The immunological and pharmacokinetic evaluation of Lipid-PLGA hybrid nanoparticle-based oxycodone vaccines.

The current opioid epidemic is one of the most profound public health crises facing the United States. Despite that it has been under the spotlight for years, available treatments for opioid use disorder (OUD) and overdose are limited to opioid receptor ligands such as the agonist methadone and the overdose reversing drugs such as naloxone. Vaccines are emerging as an alternative strategy to combat OUD and prevent relapse and overdose. Most vaccine candidates consist of a conjugate structure containing the target opioid attached to an immunogenic carrier protein. However, conjugate vaccines have demonstrated some intrinsic shortfalls, such as fast degradation and poor recognition by immune cells. To overcome these challenges, we proposed a lipid-PLGA hybrid nanoparticle (hNP)-based vaccine against oxycodone (OXY), which is one of the most frequently misused opioid analgesics. The hNP-based OXY vaccine exhibited superior immunogenicity and pharmacokinetic efficacy in comparison to its conjugate vaccine counterpart. Specifically, the hNP-based OXY vaccine formulated with subunit keyhole limpet hemocyanin (sKLH) as the carrier protein and aluminum hydroxide (Alum) as the adjuvant (OXY-sKLH-hNP(Alum)) elicited the most potent OXY-specific antibody response in mice. The induced antibodies efficiently bound with OXY molecules in blood and suppressed their entry into the brain. In a following dose-response study, OXY-sKLH-hNP(Alum) equivalent to 60 µg of sKLH was determined to be the most promising OXY vaccine candidate moving forward. This study provides evidence that hybrid nanoparticle-based vaccines may be superior vaccine candidates than conjugate vaccines and will be beneficial in treating those suffering from OUD.

COMPARING vaccine manufacturing technologies recombinant DNA vs in vitro transcribed (IVT) mRNA.

Vaccine manufacturing fosters the prevention, control, and eradication of infectious diseases. Recombinant DNA and in vitro (IVT) mRNA vaccine manufacturing technologies were enforced to combat the recent pandemic. Despite the impact of these technologies, there exists no scientific announcement that compares them. Digital Shadows are employed in this study to simulate each technology, investigating root cause deviations, technical merits, and liabilities, evaluating cost scenarios. Under this lens we provide an unbiased, advanced comparative technoeconomic study, one that determines which of these manufacturing platforms are suited for the two types of vaccines considered (monoclonal antibodies or antigens). We find recombinant DNA technology to exhibit higher Profitability Index due to lower capital and starting material requirements, pertaining to lower Minimum Selling Price per Dose values, delivering products of established quality. However, the potency of the mRNA, the streamlined and scalable synthetic processes involved and the raw material availability, facilitate faster market penetration and product flexibility, constituting these vaccines preferable whenever short product development cycles become a necessity.

Influence of immunological awareness on enhancing the overall complying with health instructions and necessary vaccines during epidemics and pandemics.

Immunological awareness plays a pivotal role in promoting adherence to health instructions during public health emergencies. This study assessed the influence of specialized immunology education on compliance behaviors among higher education students. To assess the influence of specialized immunology education on compliance behaviors toward health instructions and necessary vaccines during epidemics and pandemics among higher education students. A cross-sectional survey was conducted among 532 students at King Faisal University, Saudi Arabia using stratified random sampling. A validated questionnaire examined demographics, health awareness, and specific immunological knowledge. Regression analysis was performed to assess predictors of compliance with health instructions. Considerable knowledge gaps were found around fundamental immunological concepts despite fair awareness about vaccines. Marked disparities existed across gender and academic disciplines. Regression modeling established specialized immunology training as a significant predictor of compliance with guidelines like masking and vaccination during epidemics (p < .001). The findings highlight the need for customized immunology curricula targeting students from nonscientific backgrounds. Incorporating immunology training in continuing education programs for healthcare professionals and public officials can further promote compliance. Multifaceted public health campaigns combining immunology education with initiatives to address socio-cultural barriers are warranted. Further research should explore sustainable educational interventions to enhance long-term retention and integration of immunology knowledge into health behaviors.

Exploring Large Language Models for Detecting Online Vaccine Reactions.

Social media offers a rich source of real-time health data, including potential vaccine reactions. However, extracting meaningful insights is challenging due to the noisy nature of social media content. This paper explores using large language models (LLMs) and prompt engineering to detect personal mentions of vaccine reactions. Different prompting strategies were evaluated on two LLM models (GPT-3.5 and GPT-4) using Reddit data focused on shingles (zoster) vaccines. Zero-shot and few-shot learning approaches with both standard and chain-of-thought prompts were compared. The findings demonstrate that GPT-based models with carefully crafted chain-of-thought prompts could identify the relevant social media posts. Few-shot learning helped GPT4 models to identify more of the marginal cases, although less precisely. The use of LLMs for classification with lightweight supervised pretrained language models (PLMs) found that PLMs outperform LLMs. However, a potential benefit in using LLMs to help identify records for training PLMs was revealed, especially to eliminate false negatives, and LLMs could be used as classifiers when insufficient data exists to train a PLM.

Seno-antigen-pulsed dendritic cell vaccine induce anti-aging immunity to improve adipose tissue senescence and metabolic abnormalities.

Anti-aging immunity induced by vaccines was recently reported to enable the elimination of senescent cells. However, the initial immune response to vaccination declines with age, and there is evidence that elderly dendritic cells (DCs) have a reduced capacity to stimulate T cells. Identification of alternative anti-aging vaccine is therefore warranted. Here, we developed a DC vaccine that delivers a cationic protein (CP) fused with the seno-antigen peptides Gpnmb (Gpnmb-CP) into DCs. The Gpnmb-CP-pulsed DC vaccine (Gpnmb-CP-DC) efficiently presented antigens and activated CD8+ T cells, leading to enhanced immune cytotoxicity and memory responses in CD8+ T cells. Thus, the targeted anti-aging immunity triggered by Gpnmb-CP-DC has the ability to selectively eliminate senescent adipocytes and effectively improve age-related metabolic abnormalities in both high-fat diet (HFD)-induced young and aged mice models, as well as in natural aging mouse model. In contrast, the Gpnmb-CP protein vaccine exhibits minimal efficacy in aged mice model. Furthermore, we observed a decreased phagocytic capacity for antigens in aging DCs, accompanied by an upregulation of the immune checkpoint PDL1 expression and a noticeable decline in activated CD8+ T cell. Hence, Gpnmb-CP-DC emerges as a promising vaccine candidate, demonstrating the capacity to induce potent anti-aging immunity, mitigating adipose tissue senescence and metabolic abnormalities, while resilient to the senescent environment of the organism.

Designing of a chimeric multiepitope vaccine against bancroftian lymphatic filariasis through immunoinformatics approaches.

The filarial worms of Wuchereria bancrofti are the primary cause of lymphatic filariasis (LF), a mosquito-borne disease among the neglected tropical parasitic diseases. Considering the global endemic consequences of the disease, there is a need to develop a successful vaccine candidate against LF. Using advanced immunoinformatics approaches, we designed two multiepitope vaccines targeting W. bancrofti's glutathione S-transferase and thioredoxin. Therefore, we predicted several MHC-1, MHC-2, and B-cell epitopes from these proteins and mapped two vaccine candidates (V1 and V2). The vaccines were subsequently employed for physicochemical analysis, structural prediction and validation, docking and normal mode analysis, codon optimization, and immune simulation. The selected MHC-1, MHC-2, and B-cell epitopes were antigenic without allergenicity or toxicity. The designed vaccines were expected to be soluble, stable proteins under physiological conditions. Compared to V2, V1's secondary and tertiary structures were simultaneously favorable, with Ramachandran plot analysis revealing 95.6% residues in favored areas. Subsequently, the molecular docking analysis indicated that the V1 had a high binding affinity for the TLR-2, TLR-4 and TLR-5, as suggested by the docking scores of -1248.7, -1038.5 and -1562.8, respectively. The NMA of these complexes further indicated their structural flexibility. Molecular dynamics simulations of V1-TLR complexes revealed V1-TLR-4 as the most stable, with the lowest free energy and minimal fluctuations, indicating the strongest binding affinity. The results of the codon optimization showed high levels of expression, with a favorable CAI score (<1.0). A three-dose vaccination analysis showed significant and persistent immunological responses, including adaptive and innate immune responses. The findings emphasize the potential of the V1 against W. bancrofti, but further validation is required through in vitro, in vivo, and clinical trials.

Timeliness for vaccination according to the expanded immunization program in children under 6 years of age in Colombia between 2014 and 2019.

The aim was to estimate the vaccination timeliness defined as the proportion of children under 6 years of age who received their immunization in the time range established by the Colombian Expanded Immunization Program (EIP). A retrospective cohort study that collected reports of vaccination opportunities between 2014 and 2019 provided by the Ministry of Health. Age, sex, city, ethnicity, health system affiliation regimen, vaccine applied, and timing of vaccination were considered for the time range under study. A total of 3,370,853 immunized children were included from all regions of the country. More than 80% of children had a timeliness to get most vaccines. The exceptions were yellow fever (17%) and seasonal influenza (42%). No differences in timeliness were found according to geographic region or by health system affiliation regime, but the average timeliness for all vaccines of children of the indigenous population (65.8% ±18.4%) was lower than that of the rest of the population (78·6% ± 19·3%) (p = 0·021). The timeliness for vaccination under the EIP of Colombia is high, with proportions of 72-96%, but intergroup differences were identified, mainly lower timeliness among indigenous people. These findings warrant improvement strategies that would guarantee the immunization of the entire child population.

Significance of VLPs in Vlp-circRNA vaccines: a vaccine candidate or delivery vehicle?

Circular RNAs (circRNAs) are a class of single-stranded RNAs with a closed loop lacking 5' and 3' ends. These circRNAs are translatable and, therefore, have a potential in developing vaccine. CircRNA vaccines have been shown to be more stable, safe, easy to manufacture and scale-up production when compared to mRNA vaccines. However, these vaccines also suffer from several drawbacks such as low circularization efficiency for longer RNA precursor and usage of lipid nano particles (LNPs) in their delivery. LNPs have been shown to require large amounts of RNA due to their indirect delivery from endosome to cytosol. Besides, individual components of LNPs provide reactogenicity. Usage of virus like particles (VLPs) can improve the increased production and targeted delivery of circRNA vaccines and show no reactogenicity. Moreover, VLPs has also been used to produce vaccines against several diseases such as hepatitis C virus (HCV) etc. In this article, we will discuss about the methods used to enhance synthesis or circularization efficiency of circRNA. Moreover, we will also discuss about the significance of VLPs as the delivery vehicle for circRNA and their possible usage as the dual vaccine.

Harnessing the potential of the NALT and BALT as targets for immunomodulation using engineering strategies to enhance mucosal uptake.

Mucosal barrier tissues and their mucosal associated lymphoid tissues (MALT) are attractive targets for vaccines and immunotherapies due to their roles in both priming and regulating adaptive immune responses. The upper and lower respiratory mucosae, in particular, possess unique properties: a vast surface area responsible for frontline protection against inhaled pathogens but also simultaneous tight regulation of homeostasis against a continuous backdrop of non-pathogenic antigen exposure. Within the upper and lower respiratory tract, the nasal and bronchial associated lymphoid tissues (NALT and BALT, respectively) are key sites where antigen-specific immune responses are orchestrated against inhaled antigens, serving as critical training grounds for adaptive immunity. Many infectious diseases are transmitted via respiratory mucosal sites, highlighting the need for vaccines that can activate resident frontline immune protection in these tissues to block infection. While traditional parenteral vaccines that are injected tend to elicit weak immunity in mucosal tissues, mucosal vaccines (i.e., that are administered intranasally) are capable of eliciting both systemic and mucosal immunity in tandem by initiating immune responses in the MALT. In contrast, administering antigen to mucosal tissues in the absence of adjuvant or costimulatory signals can instead induce antigen-specific tolerance by exploiting regulatory mechanisms inherent to MALT, holding potential for mucosal immunotherapies to treat autoimmunity. Yet despite being well motivated by mucosal biology, development of both mucosal subunit vaccines and immunotherapies has historically been plagued by poor drug delivery across mucosal barriers, resulting in weak efficacy, short-lived responses, and to-date a lack of clinical translation. Development of engineering strategies that can overcome barriers to mucosal delivery are thus critical for translation of mucosal subunit vaccines and immunotherapies. This review covers engineering strategies to enhance mucosal uptake via active targeting and passive transport mechanisms, with a parallel focus on mechanisms of immune activation and regulation in the respiratory mucosa. By combining engineering strategies for enhanced mucosal delivery with a better understanding of immune mechanisms in the NALT and BALT, we hope to illustrate the potential of these mucosal sites as targets for immunomodulation.

Pandemic Incident Management for Vaccine Safety Challenges: Victoria's Alert Advisory Group Experience.

Safe vaccines are critical for biosecurity protection, yet adverse events-rightly or wrongly attributed to immunization-potentially cause rapid loss of confidence, reduced vaccine uptake, and resurgence of preventable disease. Effective vaccine safety incident management is essential to provide assessment and lead appropriate actions to ensure vaccination programs are safe and mitigate unwarranted crisis escalation that could damage vaccine programs and the effective control of vaccine preventable disease outbreaks or pandemics. Incident management systems (IMS) are used globally to direct emergency management response, particularly for natural disasters of fire, flood, and storm. Public health is equally an emergency response and can therefore benefit from these command control constructs. While examples of IMS for outbreak response and mass immunization logistics exist, there is little to no information on their use in vaccine safety. We describe Australia's vaccine safety Alert Advisory Group establishment in Victoria during the COVID-19 pandemic and onward embedding into routine practice, anticipant of new vaccines, and the next biosecurity threat.

Self-Assembled Ferritin Nanoparticles for Delivery of Antigens and Development of Vaccines: From Structure and Property to Applications.

Ferritin, an iron storage protein, is ubiquitously distributed across diverse life forms, fulfilling crucial roles encompassing iron retention, conversion, orchestration of cellular iron metabolism, and safeguarding cells against oxidative harm. Noteworthy attributes of ferritin include its innate amenability to facile modification, scalable mass production, as well as exceptional stability and safety. In addition, ferritin boasts unique physicochemical properties, including pH responsiveness, resilience to elevated temperatures, and resistance to a myriad of denaturing agents. Therefore, ferritin serves as the substrate for creating nanomaterials typified by uniform particle dimensions and exceptional biocompatibility. Comprising 24 subunits, each ferritin nanocage demonstrates self-assembly capabilities, culminating in the formation of nanostructures akin to intricate cages. Recent years have witnessed the ascendance of ferritin-based self-assembled nanoparticles, owing to their distinctive physicochemical traits, which confer substantial advantages and wide-ranging applications within the biomedical domain. Ferritin is highly appealing as a carrier for delivering drug molecules and antigen proteins due to its distinctive structural and biochemical properties. This review aims to highlight recent advances in the use of self-assembled ferritin as a novel carrier for antigen delivery and vaccine development, discussing the molecular mechanisms underlying its action, and presenting it as a promising and effective strategy for the future of vaccine development.

Vaccines and allergy: Back to the right places.

Hypersensitivity reactions represent one of the most common causes of hesitancy for adherence to national vaccination programs. The majority of hypersensitivity reactions after vaccination are mild, and anaphylaxis is reported to be rare, although it remains challenging to estimate the frequency attributed to each single vaccine, either because of the lower number of administered doses of less common vaccines, or the administration of simultaneous vaccine in most of the vaccination programs. Although literature remains scattered, international consensus guides clinicians in identifying patients who might need the administration of vaccines in protected environments due to demonstrated hypersensitivity to vaccine components or adjuvants. Here we provide the current guidance on hypersensitivity reactions to vaccines and on vaccination of children with allergy disorders.

Description of vaccination coverage and hesitancy obtained by epidemiological survey of children born in 2017-2018, in Belo Horizonte and Sete Lagoas, Minas Gerais, Brazil.

OBJECTIVE: To describe vaccination coverage and hesitation for the basic children's schedule in Belo Horizonte and Sete Lagoas, Minas Gerais state, Brazil. METHODS: Population-based epidemiological surveys performed from 2020 to 2022, which estimated vaccine coverage by type of immunobiological product and full schedule (valid and ministered doses), according to socioeconomic strata; and reasons for vaccination hesitancy. RESULTS: Overall coverage with valid doses and vaccination hesitancy for at least one vaccine were, respectively, 50.2% (95%CI 44.1;56.2) and 1.6% (95%CI 0.9;2.7), in Belo Horizonte (n = 1,866), and 64.9% (95%CI 56.9;72.1) and 1.0% (95%CI 0.3;2.8), in Sete Lagoas (n = 451), with differences between socioeconomic strata. Fear of severe reactions was the main reason for vaccination hesitancy. CONCLUSION: Coverage was identified as being below recommended levels for most vaccines. Disinformation should be combated in order to avoid vaccination hesitancy. There is a pressing need to recover coverages, considering public health service access and socioeconomic disparities. MAIN RESULTS: Vaccination coverage of children up to 4 years old was 50.2% in Belo Horizonte, and 64.9% in Sete Lagoas. Fear of severe reactions and believing that vaccination against eradicated diseases is unnecessary were the main reasons for vaccination hesitancy. IMPLICATIONS FOR SERVICES: Recovery of high vaccination coverage among children, considering public health service access conditions and socioeconomic inequities. Acting on reasons for hesitancy that can assist in targeting actions. PERSPECTIVES: The multifactorial context of vaccination hesitancy demands the development of health education strategies to raise awareness about child immunization.

Collecting and reporting adverse events in low-income settings-perspectives from vaccine trials in the Gambia.

BACKGROUND: Despite Africa's significant infectious disease burden, it is underrepresented in global vaccine clinical trials. While this trend is slowly reversing, it is important to recognize and mitigate the challenges that arise when conducting vaccine clinical trials in this environment. These challenges stem from a variety of factors peculiar to the population and may negatively impact adverse event collection and reporting if not properly addressed. METHODS: As a team of clinical researchers working within the MRCG (Medical Research Council Unit The Gambia), we have conducted 12 phase 1 to 3 vaccine trials over the past 10 years. In this article, we discuss the challenges we face and the strategies we have developed to improve the collection and reporting of adverse events in low-income settings. OUTCOME: Healthcare-seeking behaviors in the Gambia are influenced by spiritual and cultural beliefs as well as barriers to accessing orthodox healthcare; participants in trials may resort to non-orthodox care, reducing the accuracy of reported adverse events. To address this, trial eligibility criteria prohibit self-treatment and herbal product use during trials. Instead, round-the-clock care is provided to trial participants, facilitating safety follow-up. Constraints in the healthcare system in the Gambia such as limitations in diagnostic tools limit the specificity of diagnosis when reporting adverse events. To overcome these challenges, the Medical Research Council Unit maintains a Clinical Services Department, offering medical care and diagnostic services to study participants. Sociocultural factors, including low literacy rates and social influences, impact adverse event collection. Solicited adverse events are collected during home visits on paper-based or electronic report forms. Community engagement meetings are held before each study starts to inform community stakeholders about the study and answer any questions they may have. These meetings ensure that influential members of the community understand the purpose of the study and the risks and benefits of participating in the trial. This understanding makes them more likely to support participation within their communities. CONCLUSION: Conducting ethical vaccine clinical trials in resource-limited settings requires strategies to accurately collect and report adverse events. Our experiences from the Gambia offer insights into adverse event collection in these settings.

Safety and efficacy of vaccinations in patients with multiple sclerosis: a systematic review.

OBJECTIVE: The study aims to show the efficacy/effectiveness and safety of vaccinations in patients with multiple sclerosis. MATERIALS AND METHODS: This systematic review was conducted following the guidelines of the Cochrane Collaboration and the meta-analysis of observational studies in epidemiology (MOOSE). RESULTS: At the end of the review process, 133 studies were included; the bibliographic search was conducted on PubMed/Medline and Scopus, combining free text and words. CONCLUSIONS: In general, vaccinations do not seem to aggravate multiple sclerosis (MS) or increase the probability of relapse, particularly for inactivated vaccines and, in general, for the rest of the vaccines. However, it is advisable, especially for vaccines with a live attenuated virus, to carefully evaluate the risks and benefits of these vaccinations; as regards the effectiveness in relation to the drug taken, there is great variability in response. In particular, vaccinations are less effective in patients undergoing therapy with anti-CD20 and S1P modulators. At the same time, a small response is likely to be better than none. Whenever possible, vaccinations should be offered and recommended to patients with multiple sclerosis.

Precision adjuvants for pediatric vaccines.

Elucidating optimal vaccine adjuvants for harnessing age-specific immune pathways to enhance magnitude, breadth, and durability of immunogenicity remains a key gap area in pediatric vaccine design. A better understanding of age-specific adjuvants will inform precision discovery and development of safe and effective vaccines for protecting children from preventable infectious diseases.

Vacina e tecnologia: uma ótima combinação | Coisa de Homem

Fala, Truta! Neste episódio do Coisa de Homem, vocês vão entender como tecnologia tem tudo a ver com vacina e essa combinação salva vidas! E como a gente sempre diz que o SUS é lindo, você vão conhecer mais sobre a importância da rede na imunização aqui do município de São Paulo.

Vacinômetro: 05/06/2024

Secretaria Municipal da Saúde divulga Vacinômetro com o número de doses da vacina contra Covid-19 recebidas e aplicadas até o momento no município com base da faixa etária da população.

National trends in patterns of under-vaccination in early childhood: National Immunization Survey-Child, United States, 2011-2021.

BACKGROUND: The study's objective was to examine national trends in patterns of under-vaccination in the United States. RESEARCH DESIGN AND METHODS: The National Immunization Survey-Child (NIS-Child) is an annual cross-sectional survey that collects provider-verified vaccination records from a large national probability sample of children. Records from the 2011-2021 NIS-Child were used to assess receipt of the combined 7-vaccine series by age 24 months. Based on prior work, patterns indicative of hesitancy included zero vaccines, not starting ≥1 series, and consistent vaccine-limiting. Patterns indicative of practical issues included starting all series but missing doses. Up-to-date (UTD) was defined as receiving all doses in the combined 7-vaccine series. RESULTS: The study population comprised 127,257 children. Over the observation period, patterns indicative of hesitancy significantly decreased (p-trend < 0.0001), patterns indicative of practical issues significantly decreased (p-trend < 0.0001), and UTD significantly increased (p-trend < 0.0001). In 2021, the weighted percentage in each category was as follows: probable hesitancy 6.3% (95% confidence interval [CI] 5.4%, 7.2%), probable practical issues 26.0% (95% CI 24.4%, 27.6%), and UTD 67.7% (95% CI 66.0%, 69.4%). CONCLUSION: Over an 11-year period, vaccination coverage in the United States for the combined 7-vaccine series has improved, with patterns suggestive of practical issues or hesitancy declining.