The Use of Therapy Dogs in the Pediatric COVID-19 Vaccination at the University of Puerto Rico Medical Sciences Campus.

Pet ownership and therapy dogs as companion animals and emotional support have potential health benefits. We report the experiences at a COVID-19 vaccination center after authorizing children's vaccines. When the Pfizer-BioNTech vaccine for children aged 5 to 11 years was authorized for emergency use, we adapted the center's space to receive children, adding cartoon posters and balloons and using children's adhesive bandages, among others. Located at a Campus with six health professional schools, medical students dressed as storybook or movie characters. Children were asked to make drawings during the post vaccination observation period. We incorporated therapy dogs as part of our strategy for a child-friendly center during vaccination activities. Parents expressed that the COVID-19 immunization seemed to be better accepted by children as the dogs in the center entertained them. Many children were in close contact with the dogs while receiving the shots, caressing them, or having the small dogs on their laps. Children's drawings reflected colors, flowers, families, images of happiness, dogs with their names, their own pets, and superhero characters. There were no negative images of syringes, injections, or germs. To our knowledge, this was the only vaccine center in Puerto Rico that implemented therapy dogs as a strategy to create a friendly environment for COVID 19 immunization efforts targeted for children. Based on this experience, we encourage the use of therapy dogs in other immunization activities and will further gather prospective data in the future.

Immunomodulatory effect of Lacticaseibacillus casei CB054 supplementation in calves vaccinated against infectious bovine rhinotracheitis.

Probiotics are live microorganisms that, confer health benefits to the host when supplemented in adequate amounts. They can promote immunomodulation by inducing phagocyte activity, leukocyte proliferation, antibody production, and cytokine expression. Lactic acid bacteria (BAL) are important probiotic specimens with properties that can improves ruminant nutrition, productivity and immunity. The aim of the present study was to evaluate the immunomodulatory effect of the supplementation with Lacticaseibacillus casei CB054 in calve vaccinated against bovine infectious rhinotracheitis (IBR). Calve were vaccinated with a commercial IBR vaccine, on day 0 and received a booster dose on day 21. L. casei CB054 was orally administered (4 ×109 UFC) for 35 days, while a non-supplemented control group received Phosphate Buffer Saline (PBS). Stimulation of bovine splenocytes with L. casei CB054 markedly enhanced mRNA transcription levels of cytokines IL2, IL4, IL10 and IL17 genes. Calves supplemented with L. casei CB054 showed significantly higher (p < 0.05) specific anti-BoHV-1 IgG levels, higher serum neutralization, as well as higher mRNA transcription for IL2, IL4, IL10 and IL17 genes in Peripheral Blood Mononuclear Cells (PBMCs) comparing with control calves. Supplemented calve had an average weight gain of ∼14 kg more than non-supplemented during the experimental period. These results suggest that L. casei CB054 supplementation increase immunogenicity of a commercial IBR vaccine in cattle and improve weight gain.

Mucosal immune responses and protective efficacy elicited by oral administration AMP-ZnONPs-adjuvanted inactivated H9N2 virus in chickens.

The avian influenza virus is infected through the mucosal route, thus mucosal barrier defense is very important. While the inactivated H9N2 vaccine cannot achieve sufficient mucosal immunity, adjuvants are needed to induce mucosal and systemic immunity to prevent poultry from H9N2 influenza virus infection. Our previous study found that polysaccharide from Atractylodes macrocephala Koidz binding with zinc oxide nanoparticles (AMP-ZnONPs) had immune-enhancing effects in vitro. This study aimed to evaluate the mucosal immune responses of oral whole-inactivated H9N2 virus (WIV)+AMP-ZnONPs and its impact on the animal challenge protection, and the corresponding changes of pulmonary metabolomics after the second immunization. The results showed that compared to the WIV, the combined treatment of WIV and AMP-ZnONPs significantly enhanced the HI titer, IgG and specific sIgA levels, the number of goblet cells and intestinal epithelial lymphocytes (iIELs) as well as the expression of J-chain, polymeric immunoglobulin receptor (pIgR), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α) and transforming growth factor-ß (TGF-ß). In viral attack experiments, WIV combing with AMP-ZnONPs effectively reduced lung damage and viral titers in throat swabs. Interestingly, significant changes of both the IgA intestinal immune network and PPAR pathway could also be found in the WIV+AMP-ZnONPs group compared to the non-infected group. Taken together, these findings suggest that AMP-ZnONPs can serve as a potential mucosal vaccine adjuvant, thereby avoiding adverse stress and corresponding costs caused by vaccine injection.

Evolving therapeutic interventions for the management and treatment of Alzheimer's disease.

Alzheimer's Disease (AD) patients experience diverse symptoms, including memory loss, cognitive impairment, behavioral abnormalities, mood changes, and mental issues. The fundamental objective of this review is to discuss novel therapeutic approaches, with special emphasis on recently approved marketed formulations for the treatment of AD, especially Aducanumab, the first FDA approved moiety that surpasses the blood-brain barrier (BBB) and reduces amyloid plaques in the brain, thereby reducing associated cognitive decline. However, it is still in the phase IV trial and is to be completed by 2030. Other drugs such as lecanemab are also under clinical trial and has recently been approved by the FDA and is also discussed here. In this review, we also focus on active and passive immunotherapy for AD as well as several vaccines, such as amyloid-beta epitope-based vaccines, amyloid-beta DNA vaccines, and stem cell therapy for AD, which are in clinical trials. Furthermore, ongoing pre-clinical trials associated with AD and other novel strategies such as curcumin-loaded nanoparticles, Crispr/ cas9, precision medicine, as well as some emerging therapies like anti-sense therapy are also highlighted. Additionally, we discuss some off-labeled drugs like non-steroidal anti-inflammatory drugs (NSAID), anti-diabetic drugs, and lithium, which can manage symptoms of AD and different non-pharmacological approaches are also covered which can help to manage AD. In summary, we have tried to cover all the therapeutic interventions which are available for the treatment and management of AD under sections approved, clinical phase, pre-clinical phase or futuristic interventions, off-labelled drugs, and non-pharmacological interventions for AD, offering positive findings and well as challenges that remain.

Difference in the cellular response following THP-1 derived phagocytic monocyte cells exposure to commercial aluminum-based adjuvants and aluminum-containing vaccines.

BACKGROUND: Aluminum-based adjuvants (ABAs) enhance the immune response following vaccine injection. Their mechanisms of action are not fully understood, and their bio-persistency have been described associated with long-term adverse effects. METHODS: We evaluated and compared the cellular effects of the two main ABAs and whole vaccines on ATP production, ROS generation and cytokines production (IL-6 and IL-10), using THP-1 cells. RESULTS: ABAs altered the cell energy metabolism by increasing ROS production after 24 h and reducing ATP production after 48 h. In addition, both ABAs and whole vaccines induced different kinetics of IL-6 production, whereas only ABAs induced IL-10 secretion. CONCLUSION: This study showed clearly, for a first time, a difference in cellular response to the ABAs and whole vaccines which should be taken into consideration in future studies focusing on the effect of ABA in vaccines. Future studies on ABAs should also pay attention to mitochondrial function alterations following exposure to ABA-containing vaccines.

A Versatile Nanovaccine Enhancement Strategy Based on Suction-Inspired Physical Therapy.

Vaccine technology is effective in preventing and treating diseases, including cancers and viruses. The efficiency of vaccines can be improved by increasing the dosage and frequency of injections, but it would bring an extra burden to people. Therefore, it is necessary to develop vaccine-boosting techniques with negligible side effects. Herein, we reported a cupping-inspired noninvasive suction therapy that could enhance the efficacy of cancer/SARS-CoV-2 nanovaccines. Negative pressure caused mechanical immunogenic cell death and released endogenous adjuvants. This created a subcutaneous niche that would recruit and activate antigen-presenting cells. Based on this universal central mechanism, suction therapy was successfully applied in a variety of nanovaccine models, which include prophylactic/therapeutic tumor nanovaccine, photothermal therapy induced in situ tumor nanovaccine, and SARS-CoV-2 nanovaccine. As a well-established physical therapy method, suction therapy may usher in an era of noninvasive and high-safety auxiliary strategies when combined with vaccines.

Relatório Técnico Imunização 2022

O presente documento denota o Relatório Técnico de Gestão de Imunização do Brasil, referente ao ano de 2022 – Relatório Anual Brasil 2022, no contexto da Estratégia de Cooperação do País 2022-2027 (ECP/2022-2027), promovida pelo escritório da OPAS/OMS no Brasil, e Ministério da Saúde do Brasil, como uma oportunidade de reforçar os compromissos e as alianças a fim de enfrentar os grandes desafios existentes no campo da saúde pública, especificamente na imunização e, com isso contribuir com os objetivos de recuperação das coberturas vacinais, ao longo do curso de vida. A Coordenação de Imunização da OPAS/OMS no Brasil executou ações dos componentes do Programa Nacional de Imunizações (PNI) em cooperação com o Brasil nas cinco prioridades estratégicas e áreas de foco definidas na ECP/2022-2027: 1) proteger e promover a saúde da população, centrada nas pessoas, famílias e comunidades, especialmente aquelas em situação de vulnerabilidade; 2) recuperar, melhorar e tornar mais forte os serviços de saúde e os programas prioritários impactados pela pandemia da covid-19; 3) contribuir para o desenvolvimento de um Sistema Único de Saúde (SUS) mais resiliente, equitativo e eficaz, de acordo com as necessidades de saúde da população; 4) impulsionar a pesquisa, a inovação e a geração de conhecimentos científicos e tecnológicos em saúde, incluindo aqueles voltados à pesquisa, ao desenvolvimento e à produção de medicamentos, fitoterápicos e produtos tradicionais em saúde, vacinas, biotecnológicos e tecnologias em saúde e 5) reforçar a prevenção, a preparação, a resposta oportuna e a recuperação nas emergências e nos desastres. Neste documento, será apresentada uma análise retrospectiva da situação epidemiológica das doenças preveníveis por vacinação, das estratégias de vacinação, dos riscos e impactos para 2023, bem como dos Eventos Supostamente Atribuíveis à Vacinação ou Imunização (ESAVI). Ainda, será exibido no documento a participação da OPAS/OMS Brasil na elaboração das propostas de melhorias e avanços para o PNI do Brasil e contribuições com os gestores do SUS e outros parceiros que atuam ativamente nesse propósito.

Vaccine hesitancy among physicians: a qualitative study with general practitioners and paediatricians in Austria and Germany.

OBJECTIVE: This study aims to understand reasons for vaccine hesitancy (VH) among general practioners (GPs) and paediatricians. We aim to analyse how and when the healthcare workers (HCWs) developed vaccine-hesitant views and how they transfer these to patients. DESIGN AND SETTING: Semistructured interviews with vaccine-hesitant GPs and paediatricians were conducted in Austria and Germany using an explorative qualitative research design. PARTICIPANTS: We contacted 41 physicians through letters and emails and 10 agreed to participate, five were male and five female. DATA COLLECTION AND ANALYSIS: Ten interviews were recorded, transcribed verbatim and anonymised. The material was analysed inductively following a grounded theory approach with open coding using the software atlas.ti. RESULTS: Key themes that were identified were education and career path, understanding of medicine and medical profession, experiences with vaccines, doctor-patient interactions and continuous education activities and the link to VH. GPs and paediatricians' vaccine-hesitant attitudes developed during their medical training and, in particular, during extracurricular training in homeopathy, which most of the participants completed. Most participants work in private practices rather than with contracts with social insurance because they are not satisfied with the health system. Furthermore, they are critical of biomedicine. Most of the interview partners do not consider themselves antivaccination, but are sceptical towards vaccines and especially point out the side effects. Most do not vaccinate in their practices and some do only occasionally. Their vaccine-hesitant views are often fostered through respective online communities of vaccine-hesitant HCWs. CONCLUSIONS: More studies on a connection between complementary medicine and vaccine-hesitant views of HCWs are needed. Education about vaccines and infectious diseases among healthworkers must increase especially tailored towards the use of internet and social media. Physicians should be made aware that through time and empathy towards their patients they could have a positive impact on undecided patients and parents regarding vaccine decisions.

Is health literacy of adolescent athletes' parents whose children belonged to sports clubs related to their children's intention to receive medications, vaccines, supplements, and energy drinks? A cross-sectional study.

BACKGROUND: Adolescent athletes' values ​regarding health behaviors, including their attitudes toward doping, are largely derived from those of their parents. Therefore, clarifying the factors that affect parents' intentions regarding their children's medicine intake and nutrition can help elucidate the process of forming values ​​of healthy behaviors in young athletes. METHODS: Between March 8 and March 9, 2021, an online questionnaire survey was conducted via an Internet research company; data from 2,000 residents in Japan were collected. Participants were male and female residents aged 30-59 years with children in elementary or high school and belonging to sports clubs. The survey items included respondent's and child's basic information, respondent's health literacy, and level of sports in which the respondent and child were (or are) engaged. Respondents were also asked if they would like their children to receive prescription drugs, over-the-counter drugs, herbal medicines, vaccines, supplements, or energy drinks. Logistic regression analysis was performed to analyze the relationship between respondents' basic information and health literacy and their intention to receive prescription and over-the-counter drugs, herbal medicines, vaccines, supplements, and energy drinks. RESULTS: Higher parental health literacy was associated with higher children's willingness to receive prescription drugs (odds ratio [OR] = 1.025, 95% confidence interval [CI]: 1.016-1.035), over-the-counter drugs (OR = 1.012, 95% CI: 1.003-1.021), prescription herbal medicines (OR = 1.021, 95% CI: 1.021-1.030), over-the-counter herbal medicines (OR = 1.012, 95% CI: 1.003-1.021), and vaccines (OR = 1.025, 95% CI: 1.016-1.035). Conversely, the children's intention to receive energy drinks (OR = 0.990, 95% CI: 0.980-1.000) decreased significantly. As the child's athletic level increased, parents' willingness for their children to receive oral prescription medicines decreased (OR = 0.886, 95% CI: 0.791-0.992) and that to receive supplements (OR = 1.492, 95% CI: 1.330-1.673) and energy drinks significantly increased (OR = 1.480, 95% CI: 1.307-1.676). CONCLUSION: Health literacy of adolescent athletes' parents is associated with their children's willingness to receive medicines. Healthcare providers should counsel parents of adolescent athletes to allow their children to receive necessary drug treatments and prevent doping violations caused by supplement intake.

The effect of COVID-19 infection on patients with rheumatic diseases in China.

OBJECTIVES: At the end of 2022, the COVID-19 outbreak erupted in China, and BA.5.2 or BF.7 subtypes of Omicron novel variations were implicated in more than 90% of the cases. We created a real-world questionnaire survey to better understand how this new variant pandemic was affecting rheumatic patients in China. METHODS: During the COVID-19 outbreak in China, the subjects of this study were rheumatic patients and non-rheumatic individuals (control group), who were matched for sex and age. Professional physicians carefully questioned the participants before administering a questionnaire as part of the study. This study focused on the general baseline characteristics, clinical symptoms and treatment after COVID-19 infection, and the target populations' awareness of COVID-19. RESULTS: The study included 1130 participants, of whom 572 were assigned to the rheumatic group and 558 to the control group. The percentage of vaccinated controls was significantly higher than that of rheumatic patients (90.1% vs. 62.8%, p < 0.001), while the rate of COVID-19 infection was not significantly different between the two groups (82.3% vs. 86.6%, p = 0.051). Patients with rheumatic disease experienced substantially more days of fever following infection (2.87 ± 3.42 vs. 2.18 ± 1.65, p = 0.002) compared to individuals in the control group. The rheumatic patients had a greater prevalence of cough (67.1% vs. 54.0%, p < 0.001), somnipathy (13.8% vs. 6.0%, p < 0.001), and conjunctivitis/ophthalmodynia (5.3% vs. 2.1%, p = 0.008), while dry throat/throat pain/weakness (49.9% vs. 59.4%, p = 0.003), myalgia/osteodynia (33.3% vs. 41.8%, p = 0.003), and dyspnea (14.0% vs. 25.3%, p < 0.001) were more likely to occur in non-rheumatic group after infection. Human immunoglobulin (2.1% vs. 0.2%, p = 0.006), glucocorticoids (19.5% vs. 1.6%, p < 0.001), oxygen support (6.8% vs. 2.1%, p < 0.001), and traditional Chinese medicine (21.9% vs. 16.6%, p = 0.037) were all more frequently used by rheumatic patients with COVID-19 infection. People in the control group were more confused about whether to use masks in following social activities after contracting COVID-19 (14.7% vs. 7.6%, p = 0.001). In the control group, more individuals than patients with rheumatic disease (25.1% vs. 13.4%, p < 0.001) expressed an interest to receive the vaccine again. After being exposed to COVID-19, the majority of rheumatic patients (66.9%) reported no discernible change, only 29.1% reported a worsening of their symptoms, and the remaining 4% indicated an improvement. CONCLUSIONS: After the COVID-19 outbreak in China, the proportion of patients with rheumatic diseases infected with the virus was similar to that of normal individuals. But the clinical symptoms, follow-up treatment requirements, and awareness of the COVID-19 among rheumatic patients were distinct from those among non-rheumatic patients, necessitating the use of individualized diagnosis and treatment plans as well as health advice by medical professionals in clinical work. Key Points • Despite there were different comorbidities and vaccination rates, the rate of COVID-19 infection in patients with rheumatic disease was similar to that of normal individuals. • After COVID-19 infection, rheumatic patients and normal controls had different clinical symptoms and drug usage. • After being exposed to COVID-19, the majority of rheumatic patients felt no significant change in the primary disease, while the normal controls was more likely to accept a new vaccine injection and confused about whether to use masks in following social activities.

Exploring Hollow Mesoporous Silica Nanoparticles as a Nanocarrier in the Delivery of Foot-And-Mouth Disease Virus-like Particle Vaccines.

Virus-like particle (VLP) vaccine is considered to be the most promising candidate alternative to the traditional inactivated vaccine for foot-and-mouth disease (FMD). To elicit a desired immune response, hollow mesoporous silica nanoparticles (HMSNs) have been synthesized and utilized as a nanocarrier for FMD VLP vaccine delivery. The as-prepared HMSNs displayed a relatively small particle size (∼260 nm), large cavity (∼150 nm), and thin wall (∼55 nm). The inherent structural superiorities make them ideal nanocarriers for the FMD VLP vaccine, which exhibited good biocompatibility, great protein-loading capacity, high antibody-response level, and protective efficiency, even comparable to commercial adjuvant ISA 206. All the results suggested that HMSNs may be a valid nanocarrier in VLP-based vaccines.

Micronanoparticled risedronate exhibits potent vaccine adjuvant effects.

Micro/Nano-scale particles are widely used as vaccine adjuvants to enhance immune response and improve antigen stability. While aluminum salt is one of the most common adjuvants approved for human use, its immunostimulatory capacity is suboptimal. In this study, we modified risedronate, an immunostimulant and anti-osteoporotic drug, to create zinc salt particle-based risedronate (Zn-RS), also termed particulate risedronate. Compared to soluble risedronate, micronanoparticled Zn-RS adjuvant demonstrated increased recruitment of innate cells, enhanced antigen uptake locally, and a similar antigen depot effect as aluminum salt. Furthermore, Zn-RS adjuvant directly and quickly stimulated immune cells, accelerated the formulation of germinal centers in lymph nodes, and facilitated the rapid production of antibodies. Importantly, Zn-RS adjuvant exhibited superior performance in both young and aged mice, effectively protecting against respiratory diseases such as SARS-CoV-2 challenge. Consequently, particulate risedronate showed great potential as an immune-enhancing vaccine adjuvant, particularly beneficial for vaccines targeting the susceptible elderly.

Significance of Vitamin Supplementation in Reducing the Severity of COVID-19.

Coronavirus disease-19 (COVID-19), a serious pandemic due to the SARS-CoV-2 virus infection, caused significant lockdowns, healthcare shortages, and deaths worldwide. The infection leads to an uncontrolled systemic inflammatory response causing severe respiratory distress and multiple-organ failure. Quick development of several vaccines efficiently controlled the spread of COVID-19. However, the rise of various new subvariants of COVID-19 demonstrated some concerns over the efficacy of existing vaccines. Currently, better vaccines to control these variants are still under development as several new subvariants of COVID-19, such as omicron BA-4, BA-5, and BF-7 are still impacting the world. Few antiviral treatments have been shown to control COVID-19 symptoms. Further, control of COVID-19 symptoms has been explored with many natural and synthetic adjuvant compounds in hopes of treating the deadly and contagious disease. Vitamins have been shown to modulate the immune system, function as antioxidants, and reduce the inflammatory response. Recent studies have investigated the potential role of vitamins, specifically vitamins A, B, C, D, and E, in reducing the immune and inflammatory responses and severity of the complication. In this brief article, we discussed our current understanding of the role of vitamins in controlling COVID-19 symptoms and their potential use as adjuvant therapy.

Structural analysis of a soluble polysaccharide GSPA-0.3 from the root of Panax ginseng C. A. Meyer and its adjuvant activity with mechanism investigation.

A novel polysaccharide (GSPA-0.3) was isolated and purified from the root of cultivated Panax ginseng C. A. Meyer, and its structure, adjuvant activities, and mechanisms for inducing the maturation of mouse dendritic 2.4 cells (DC2.4) were extensively studied. Fraction GSPA-0.3, mainly composed by the galacturonic acid, galactose, arabinose, glucose, rhamnose, mannose, and xylose, had a molecular weight of 62,722 Da. The main chain of GSPA-0.3 was composed of →3)-α-L-Rhap-(1→, →4)-α-D-GalpA-(1→, and →3, 4)-α-D-GalpA-(1→. Branched chains comprised α-L-Araf-(1→3, 5)-α-L-Araf-(1→5)-α-L-Araf-(1→, α-D-Glcp-(1→6)-α-D-Glcp-(1→6)-α-D-Glcp-(1→, ß-D-Galp-(1→4)-ß-D-Galp-(1→4)-ß-D-Galp-(1→, and α-D-GalpA-(1→ units connected to the C3 position of →3, 4)-α-D-GalpA-(1→. In vivo, GSPA-0.3 was found to stimulate the production of IgG, IgG1, and IgG2a; increase the splenocyte proliferation index; and promote the expression of GATA-3, T-bet, IFN-γ, and IL-4 in H1N1 vaccine-immunized mice. Moreover, GSPA-0.3 significantly increased the levels of neutralizing antibodies in the mice, and its adjuvant activity was found to be superior to aluminum adjuvant (Alum adjuvant). Mechanistic investigations showed that GSPA-0.3 activated the TLR4-dependent pathway by upregulating the expressions of TLR4, MyD88, TRAF-6, and NF-κB proteins and gens. The results presented herein suggested that GSPA-0.3 could significantly promote the efficacy of the H1N1 vaccine by modulating Th1/Th2 response via the TLR4-MyD88-NF-κB signaling pathway.

Ordered mesoporous silicas for potential applications in solid vaccine formulations.

In an effort to develop efficient vaccine formulations, the use of ordered mesoporous silica (SBA-15) as an antigen carrier has been investigated. SBA-15 has required properties such as high surface area and pore volume, including narrow pore size distribution to protect antigens inside its matrix. This study aimed to examine the impact of solvent removal methods, specifically freeze-drying and evaporation on the intrinsic properties of an immunogenic complex. The immunogenic complexes, synthesized and incorporated with BSA, were characterized by various physicochemical techniques. Small Angle X-ray Scattering measurements revealed the characteristic reflections associated to pure SBA-15, indicating the preservation of the silica mesostructured following BSA incorporation and the formation of BSA aggregates within the macropore region. Nitrogen Adsorption Isotherm measurements demonstrated a decrease in surface area and pore volume for all samples, indicating that the BSA was incorporated into the SBA-15 matrix. Fluorescence spectroscopy evidenced that the tryptophan residues in BSA inside SBA-15 or in solution displayed similar spectra, showing the preservation of the aromatic residues' environment. The Circular Dichroism spectra of BSA in both conditions suggest the preservation of its native secondary structure after the encapsulation process. The immunogenic analysis with the detection of anti-BSA IgG did not give any significant difference between the non-dried, freeze-dried or evaporated groups. However, all groups containing BSA and SBA-15 showed results almost three times higher than the groups with pure BSA (control group). These facts indicate that none of the BSA incorporation methods interfered with the immunogenicity of the complex. In particular, the freeze-dried process is regularly used in the pharmaceutical industry, therefore its adequacy to produce immunogenic complexes was proved Furthermore, the results showed that SBA-15 increased the immunogenic activity of BSA.

Reconstituted dry powder formulations of ZnO-adjuvanted ovalbumin induce equivalent antigen specific antibodies but lower T cell responses than ovalbumin adjuvanted with Alhydrogel® or cationic adjuvant formulation 01 (CAF®01).

Most licensed human vaccines are based on liquid dosage forms but have poor storage stability and require continuous and expensive cold-chain storage. In contrast, the use of solid vaccine dosage forms produced by for example spray drying, extends shelf life and eliminates the need for a cold chain. Zinc oxide (ZnO)-based nanoparticles display immunomodulatory properties, but their adjuvant effect as a dry powder formulation is unknown. Here, we show that reconstituted dry powder formulations of ZnO particles containing the model antigen ovalbumin (OVA) induce antigen-specific CD8+ T-cell and humoral responses. By systematically varying the ratio between ZnO and mannitol during spray drying, we manufactured dry powder formulations of OVA-containing ZnO particles that displayed: (i) a spherical or wrinkled surface morphology, (ii) an aerodynamic diameter and particle size distribution optimal for deep lung deposition, and (iii) aerosolization properties suitable for lung delivery. Reconstituted dry powder formulations of ZnO particles were well-tolerated by Calu-3 lung epithelial cells. Furthermore, almost equivalent OVA-specific serum antibody responses were stimulated by reconstituted ZnO particles, OVA adjuvanted with Alhydrogel®, and OVA adjuvanted with the cationic adjuvant formulation 01 (CAF®01). However, reconstituted dry powder ZnO particles and OVA adjuvanted with Alhydrogel® induced significantly lower OVA-specific CD8+CD44+ T-cell responses in the spleen than OVA adjuvanted with CAF®01. Similarly, reconstituted dry powder ZnO particles activated significantly lower percentages of follicular helper T cells and germinal center B cells in the draining lymph nodes than OVA adjuvanted with CAF®01. Overall, our results show that reconstituted dry powder formulations of ZnO nanoparticles can induce antigen-specific antibodies and can be used in vaccines to enhance antigen-specific humoral immune responses against subunit protein antigens.

Understanding and explaining the link between anthroposophy and vaccine hesitancy: a systematic review.

BACKGROUND: Due to low vaccination uptake and measles outbreaks across Europe, public health authorities have paid increasing attention to anthroposophic communities. Public media outlets have further described these communities as vaccine refusers or "anti-vaxxers". The aim of this review was to understand the scope of the problem and explore assumptions about vaccination beliefs in anthroposophic communities. For the purpose of this review, we define anthroposophic communities as people following some/certain views more or less loosely connected to the philosophies of anthroposophy. The systematic review addresses three research questions and (1) collates evidence documenting outbreaks linked to anthroposophic communities, (2) literature on vaccination coverage in anthroposophic communities, and (3) lastly describes literature that summarizes theories and factors influencing vaccine decision-making in anthroposophic communities. METHODS: This is a systematic review using the following databases: Medline, Web of Science, Psycinfo, and CINAHL. Double-blinded article screening was conducted by two researchers. Data was summarized to address the research questions. For the qualitative research question the data was analysed using thematic analysis with the assistance of Nvivo12.0. RESULTS: There were 12 articles documenting 18 measles outbreaks linked to anthroposophic communities between the years 2000 and 2012. Seven articles describe lower vaccination uptake in anthroposophic communities than in other communities, although one article describes that vaccination coverage in low-income communities with a migrant background was lower than in the anthroposophic community they studied. We found eight articles examining factors and theories influencing vaccine decision making in anthroposophic communities. The qualitative analysis revealed four common themes. Firstly, there was a very broad spectrum of vaccine beliefs among the anthroposophic communities. Secondly, there was a consistent narrative about problems or concerns with vaccines, including toxicity and lack of trust in the system. Thirdly, there was a strong notion of the importance of making individual and well-informed choices as opposed to simply following the masses. Lastly, making vaccine choices different from public health guidelines was highly stigmatized by those outside of the anthroposophic community but also those within the community. CONCLUSION: Continuing to further knowledge of vaccine beliefs in anthroposophic communities is particularly important in view of increasing measles rates and potential sudden reliance on vaccines for emerging diseases. However, popular assumptions about vaccine beliefs in anthroposophic communities are challenged by the data presented in this systematic review.

Bifidobacterium infantis supplementation versus placebo in early life to improve immunity in infants exposed to HIV: a protocol for a randomized trial.

INTRODUCTION: Infants who are born from mothers with HIV (infants who are HIV exposed but uninfected; iHEU) are at higher risk of morbidity and display multiple immune alterations compared to infants who are HIV-unexposed (iHU). Easily implementable strategies to improve immunity of iHEU, and possibly subsequent clinical health outcomes, are needed. iHEU have altered gut microbiome composition and bifidobacterial depletion, and relative abundance of Bifidobacterium infantis has been associated with immune ontogeny, including humoral and cellular vaccine responses. Therefore, we will assess microbiological and immunological phenotypes and clinical outcomes in a randomized, double-blinded trial of B. infantis Rosell®-33 versus placebo given during the first month of life in South African iHEU. METHODS: This is a parallel, randomised, controlled trial. Two-hundred breastfed iHEU will be enrolled from the Khayelitsha Site B Midwife Obstetric Unit in Cape Town, South Africa and 1:1 randomised to receive 8 × 109 CFU B. infantis Rosell®-33 daily or placebo for the first 4 weeks of life, starting on day 1-3 of life. Infants will be followed over 36 weeks with extensive collection of meta-data and samples. Primary outcomes include gut microbiome composition and diversity, intestinal inflammation and microbial translocation and cellular vaccine responses. Additional outcomes include biological (e.g. gut metabolome and T cell phenotypes) and clinical (e.g. growth and morbidity) outcome measures. DISCUSSION: The results of this trial will provide evidence whether B. infantis supplementation during early life could improve health outcomes for iHEU. ETHICS AND DISSEMINATION: Approval for this study has been obtained from the ethics committees at the University of Cape Town (HREC Ref 697/2022) and Seattle Children's Research Institute (STUDY00003679). TRIAL REGISTRATION: Pan African Clinical Trials Registry Identifier: PACTR202301748714019. TRIALS: gov: NCT05923333. PROTOCOL VERSION: Version 1.8, dated 18 July 2023.

Manganese-Based Nanoparticle Vaccine for Combating Fatal Bacterial Pneumonia.

Bacterial pneumonia is the leading cause of death worldwide among all infectious diseases. However, currently available vaccines against fatal bacterial lung infections, e.g., pneumonic plague, are accompanied by limitations, including insufficient antigen-adjuvant co-delivery and inadequate immune stimulation. Therefore, there is an urgent requirement to develop next-generation vaccines to improve the interaction between antigen and adjuvant, as well as enhance the effects of immune stimulation. This study develops a novel amino-decorated mesoporous manganese silicate nanoparticle (AMMSN) loaded with rF1-V10 (rF1-V10@AMMSN) to prevent pneumonic plague. These results suggest that subcutaneous immunization with rF1-V10@AMMSN in a prime-boost strategy induces robust production of rF1-V10-specific IgG antibodies with a geometric mean titer of 315,844 at day 42 post-primary immunization, which confers complete protection to mice against 50 × LD50 of Yersinia pestis (Y. pestis) challenge via the aerosolized intratracheal route. Mechanistically, rF1-V10@AMMSN can be taken up by dendritic cells (DCs) and promote DCs maturation through activation of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway and production of type I interferon. This process results in enhanced antigen presentation and promotes rF1-V10-mediated protection against Y. pestis infection. This manganese-based nanoparticle vaccine represents a valuable strategy for combating fatal bacterial pneumonia.

Efficacy and feasibility of SMS m-Health for the detection of adverse events following immunisation (AEFIs) in resource-limited setting-The Zimbabwe stimulated telephone assisted rapid safety surveillance (Zm-STARSS) randomised control trial.

INTRODUCTION: The mHealth active participant centred (MAPC) adverse events following immunisation (AEFI) surveillance is a promising area for early AEFI detection resulting in risk minimisation. Passive (spontaneous) AEFI surveillance is the backbone for vaccine pharmacovigilance, but has inherent drawbacks of under reporting, and requires strengthening with active surveillance methods. AIM: The Zimbabwe stimulated telephone assisted rapid safety surveillance (Zm-STARSS) randomised controlled trial (RCT) sought to evaluate the efficacy and feasibility of AEFI detection using a short message service (SMS) and computer assisted telephone interview (CATI) approach. METHOD: A multicentre Zm-STARSS RCT enrolled consented adult vaccinees or parents or guardians of children receiving vaccines, including COVID-19 vaccines, at study vaccination clinics. At enrolment study participants were randomised to either SMS-CATI group or control group. SMS prompts were sent on days 0-2 and 14 post-vaccination to SMS-CATI group to ascertain if a medically attendance or attention due to an Adverse event following immunisation (AEFI) had occurred. However, no SMSs were sent to the control group. SMS-CATI group who responded "Yes" to SMS prompts were interviewed by research healthcare workers (RHCWs) who completed a CATI to determine if an AEFI had occurred whilst an AEFI in control group was determined from passive AEFI reporting channels. The primary study outcome was the AEFI detection rate in the SMS-CATI group compared to the control group. RESULTS: A total of 4560 participants were enrolled after signed informed consent, all were encouraged to report AEFIs and randomised automatically on 1:1 basis into two arms SMS CATI intervention group (n = 2280) and a control passive AEFI surveillance group (n = 2280) on day 0. A total of 704 (31 %) participants responded to the SMS prompts, with 75 % (528/704) indicating "No" and 25 % (176/704) reporting "Yes" to seeking medical attention or attendance post-immunisation. 69 % (121/176) completed a CATI survey but in only 36 % (44/121) was the AEFI confirmed. There were no AEFIs reported in control group participants. The detection rate of a AEFI associated with medically attendance or attention using the SMS-CATI methodology was 2 % (44/2280) on an intention to treat cohort. CONCLUSION: Despite the low SMS response and CATI completion rate, we demonstrated that Zm-STARSS SMS system improves AEFI detection compared to passive AEFI surveillance. We recommend that this and similar approaches are explored further using cost-effective multi-channel digital approaches for holistic pharmacovigilance to improve AEFI detection in Low Middle-Income Countries (LMICs) for all vaccines.