exome sequencing (WES) data of Pakistani tumor samples to predict immunogenic neoantigens. The WES data was aligned to the GRCM39 reference genome using BWA. The genome analysis toolkit (GATK) was employed for variant calling to identify somatic mutations. Using immune-bioinformatics tools, we predicted cytotoxic CD8+ T cell epitopes and helper CD4+ T cell epitopes within the identified neoantigens and designed vaccines by assembling the fusion of CTL neoepitopes, helper sequences, and adjuvants together with linkers. The Insilco ImmSim algorithm was used to examine the immune responses of the vaccine. The vaccine design was further explored by checking its simulation effect on the immune system, its physiochemical characteristics, its binding to specific immune system molecules, and cloning into an appropriate vector. In addition, molecular docking, MD simulation, and binding free energies were performed to investigate the interaction mechanism between the construct vaccine and Toll-like receptors (TLR2, TLR4, TLR7, and TLR9).By examining these factors, we aimed to ensure the vaccine's safety, stability, and ability to bind tightly to specific immune cells (class I MHC molecules), ultimately triggering a comprehensive immune response against breast cancer cells. Citation Format: Kayode Yomi Raheem, Muhammad Muddassar. Design of personalized neoantigen mRNA vaccines against breast cancer patients in Pakistan based on next-generation sequencing data [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B010.

Novel platform for engineering stable and effective vaccines against botulinum neurotoxins A, B and E.

Botulinum neurotoxin (BoNT), produced by Clostridium botulinum, is the most toxic protein known, capable of causing severe paralysis and posing a significant bioterrorism threat due to its extreme lethality even in minute quantities. Despite this, there are currently no FDA-approved vaccines for widespread public use. To address this urgent need, we have developed an innovative vaccine platform by fusing the neuronal binding domain of BoNT/E (Hc/E) with core-streptavidin (CS), resulting in a stable CS-Hc/E vaccine. Mice vaccinated with CS-Hc/E exhibited superior antibody titers compared to those receiving Hc/E alone. To develop a trivalent vaccine against BoNT/A, BoNT/B, and BoNT/E- key contributors to the vast majority of human botulism-we conjugated CS-Hc/E with a biotinylated atoxic chimeric protein incorporating neutralizing epitopes from BoNT/A and BoNT/B. This chimeric protein includes the binding domain of BoNT/A, along with the protease-inactive light chain and translocation domains of BoNT/B. The interaction between CS and biotin formed a stable tetrameric antigen, EBA. Vaccination with EBA in mice elicited robust antibody responses and provided complete protection against lethal doses of BoNT/A, BoNT/B, and BoNT/E. Our findings highlight EBA's potential as a stable and effective broad-spectrum vaccine against BoNT. Moreover, our technology offers a versatile platform for developing multivalent, stable vaccines targeting various biological threats by substituting the BoNT domain(s) with neutralizing epitopes from other life-threatening pathogens, thereby enhancing public health preparedness and biodefense strategies.

Enhancing protective immunity against bacterial infection via coating nano-Rehmannia glutinosa polysaccharide with outer membrane vesicles.

With the coming of the post-antibiotic era, there is an increasingly urgent need for safe and efficient antibacterial vaccines. Bacterial outer membrane vesicles (OMVs) have received increased attention recently as a potential subunit vaccine. OMVs are non-replicative and contain the principle immunogenic bacterial antigen, which circumvents the safety concerns of live-attenuated vaccines. Here, we developed a novel nano-vaccine by coating OMVs onto PEGylated nano-Rehmannia glutinosa polysaccharide (pRL) in a structure consisting of concentric circles, resulting in a more stable vaccine with improved immunogenicity. The immunological function of the pRL-OMV formulation was evaluated in vivo and in vitro, and the underlying mechanism was studied though transcriptomic analysis. The pRL-OMV formulation significantly increased dendritic cell (DC) proliferation and cytokine secretion. Efficient phagocytosis of the formulation by DCs was accompanied by DC maturation. Further, the formulation demonstrated superior lymph node targeting, contributing to a potent mixed cellular response and bacterial-specific antibody response against Bordetella bronchiseptica infection. Specifically, transcriptomic analysis revealed that the immune protection function correlated with T-cell receptor signalling and Th1/Th2/Th17 differentiation, among other markers of enhanced immunological activity. These findings have implications for the future application of OMV-coated nano-carriers in antimicrobial immunotherapy.

Stability Preparedness: The Not-So-Cold Case for Innovations in Vaccine Stability Modelling and Product Release.

The rapid development of equitably accessible vaccines is paramount in addressing emerging global health challenges. The safety and efficacy of vaccines hinge significantly on their ability to remain stable from manufacturing throughout the supply chain and up to administration. Furthermore, the release of vaccines requires sufficient understanding of the stability profile to allow for expiration dating. In the event of a public health crisis, the time to generate the necessary stability data and the need for rapid product release are in direct opposition. Developing manufacturing platforms with thermostable product formulations for rapid response is therefore key to meeting CEPI's 100 Days Mission goal. This Review aims to highlight the need for stability preparedness through developing thermostable vaccine platforms and exploring innovative stability monitoring strategies that leverage advanced technologies, predictive modelling, and adaptive methodologies. By doing so, we seek to enhance the efficiency and effectiveness of stability assessments, supporting rapid development, regulatory approval, and widespread, equal distribution of vaccines-especially in an outbreak scenario. Finally, enhanced thermostability will allow for simplification across the supply chain, which will reduce the financial burden of vaccination programmes and enhance equitable access.

A New Immunogenic Structure of Polyepitopic Fusion against Leishmania major: In Silico Study.

The lack of complete protection against leishmaniasis and the challenges of anti-leishmaniasis drug treatment have made the treatment process more difficult. This study aimed to develop a new strategy for preparing a vaccine against cutaneous leishmaniasis using some of the antigenic proteins of the Leishmania parasite. This study was carried out in 2022 at Shahid Chamran University of Ahvaz, Ahvaz, Iran. After preparing suitable epitopes of the Leishmania parasite and examining their antiparasitic properties, the process of making a fusion vaccine was performed and with the help of various bioinformatics tools, physicochemical and structural properties as well as immunological and simulation properties were studied and finally optimized. Construction and cloning were performed in the E.coli K12 system and finally, the docking process was performed with Toll-like receptors (TLRs), major histocompatibility complex I (MHC-I), and MHC-II receptors. With the help of selected epitopes of the Leishmania parasite, which had a high percentage of population coverage, a stable, antigenic, and non-allergenic chimeric vaccine was predicted. The results of the structural analysis of the TLR5\vaccine complex and simulation of its molecular dynamics showed a sufficiently stable binding. It also showed good potential for stimulation and production of active B cells and memory, as well as the potential for CD8+ T, CD4+ T cell production and development of Th2 and Th1-induced immune responses. Computational results showed that the designed immunogenic structure has the potential to adequately stimulate cellular and humoral immune responses against Leishmania parasitic disease. As a result of evaluating the effectiveness of the candidate vaccine through in vivo and in vitro immunological tests, it can be suggested as a vaccine against Leishmania major.

Strategic deactivation of mRNA COVID-19 vaccines: New applications for siRNA therapy and RIBOTACs.

The rapid development and authorization of messenger ribonucleic acid (mRNA) vaccines by Pfizer-BioNTech (BNT162b2) and Moderna (mRNA-1273) in 2020 marked a significant milestone in human mRNA product application, overcoming previous obstacles such as mRNA instability and immunogenicity. This paper reviews the strategic modifications incorporated into these vaccines to enhance mRNA stability and translation efficiency, such as the inclusion of nucleoside modifications and optimized mRNA design elements including the 5' cap and poly(A) tail. We highlight emerging concerns regarding the wide systemic biodistribution of these mRNA vaccines leading to prolonged inflammatory responses and other safety concerns. The regulatory framework guiding the biodistribution studies is pivotal in assessing the safety profiles of new mRNA formulations in use today. The stability of mRNA vaccines, their pervasive distribution, and the longevity of the encapsulated mRNA along with unlimited production of the damaging and potentially lethal spike (S) protein call for strategies to mitigate potential adverse effects. Here, we explore the potential of small interfering RNA (siRNA) and ribonuclease targeting chimeras (RIBOTACs) as promising solutions to target, inactivate, and degrade residual and persistent vaccine mRNA, thereby potentially preventing uncontrolled S protein production and reducing toxicity. The targeted nature of siRNA and RIBOTACs allows for precise intervention, offering a path to prevent and mitigate adverse events of mRNA-based therapies. This review calls for further research into siRNA and RIBOTAC applications as antidotes and detoxication products for mRNA vaccine technology.

Monitoring the VDPV2 outbreak in Egypt during 2020–2021 highlights the crucial role of environmental surveillance and boosting immunization in combating Poliovirus

BackgroundPoliovirus is a highly infectious enterovirus (EV) that primarily affects children and can lead to lifelong paralysis or even death. Vaccine-derived polioviruses (VDPVs) are a great threat since they are derived from the attenuated virus in the Oral Poliovirus Vaccine (OPV) and can mutate to a more virulent form. The purpose of this study was to identify VDPV serotype 2 through the year 2020–2021 via surveillance of sewage samples collected from different localities and governorates in Egypt and stool specimens from Acute Flaccid Paralysis (AFP) cases. Both were collected through the national poliovirus surveillance system and according to the guidelines recommended by the WHO.MethodsA total of 1266 sewage samples and 3241 stool samples from January 2020 to December 2021 were investigated in the lab according to World Health Organization (WHO) protocol for the presence of Polioviruses by cell culture, molecular identification of positive isolates on L20B cell line was carried out using real-time polymerase chain reactions (RT-PCR). Any positive isolates for Poliovirus type 2 and isolates suspected of Vaccine Derived Poliovirus Type 1 and type 3 screened by (VDPV1) or Vaccine Poliovirus Type 3 (VDPV3) assay in RT-PCR were referred for VP1 genetic sequencing.ResultsThe outbreak was caused by circulating VDPV2 (cVDPV2) strains started in January 2021. By the end of February 2021, a total of 11 cVDPV2s were detected in sewage samples from six governorates confirming the outbreak situation. One additional cVDPV2 was detected later in the sewage sample from Qena (June 2021). The first and only re-emergence of VDPV2 in stool samples during the outbreak was in contact with Luxor in June 2021. By November 2021, a total of 80 VDPVs were detected. The Egyptian Ministry of Health and Population (MOHP), in collaboration with the WHO, responded quickly by launching two massive vaccination campaigns targeting children under the age of five. Additionally, surveillance systems were strengthened to detect new cases and prevent further spread of the virus.ConclusionThe continued threat of poliovirus and VDPVs requires ongoing efforts to prevent their emergence and spread. Strategies such as improving immunization coverage, using genetically stable vaccines, and establishing surveillance systems are critical to achieving global eradication of poliovirus and efficient monitoring of VDPVs outbreaks.

Advancements in Newcastle Disease Vaccination: Evaluating Traditional and Thermostable Vaccines for Enhanced Control and Efficacy

Newcastle disease (ND) is a critical viral disease in poultry, affecting various avian species worldwide and causing substantial economic losses annually in commercial and backyard poultry operations. Despite its global prevalence, ND can be controlled through proper vaccination and biosecurity management. Over the past 60-65 years, both live attenuated and inactivated ND virus vaccines have been extensively used to mitigate the economic impact of ND. Although live vaccines demonstrate high efficacy against the disease, achieving comprehensive control of ND outbreaks and their financial consequences remains challenging. The primary limitation of most commercially available live vaccines is their heat sensitivity, necessitating a cold chain for quality maintenance, which poses difficulties in village conditions or remote areas of developing tropical countries. This review discusses various methods of ND vaccine administration, their efficacy, and immunogenicity, focusing on the efficacy and stability of thermostable ND vaccines. A thorough understanding of these factors is essential for the long-term control and eradication of ND.

Enhancing Vaccine Efficacy and Stability: A Review of the Utilization of Nanoparticles in mRNA Vaccines.

The development of vaccines has entered a new era with the advent of nanotechnology, particularly through the utilization of nanoparticles. This review focuses on the role of nanoparticles in enhancing the efficacy and stability of mRNA vaccines. Nanoparticles, owing to their unique properties such as high surface area, tunable size, and their ability to be functionalized, have emerged as powerful tools in vaccine development. Specifically, lipid nanoparticles (LNPs) have revolutionized the delivery of mRNA vaccines by protecting the fragile mRNA molecules and facilitating their efficient uptake by cells. This review discusses the various types of nanoparticles employed in mRNA vaccine formulations, including lipid-based, polymer-based, and inorganic nanoparticles, highlighting their advantages and limitations. Moreover, it explores the mechanisms by which nanoparticles improve immune responses, such as enhanced antigen presentation and the prolonged release of mRNA. This review also addresses the challenges and future directions in nanoparticle-based vaccine development, emphasizing the need for further research to optimize formulations for broader applications. By providing an in-depth analysis of the current advancements in and potential of nanoparticles in mRNA vaccines, this review aims to shed light on their critical role in combating infectious diseases and improving public health outcomes.

Advances in Engineering Circular RNA Vaccines.

Engineered circular RNAs (circRNAs) are a class of single-stranded RNAs with head-to-tail covalently linked structures that integrate open reading frames (ORFs) and internal ribosome entry sites (IRESs) with the function of coding and expressing proteins. Compared to mRNA vaccines, circRNA vaccines offer a more improved method that is safe, stable, and simple to manufacture. With the rapid revelation of the biological functions of circRNA and the success of Severe Acute Respiratory Coronavirus Type II (SARS-CoV-2) mRNA vaccines, biopharmaceutical companies and researchers around the globe are attempting to develop more stable circRNA vaccines for illness prevention and treatment. Nevertheless, research on circRNA vaccines is still in its infancy, and more work and assessment are needed for their synthesis, delivery, and use. In this review, based on the current understanding of the molecular biological properties and immunotherapeutic mechanisms of circRNA, we summarize the current preparation methods of circRNA vaccines, including design, synthesis, purification, and identification. We discuss their delivery strategies and summarize the challenges facing the clinical application of circRNAs to provide references for circRNA vaccine-related research.