Transcutaneous Immunization of 1D Rod-Like Tobacco-Mosaic-Virus-Based Peptide Vaccine via Tip-Loaded Dissolving Microneedles.

Peptide vaccines induce specific neutralizing antibodies and are effective in disease prevention and treatment. However, peptide antigens have a low immunogenicity and are unstable, requiring efficient vaccine carriers to enhance their immunogenicity. Here, we develop a tobacco mosaic virus (TMV)-based peptide vaccine for transdermal immunization using a tip-loaded dissolving microneedle (MN) patch. TMV is decorated with the model peptide antigen PEP3. The prepared TMV-PEP3 promotes dendritic cell maturation and induces dendritic cells to overexpress MHC II, costimulatory factors, and pro-inflammatory factors. By encapsulation of TMV-PEP3 in the tips of a trehalose MN, TMV-PEP3 can be delivered by MN and significantly promote local immune cell infiltration. In vivo studies show that both subcutaneous injection and MN administration of TMV-PEP3 increase the production of anti-PEP3 IgG antibodies and the harvested serum can induce complement-dependent cytotoxicity. This work provides a promising strategy for constructing efficient and health-care-friendly peptide vaccines.

Low-dose oral food challenges.

BACKGROUND: Infants aged <1 year with confirmed food allergies generally need to avoid causative foods completely for a certain period. Low-dose oral food challenges (LD-OFCs) may be an effective strategy for safely introducing small amounts of causative foods to individuals with food allergies. This study clarified the safety of LD-OFCs in infants aged <1 year with food allergies. METHODS: We retrospectively analyzed the clinical records of LD-OFCs performed in infants aged <1 year allergic to hen's egg, cow's milk, or wheat between April 2014 and October 2017. Approximately 1/25th-1/20th of the egg white from a heated whole hen's egg, 3 mL heated cow's milk, and 2 g wheat noodles (udon) were used as challenge foods. We examined the LD-OFC results, including the induced symptoms and treatment required for positive LD-OFC results. RESULTS: The LD-Egg, LD-Milk, and LD-Wheat OFC groups comprised 68, 42, and 13 participants, respectively. The positivity rates for the LD-Egg, LD-Milk, and LD-Wheat OFC groups were 7%, 24%, and 0%, respectively. Patients predominantly exhibited skin symptoms, and most were treated with oral antihistamines alone. None of the patients experienced anaphylaxis or required adrenaline injections. CONCLUSIONS: Infants aged <1 year with food allergies can safely undergo LD-OFCs by consuming low doses of causative foods. Avoiding the complete elimination of causative foods is an important strategy for managing infants with food allergies when initially introducing causative foods.

An evaluation of the surveillance system for monitoring and reporting adverse events following immunization in Kebbi State, Northern Nigeria: a mixed method approach.

INTRODUCTION: Despite the benefits of periodic evaluation of the vaccine safety surveillance system, no formal assessment, to our knowledge, has been conducted in Nigeria. Hence, this study evaluated the surveillance system for adverse events following immunization (AEFI) to ascertain the system's functionality to inform vaccine safety considerations and guide communication strategies for demand generation. MATERIALS AND METHODS: The study employed a mixed-method approach. Survey questionnaires were administered to 274 routine immunization service providers in Kebbi State, Northern Nigeria, and data were analyzed descriptively using SPSS. In this study, 10 Key Informant Interviews and two Focus Group Discussions were conducted with senior officers and managers at sub-national and national levels within the immunization and surveillance landscape in Nigeria. The interview recordings were cleaned minimally, transcribed, and manually analyzed thematically. Finally, methodological triangulation was done to improve research rigor and provide a better understanding of the phenomena under investigation. RESULTS: Of the respondents, 201(73.4%) reported that the surveillance system can inform vaccine safety considerations while 170(62%) reported that the AEFI surveillance system can determine the magnitude of AEFI within the population. Further, 173(63%) reported that the surveillance system can provide timely feedback about causality assessment. However, 158(58%) of the respondents stated that the surveillance system is competent in informing communication strategies to improve immunization demand. Triangulation was done which showed dissonance in AEFI surveillance and vaccine safety considerations but partial agreement in immunization demand generation. Further, AEFI surveillance system attributes' triangulation revealed agreements (convergence) on simplicity and timeliness; partial agreements on acceptability, data quality, sensitivity, flexibility, and completeness; dissonance on representativeness and silence on stability, indicating a sub-optimal performance of the AEFI surveillance system in the study setting. Finally, the study unearthed some underlying health system factors impeding the AEFI surveillance system from fully fulfilling its objectives. CONCLUSION: The AEFI surveillance system in Northern Nigeria is well established but functioning sub-optimally. Based on the study findings, the capacity to provide information on vaccine safety exists but it is not robust enough to generate sufficient and convincing vaccine safety data and guide communication strategies for vaccine demand generation, especially for new vaccines and those under emergency authorization use.

Development of novel canine phage display-derived neutralizing monoclonal antibody fragments against rabies virus from immunized dogs.

Animal rabies is a potentially fatal infectious disease in mammals, especially dogs. Currently, the number of rabies cases in pet dogs is increasing in several regions of Thailand. However, no passive postexposure prophylaxis (PEP) has been developed to combat rabies infection in animals. As monoclonal antibodies (MAbs) are promising biological therapies for postinfection, we developed a canine-neutralizing MAb against rabies virus (RABV) via the single-chain variable fragment (scFv) platform. Immunized phage-displaying scFv libraries were constructed from PBMCs via the pComb3XSS system. Diverse canine VHVLκ and VHVLλ libraries containing 2.4 × 108 and 1.3 × 106 clones, respectively, were constructed. Five unique clones that show binding affinity with the RABV glycoprotein were then selected, of which K9RABVscFv1 and K9RABVscFv16 showed rapid fluorescent foci inhibition test (RFFIT) neutralizing titers above the human protective level of 0.5 IU/ml. Finally, in silico docking predictions revealed that the residues on the CDRs of these neutralizing clones interact mainly with similar antigenic sites II and III on the RABV glycoprotein. These candidates may be used to develop complete anti-RABV MAbs as a novel PEP protocol in pet dogs and other animals.

COVID-19 in Relation to Polypharmacy and Immunization (2020-2024).

BACKGROUND: Observational studies reported worse COVID-19 evolution in relation to polypharmacy and reductions in COVID-19 hospital admissions and death in patients receiving chronic antihistamine treatment. The current profile of hospitalized patients with regard to different variants was analyzed to identify specific targets for future prospective trials. METHODS: COVID-19 admissions to the Hospital of Terrassa (11 March 2020-28 August 2024 (n = 1457), from the integral Consorci Sanitari de Terrassa population (n = 167,386 people) were studied. Age, gender, the number of chronic treatments (nT), and immunization status were analyzed. RESULTS: After 5 May 2023, 291 patients (54% females) required COVID hospitalization. Of these, 39% received >8 nT (23% receiving 5-7 nT), 70.2% were >70 years, and 93.4% survived. In total, 12% of patients admitted after 5 May 2024 were not vaccinated, while 59% received ≥4 vaccines (43% within the last 12 months). In total, 49% of admitted patients presented no previous infection (while 3% presented infection during the last year). Delta or Omicron variants would have accounted for ≥80% of admissions > 60 years compared to the first pandemic wave if no vaccines existed. CONCLUSIONS: Patients > 70 years who receive ≥5 nT, without prior COVID-19 infections, should be the priority for prevention, with updated vaccination and early treatments to reduce hospitalizations.

The promise, progress, and challenges of in situ immunization agents in cancer immunotherapy.

In situ immunization (ISI) agents are an emerging and diverse class of locally acting cancer immunotherapeutic agents designed to promote innate immune activation in the early steps of the cancer immunity cycle to ultimately support development of a systemic tumor-specific immune response and protective immunologic memory. The aims of this review are to: (i) provide an introduction to ISI; (ii) summarize the history of ISI agents; (iii) expound upon the mechanism(s) and therapeutic objective(s) of ISI; (iv) compare the various approaches and therapeutic modalities developed and investigated to date; and (v) summarize clinical experiences in an effort to highlight the utility as well as the lessons and challenges of this promising approach. A prospective roadmap for future clinical development is provided that focuses on early and late-stage trial design considerations, the rationale and importance of investigating combination treatment, and the prospective use of ISI agents in the neoadjuvant setting.

Loss of HIV candidate vaccine efficacy in male macaques by mucosal nanoparticle immunization rescued by V2-specific response.

Systemic vaccination of macaques with V1-deleted (ΔV1) envelope immunogens reduce the risk of SIVmac251 acquisition by approximately 60%, with protective roles played by V2-specific ADCC and envelope-specific mucosal IL-17+NKp44+ innate lymphoid cells (ILCs). We investigated whether increased mucosal responses to V2 benefit vaccine efficacy by delivering oral nanoparticles (NPs) that release V2-scaffolded on Typhoid Toxin B (TTB) to the large intestine. Strikingly, mucosal immunization of male macaques abrogated vaccine efficacy with control TTB or empty NPs, but vaccine efficacy of up to 47.6% was preserved with V2-TTB NPs. The deleterious effects of NPs were linked to preferential recruitment of mucosal plasmacytoid dendritic cells (pDCs), reduction of protective mucosal NKp44+ ILCs, increased non-protective mucosal PMA/Ionomycin-induced IFN-γ+NKG2A-NKp44-ILCs, and increased levels of mucosal activated Ki67+CD4+ T cells, a potential target for virus infection. V2-TTB NP mucosal boosting rescued vaccine efficacy, likely via high avidity V2-specific antibodies mediating ADCC, and higher frequencies of mucosal NKp44+ ILCs and of ∆V1gp120 binding antibody-secreting B cells in the rectal mucosa. These findings emphasize the central role of systemic immunization and mucosal V2-specific antibodies in the protection afforded by ΔV1 envelope immunogens and encourage careful evaluation of vaccine delivery platforms to avoid inducing immune responses favorable to HIV transmission.

Facilitators and barriers to maternal immunization and strategies to improve uptake in low-income and lower-middle income countries: A systematic review.

Maternal immunization (MI) is an emerging strategy to combat infant mortality in low-income (LIC) and lower-middle income countries (LMIC). We conducted a systematic review to identify the facilitators and barriers to MI and strategies that improve uptake in LICs and LMICs. We searched PubMed, Cochrane Library, and Scopus for quantitative, qualitative, and mixed-methods studies published in English from January 1, 2011, to October 31, 2021, from all LICs and LMICs. Data was appraised using the Mixed Methods Appraisal Tool. 55 studies were included. The major barriers were low knowledge and concern of vaccine safety among pregnant women and healthcare providers (HCP). HCP's recommendation, maternal knowledge, vaccine confidence and ≥4 antenatal care (ANC) visits facilitated uptake. The key strategies encompassed health financing, reminders, intersectoral coordination, integration, community engagement, capacity building, and education. Community-based delivery models were effective. Tailored programs are needed to improve ANC access, and educate pregnant women and HCPs.

Protection of Rabbits Against Colonization and Morbidity Associated With Toxigenic Pasteurella multocida by Immunization With Inactivated Heat-labile Toxin.

BACKGROUND/AIM: Pasteurella multocida is a significant cause of morbidity and mortality in rabbits, as well as other species. Some isolates elaborate a heat-labile toxin (PMT) that has been shown to be an important virulence factor. Though previous studies have demonstrated protective immunity can be conferred via immunization of rabbits with heat-inactivated PMT (IPMT), we investigated the ability of immunization to impact colonization of P. multocida. MATERIALS AND METHODS: Rabbits were immunized at days 0, 7 and 14 with either phosphate buffered saline (PBS), the mucosal adjuvant cholera toxin (CT), IMPT or IPMT + CT. Male New Zealand white rabbits were used and confirmed to be free of P. multocida prior to experimentation. RESULTS: Serum IgG and nasal lavage fluid IgA responses directed against PMT were found in rabbits immunized with IPMT, with or without CT, but not in those immunized with only PBS or CT; and the addition of CT to IPMT enhanced the response. Significantly more P. multocida CFUs (p≤0.05) were cultured from the lungs of rabbits immunized with IPMT, with or without CT, compared to those administered only PBS or CT, although no differences were observed in nasal lavage fluid samples. Further, immunization IPMT, with or without CT, conferred protection against pleuritis and pneumonia. CONCLUSION: PMT, in addition to its role as a virulence factor, may serve as a colonization factor for P. multocida in the lungs of rabbits.

Immunization with recombinant Streptococcus pneumoniae PgdA protects mice against lung invasion.

Current pneumococcal vaccines, including the pneumococcal polysaccharide (PPV23) and conjugate (PCV13) vaccines, offer protection against specific serotypes but pose risks of serotype replacement that can alter the composition of the nasopharyngeal microbiota. To address this challenge, a novel strategy has been proposed to provide effective protection without disrupting the colonization of other bacterial populations. In our study, we found that subcutaneous immunization with recombinant peptidoglycan N-acetylglucosamine deacetylase A (rPgdA) elicited robust humoral and cellular immune responses, significantly reducing the invasion of Streptococcus pneumoniae in the lungs without affecting nasopharyngeal carriage. Furthermore, rPgdA antisera were shown to diminish bacterial invasion of lung epithelial cells in vitro. Notably, sera from patients with invasive pneumococcal infections exhibited higher levels of antibodies against the PgdA protein compared to sera from healthy adults, suggesting that a natural immune response to this protein occurs during infection. These results suggest a promising new target for the development of pneumococcal vaccines.

Surveillance for adverse events following immunization in Hebei Province, China, 2018-2020.

The aim of this study was to analyze the incidence and characteristics of adverse events following immunization (AEFI) with post-licensure vaccines used in Hebei province from 2018 to 2020 and to evaluate the safety of vaccines. All information of AEFI was gained from national adverse event following immunization surveillance system (NAEFISS) in Hebei Province from 2018 to 2020. Descriptive epidemiology method was used to analyze the data about AEFI in Hebei province. Reporting rates of AEFI were calculated by sex, age, city, categories of AEFI, severity of AEFI, reaction categories, etc. A total of 35,999 AEFI were reported through NAEFISS, and the average annual rate was 47.64/100,000 doses. The reporting rates of common adverse reactions and rare adverse reactions were 46.37/100,000 doses and 1.05/100,000 doses. The male-to-female ratio was 1.26:1. Most of the AEFI were concentrated in the ≤1 year age group and were reported in the second quarter and third quarter. The majority of AEFI were reported to be recovered or improved, and about 62% of the AEFI occurred within 24 hours after vaccination. Vaccines associated with the highest reporting rate of AEFI were diphtheria, tetanus and acellular pertussis combined vaccine (DTaP, 170.45/100,000 doses). The reporting rate of allergic rash was found to be the highest in the adverse reactions (0.29/100,000 doses). The majority of AEFI cases were common adverse reactions, while serious rare adverse reactions caused by vaccines were extremely uncommon, and all vaccines used in Hebei Province were safe.

Identifying the zero-dose and under-immunized children in Bangladesh: Approaches and experiences.

This paper presents and elaborates on empirical methods and approaches used to identify Zero-Dose (ZD) and Under-immunized (UI) children as well as the communities that these children reside in within Bangladesh. This paper also describes demand- and supply side-barriers that lead to children being ZD and UI in the country. Time period for the study was December 2022-May 2023. The study methodology encompassed secondary data analysis using data from national surveys, primary data collection and analysis via a lot quality assurance sampling (LQAS) survey and also, qualitative data collection and analysis. Study population included caregivers of children aged 4.5 months (4 months 15 days) to 23 months for the LQAS survey. The qualitative component included policymakers, program managers and service providers working in immunization as well as mothers in the selected study areas who had a living child aged less than 2 years as the study population. Our data analysis confirms existence of ZD and UI children in areas which were categorized into haor (wetlands), hilly, char (sandy/silty land surrounded by water), coastal, plain land and urban slums. Determinant analysis showed that the mother's level of education, antenatal visits made, and access to media were significantly associated with children being ZD or UI. Reproductive autonomy emerged as a key factor that had prominent impact on a child being ZD. The qualitative analysis indicated the importance of population migration, health workforce shortages and lack of access to transportation as prominent barriers to immunization. Notably, the methods and approaches used in this study are both effective and easily replicable to identify ZD and UI children. The drivers of ZD and UI along with the barriers to immunization provide potential areas for intervention by policy-makers and can apprise about interventions to be tested in future implementation research.

Enhanced Effect of ß-Lactoglobulin Immunization in Mice with Mild Intestinal Deterioration Caused by Low-Dose Dextran Sulphate Sodium: A New Experimental Approach to Allergy Studies.

BACKGROUND/OBJECTIVES: Cow's milk allergy is one of the most common food allergies in children, and its pathomechanism is still under investigation. Recently, an increasing number of studies have linked food allergy to intestinal barrier dysfunction. The present study aimed to investigate changes in the intestinal microenvironment during the development of ß-lactoglobulin (ß-lg) allergy under conditions of early intestinal dysfunction. METHODS: BALB/c mice received intraperitoneal ß-lg with Freund's adjuvant, followed by oral ß-lg while receiving dextran sulphate sodium salt (DSS) in their drinking water (0.2% w/v). The immunized group without DSS and the groups receiving saline, oral ß-lg, or DSS served as controls. RESULTS: The study showed that the immunization effect was greater in mice with mild intestinal barrier dysfunction. Although DSS did not affect the mice's humoral response to ß-lg, in combination with ß-lg, it significantly altered their cellular response, affecting the induction and distribution of T cells in the inductive and peripheral tissues and the activation of immune mediators. Administration of ß-lg to sensitized mice receiving DSS increased disease activity index (DAI) scores and pro-inflammatory cytokine activity, altered the distribution of claudins and zonulin 1 (ZO-1) in the colonic tissue, and negatively affected the balance and activity of the gut microbiota. CONCLUSIONS: The research model used appears attractive for studying food allergen sensitization, particularly in relation to the initial events leading to mucosal inflammation and the development of food hypersensitivity.

Systemic immunostimulation induces glucocorticoid-mediated thymic involution succeeded by rebound hyperplasia which is impaired in aged recipients.

The thymus is the central organ involved with T-cell development and the production of naïve T cells. During normal aging, the thymus undergoes marked involution, reducing naïve T-cell output and resulting in a predominance of long-lived memory T cells in the periphery. Outside of aging, systemic stress responses that induce corticosteroids (CS), or other insults such as radiation exposure, induce thymocyte apoptosis, resulting in a transient acute thymic involution with subsequent recovery occurring after cessation of the stimulus. Despite the increasing utilization of immunostimulatory regimens in cancer, effects on the thymus and naïve T cell output have not been well characterized. Using both mouse and human systems, the thymic effects of systemic immunostimulatory regimens, such as high dose IL-2 (HD IL-2) with or without agonistic anti-CD40 mAbs and acute primary viral infection, were investigated. These regimens produced a marked acute thymic involution in mice, which correlated with elevated serum glucocorticoid levels and a diminishment of naïve T cells in the periphery. This effect was transient and followed with a rapid thymic "rebound" effect, in which an even greater quantity of thymocytes was observed compared to controls. Similar results were observed in humans, as patients receiving HD IL-2 treatment for cancer demonstrated significantly increased cortisol levels, accompanied by decreased peripheral blood naïve T cells and reduced T-cell receptor excision circles (TRECs), a marker indicative of recent thymic emigrants. Mice adrenalectomized prior to receiving immunotherapy or viral infection demonstrated protection from this glucocorticoid-mediated thymic involution, despite experiencing a substantially higher inflammatory cytokine response and increased immunopathology. Investigation into the effects of immunostimulation on middle aged (7-12 months) and advance aged (22-24 months) mice, which had already undergone significant thymic involution and had a diminished naïve T cell population in the periphery at baseline, revealed that even further involution was incurred. Thymic rebound hyperplasia, however, only occurred in young and middle-aged recipients, while advance aged not only lacked this rebound hyperplasia, but were entirely absent of any indication of thymic restoration. This coincided with prolonged deficits in naïve T cell numbers in advanced aged recipients, further skewing the already memory dominant T cell pool. These results demonstrate that, in both mice and humans, systemic immunostimulatory cancer therapies, as well as immune challenges like subacute viral infections, have the potential to induce profound, but transient, glucocorticoid-mediated thymic involution and substantially reduced thymic output, resulting in the reduction of peripheral naive T cells. This can then be followed by a marked rebound effect with naïve T cell restoration, events that were shown not to occur in advanced-aged mice.

Multilevel and geographically weighted regression analysis of factors associated with full immunization among children aged 12-23 months in Ethiopia.

Immunization is the process of building immunity or resistance to an infectious disease, typically through administering a vaccine. It is one of the most effective strategies for lowering child morbidity and death. It protects against more than 20 potentially fatal diseases, increasing longevity and health. Despite progress, Ethiopia failed to meet its vaccination coverage target. The magnitude of full immunization is different across areas. Therefore, conducting geographically weighted regression to identify the local factors and multilevel analysis to investigate and identify factors associated with full immunization coverage among children aged 12-23 months is necessary. The study was conducted using the 2019 Ethiopian Mini Demographic Health Survey dataset. A sample of 1028 weighted children aged 12-23 months were included in the analysis. Descriptive statistics were used to describe variables. For the spatial analysis, Arc-GIS version 10.8 statistical software was used. Spatial regression (geographically weighted regression) was done to identify factors associated with the proportion of full immunization, and model comparison was based on adjusted R2 and Akaike Information Criteria (AICc). Multilevel mixed-effect binary logistic regression models were fitted to identify factors associated with full immunization. The fitted models were compared based on log-likelihood, deviance, median odds ratio, and Proportional Change in Variance. Finally, statistically significant factors were reported using an adjusted odd ratio (AOR) with a 95% Confidence Interval for fixed effect. All variables with a p-value less than 0.05 in the final model were considered statistically significant factors. In Ethiopia, the overall full immunization coverage among children aged 12-23 months was 40.58%, with spatial variation across regions in Ethiopia. The significant spatial distribution of full immunization coverage among children aged 12-23 months was detected in northern Tigray, Addis Ababa, central Oromia, and southeastern Amhara regions. The proportion of rural residents,the proportion of women aged 35-44 years,  the proportion of women who had ANC 4 and above andthe proportion of women who had PNC were local factors associated with the proportion of full immunization among children aged 12-23 months. Rural residence [AOR 0.27 (95% CI 0.10, 0.70)], family size 4 and above[AOR 0.41 (95% CI 0.17, 0.96)], never breastfeed [AOR 0.026(95% CI 0.003, 0.21)], 1-3 times ANC visit [AOR 0.45 (95% CI 0.23, 0.86)], being from Oromia region [AOR 0.23 (95% CI 0.05, 0.97)], Eastern pastoralist region [AOR 0.09 (95% CI 0.023, 0.35)], age 35-44 years [(AOR 6 (95% CI 1.57, 22.9)], and PNC [AOR 2.40 (95% CI 1.24, 4.8)] were significant factors associated with fully immunization in multilevel mixed effect analysis. Full immunization coverage in Ethiopia is below the global target with significant geographical variation. The high proportion of rural residents, the high proportion of women who had ANC 4 and above, mothers who had a high proportion of PNC, and the high proportion women age 35-44 years were local geographical factors for the proportion of full immunization among children age 12-23 months in Ethiopia. Women who had PNC, ANC visits four or more times, and increased maternal age were positively associated, whereas larger family size, no breastfeeding, rural residence, and being from Oromia and eastern pastoralist region were negatively associated with full immunization. Strengthening maternal and child health services, focusing on rural areas and low-coverage regions, is essential to increase immunization coverage in Ethiopia.

Immunization of cows with HIV envelope trimers generates broadly neutralizing antibodies to the V2-apex from the ultralong CDRH3 repertoire.

The generation of broadly neutralizing antibodies (bnAbs) to conserved epitopes on HIV Envelope (Env) is one of the cornerstones of HIV vaccine research. The animal models commonly used for HIV do not reliably produce a potent broadly neutralizing serum antibody response, with the exception of cows. Cows have previously produced a CD4 binding site response by homologous prime and boosting with a native-like Env trimer. In small animal models, other engineered immunogens were shown to focus antibody responses to the bnAb V2-apex region of Env. Here, we immunized two groups of cows (n = 4) with two regimens of V2-apex focusing Env immunogens to investigate whether antibody responses could be generated to the V2-apex on Env. Group 1 was immunized with chimpanzee simian immunodeficiency virus (SIV)-Env trimer that shares its V2-apex with HIV, followed by immunization with C108, a V2-apex focusing immunogen, and finally boosted with a cross-clade native-like trimer cocktail. Group 2 was immunized with HIV C108 Env trimer followed by the same HIV trimer cocktail as Group 1. Longitudinal serum analysis showed that one cow in each group developed serum neutralizing antibody responses to the V2-apex. Eight and 11 bnAbs were isolated from Group 1 and Group 2 cows, respectively, and showed moderate breadth and potency. Potent and broad responses in this study developed much later than previous cow immunizations that elicited CD4bs bnAbs responses and required several different immunogens. All isolated bnAbs were derived from the ultralong CDRH3 repertoire. The finding that cow antibodies can target more than one broadly neutralizing epitope on the HIV surface reveals the generality of elongated structures for the recognition of highly glycosylated proteins. The exclusive isolation of ultralong CDRH3 bnAbs, despite only comprising a small percent of the cow repertoire, suggests these antibodies outcompete the long and short CDRH3 antibodies during the bnAb response.

Generation of antigen-specific memory CD4 T cells by heterologous immunization enhances the magnitude of the germinal center response upon influenza infection.

Current influenza vaccine strategies have yet to overcome significant obstacles, including rapid antigenic drift of seasonal influenza viruses, in generating efficacious long-term humoral immunity. Due to the necessity of germinal center formation in generating long-lived high affinity antibodies, the germinal center has increasingly become a target for the development of novel or improvement of less-efficacious vaccines. However, there remains a major gap in current influenza research to effectively target T follicular helper cells during vaccination to alter the germinal center reaction. In this study, we used a heterologous infection or immunization priming strategy to seed an antigen-specific memory CD4+ T cell pool prior to influenza infection in mice to evaluate the effect of recalled memory T follicular helper cells in increased help to influenza-specific primary B cells and enhanced generation of neutralizing antibodies. We found that heterologous priming with intranasal infection with acute lymphocytic choriomeningitis virus (LCMV) or intramuscular immunization with adjuvanted recombinant LCMV glycoprotein induced increased antigen-specific effector CD4+ T and B cellular responses following infection with a recombinant influenza strain that expresses LCMV glycoprotein. Heterologously primed mice had increased expansion of secondary Th1 and Tfh cell subsets, including increased CD4+ TRM cells in the lung. However, the early enhancement of the germinal center cellular response following influenza infection did not impact influenza-specific antibody generation or B cell repertoires compared to primary influenza infection. Overall, our study suggests that while heterologous infection or immunization priming of CD4+ T cells is able to enhance the early germinal center reaction, further studies to understand how to target the germinal center and CD4+ T cells specifically to increase long-lived antiviral humoral immunity are needed.

A naturaly attenuated largemouth bass ranavirus strain provided protection for Micropterus salmoides by immersion immunization.

Largemouth bass ranavirus (LMBV) causes disease outbreaks and high mortality at all stages of largemouth bass farming. Therefore, live vaccine development is critical for largemouth bass prevention against LMBV by immersion immunization. Herein, an attenuated LMBV strain with good immunogenicity, designated as LMBV-2007136, was screened from the natural LMBV strains bank through challenge assay and immersion immunization experiment. After determing the safe concentration range of LMBV-2007136, the minimum immunizing dose of immersion immunization was verified. When largemouth bass were vaccinated by immersion at the lowest concentration of 102.0 TCID50/mL, all of fish were survival post virulent LMBV challenge, and the relative percent survival (RPS) was 100 %. And the immune gene expression levels of IL-10, IL-12, IFN-γ, and IgM in the spleen and kidney post-vaccination were significantly up-regulated compared to the control group, but TNF-α expression showed no significant changes. The safety and efficacy of LMBV-2007136 at passages P8, P13, and P18 were futher assessed, and no death of largemouth bass was observed within 21 days post-immunization and RPS of three vaccination groups was 100 %, suggesting that the safety and efficacy of the attenuated strain at different passages was stable. Furthermore, in the virulence reversion test, the attenuated strain was propagated through 5 times in largemouth bass by intraperitoneal injection and no abnormality and mortality were observed, further proving the attenuated vaccine candidate LMBV-2007136 was safe. These results proved that LMBV-2007136 could be a promising candidate for a live vaccine to protect largemouth bass from LMBV disease.

Expression of IL-1ß in transgenic Eimeria necatrix enhances the immunogenicity of parasites and promotes mucosal immunity against coccidiosis.

Anticoccidial vaccines comprising living oocysts of Eimeria tenella, Eimeria necatrix, Eimeria maxima, and Eimeria acervulina are used to control coccidiosis. This study explored the potential of IL-1ß to act as a molecular adjuvant for enhancing the immunogenicity of Eimeria necatrix and mucosal immunity. We engineered E. necatrix to express a functional chIL-1ß (EnIL-1ß) and immunized chickens with oocysts of the wild type (EnWT) and tranegenic (EnIL-1ß) strains, respectively. The chickens were then challenged with EnWT oocysts to examine the immunogenicity-enhancing potential of chIL-1ß. As expected, the oocyst output of EnIL-1ß-immunized chickens was significantly reduced compared to those immunized using EnWT. No difference in body weight gain and lesion scores of EnIL-1ß and EnWT groups was observed. The parasite load in the small intestine and caeca showed that the invasion and replication of EnIL-1ß was not affected. However, the markers of immunogenicity and mucosal barrier, Claudin-1 and avian ß-defensin-1, were elevated in EnIL-1ß-infected chickens. Ectopic expression of chIL-1ß in E. necatrix thus appears to improve its immunogenicity and mucosal immunity, without increasing pathogenicity. Our findings support chIL-1ß as a candidate for development of effective live-oocyst-based anticoccidial vaccines.

Immunization strategies for individuals with sickle cell anemia: A narrative review.

Sickle cell anemia (SCA) is a hereditary blood disorder characterized by the production of abnormal hemoglobin, leading to the formation of sickle-shaped red blood cells. These distorted cells can obstruct blood flow, causing vaso-occlusive crises and increasing the risk of severe infections due to functional asplenia and immune system dysregulation. Immunization is a crucial strategy to mitigate infection-related complications in individuals with SCA, necessitating a comprehensive and tailored vaccination approach. Current immunization guidelines for individuals with SCA recommend a combination of standard and additional vaccines to address their heightened susceptibility to infections. Key vaccines include pneumococcal conjugate (PCV13) and polysaccharide (PPSV23) vaccines, meningococcal conjugate (MenACWY) and serogroup B (MenB) vaccines, Haemophilus influenzae type b (Hib) vaccine, annual influenza vaccine, and hepatitis A and B vaccines. These vaccinations aim to provide broad protection against pathogens that pose significant risks to patients with SCA. Despite generally adequate immune responses, the variability in vaccine efficacy due to immune dysfunction necessitates booster doses and additional vaccinations. This narrative review highlights the importance of adhering to current immunization recommendations and addresses challenges such as access to care, vaccine hesitancy, and monitoring vaccination status.