Iridaea cordata lipid extract associated with the rCP01850 protein of C. pseudotuberculosis elicited a Th1 immune response in immunized sheep.

Sheep farming contributes to the socioeconomic development of small and medium-scale livestock farmers. However, several factors can hinder successful animal production, as is the case for infectious diseases, such as the one caused by Corynebacterium pseudotuberculosis, known as caseous lymphadenitis (CLA). CLA has >90% prevalence in Brazilian herds and antibiotic treatment is not effective, consequently causing significant economic losses to farmers. Given the above, effective vaccines need to be developed to prevent this disease. This study aimed to evaluate the adjuvant activity of the lipid extract from the macroalgae Iridaea cordata as a candidate for developing an effective vaccine formulation. For such, four groups of six sheep each were inoculated with sterile 0.9% saline solution (G1), rCP01850 (G2), rCP01850 + I. cordata (G3), and rCP01850 + saponin (G4). Each sheep received two vaccine doses 30 days apart. Total IgG production levels significantly increased in experimental groups G3 and G4 on days 30, 60, and 90. On day 90, G3 showed higher total IgG production (p < 0.05) when compared to G4. When analyzing cytokine production, G3 was the only experimental group with significantly increased IFN-γ, IL-12, TNF-α, and IL-10 mRNA expression levels. Our results show the vaccine formulation containing rCP01850 adjuvanted with the I. cordata lipid extract elicited a Th1 immune response in sheep, indicating I. cordata lipid extract may be a promising adjuvant for developing an effective vaccine against infection caused by C. pseudotuberculosis.

[On the issue of qualitative assessment of level of population commitment to vaccination].

This article presents analysis of results of quantitative study "Level of Commitment to Vaccination" based on author's original methodology of survey. The main medical and social causes of decreasing of level of population commitment to vaccination are explained. The purpose of the study is to quantitatively assess commitment to vaccination, to establish both dependence of level of commitment on risk factors of population refusal to be vaccinated and medical and social causes of this phenomenon. Materials and methods. In April-June 2023, sociological survey of respondents (n=300) aged from 19 to 75 years using the author's methodology was implemented. The statistical processing of materials was carried out using statistical software SPSS Statistics 23.0 using correlation analysis and descriptive statistics. The results and discussion. Using correlation analysis (according r-Spearman), dependence of level of commitment on number of medical and social factors was established. The readiness to vaccination depends on degree of trust to medicine. The accessibility of information about National Vaccination Calendar, vaccination scheme and vaccine effectiveness directly impact decision to be vaccinated. Conclusion. The development of complex of measures (technologies) improving population literacy through organization of informational and educational environment will reduce the number of unjustified refusals and increase level of population commitment to vaccination in general.

Screening for viral hepatitis carriage.

Viral hepatitis during pregnancy is common globally. In this review, we focus on the antenatal screen for hepatitis A, B, C and E, the prevention of mother-to-child transmission (MTCT) of hepatitis B and C, and the management of hepatitis A, B, C and E during pregnancy. Neonatal timely administration of hepatitis B immunoglobulin and hepatitis B vaccine is the cornerstone for preventing MTCT of hepatitis B virus (HBV), and perinatal antiviral prophylaxis with tenofovir disoproxil fumarate in mothers with positive HBeAg or HBV DNA >2 × 105 IU/ml also plays important roles in further reducing MTCT. Avoidance of risk practices in managing labor and delivery process of women with HCV infection may be useful to reduce MTCT of HCV. Early recognition of severe hepatic injury or liver failure associated with hepatitis viruses by regular liver function tests is critical to prevent maternal mortality associated with hepatitis.

Respiratory Syncytial Virus: Epidemiology, Burden of Disease, and Clinical Update.

Respiratory syncytial virus (RSV) is a common viral pathogen that accounts about 33 million cases of acute lower respiratory tract infection (LRTI) worldwide in children under the age of 5 years each year. High-risk populations, particularly preterm infants, those with underlying chronic lung disease, congenital heart disease, or compromised immune systems, are afflicted most significantly. RSV infection is characterized by significant amount of mucus and submucosal edema in the respiratory tract, leading to congestion and, oftentimes, significant respiratory distress. Antigen- and PCR-based testing are used to diagnose RSV infection.

MIP vaccine in leprosy: A scoping review and future horizons.

Mycobacterium Indicus Pranii (MIP) vaccine is a killed vaccine developed in India for leprosy with immunotherapeutic as well as immunoprophylactic effects. MIP, earlier known as Mycobacterium welchii, is a rapidly growing non-pathogenic mycobacterium. The novelty of this bacterium is due to its translational application as an immunotherapeutic agent. When administered intradermally, the vaccine induces cell-mediated immunity in the host towards Mycobacterium leprae. It leads to faster clinical and histopathological improvement, rapid bacillary clearance, and also lepromin conversion in anergic leprosy patients. The beneficial role of the MIP vaccine in augmenting the therapeutic efficacy of Multidrug Therapy (MDT), particularly in highly bacillated leprosy patients, is well documented in various studies from India. The role of the vaccine in reactional states is controversial, with varied results in different studies. Overall, it is found to decrease the frequency of type 2 lepra reactions and is useful in recalcitrant erythema nodosum leprosum. Even though there may be an increased likelihood of type 1 reactions, no additional nerve function impairment is attributed to the vaccine in various studies. In household contacts of leprosy who are administered MIP, it is noted to confer protection from disease lasting up to 10 years. It may prove to be a cost-effective strategy in national leprosy programmes. Apart from local injection site reactions, the vaccine is relatively safe, but it is not recommended in pregnancy and lactation. This article provides an overview of the MIP vaccine's clinical application in the context of leprosy spanning over 40 years. It also considers the vaccine's possible future applications in the management of disease-related complications and achieving the long-term goal of zero leprosy.

BCG and bladder cancer. Forty-eight years after Morales report.

Although BCG use as an anticancer drug was nearly abandoned due to the poor results in most tumors, in 1976 Morales reported a relevant reduction in recurrence with intravesical BCG in few patients affected by NMIBC. Since then BCG was globally accepted as an empirical and effective therapy in treating Tis and preventing recurrence of intermediate and high risk NMIBC. Forty-eight years after Morales' report, although some open questions remain object of debate, we have been able to find answers to many doubts improving BCG activity and toxicity. We better select patients undergoing BCG and many trials have indicated the best dosage and schedule. Moreover, we are able to better identify the patient unresponsive to BCG who might benefit of a timely radical cystectomy. We are also aware of the difficulties and toxicities that can be encountered with BCG use in every-day clinical practice. Research is ongoing to obtain genetically modified BCG to increase its efficacy and reduce toxicity. Moreover, the combination of BCG with other immunotherapeutic drugs given intravesically or systemically, first immune checkpoint inhibitors, is under study to obtain a response in patients unresponsive or intolerant to BCG. Almost 50 years after Morales publication, intravesical BCG remains an inalienable tool against NMIBC.

The effect of gastrointestinal graft-versus-host disease and diarrhea on the pharmacokinetic profile of sotrovimab in hematopoietic stem cell transplant recipients.

BACKGROUND: Monoclonal antibodies (mAbs) are utilized broadly to treat cancer and infectious diseases, and mAb exposure (serum concentration over time) is one predictor of overall treatment efficacy. Herein, we present findings from a clinical trial evaluating the pharmacokinetics (PK) of the long-acting mAb sotrovimab targeting SARS-CoV-2 in hematopoietic cell transplant (HCT) recipients. METHODS: All participants received an intravenous infusion of sotrovimab within one week prior to initiating the pre-transplant preparative regimen. The serum concentration of sotrovimab was measured longitudinally for up to 24 weeks post-transplant. RESULTS: Compared to non-HCT participants, we found that mAb clearance was 10% and 26% higher in autologous and allogeneic HCT recipients, respectively. Overall sotrovimab exposure was approximately 15% lower in HCT recipients compared to non-HCT recipients. Exposure was significantly reduced in HCT recipients who developed diarrhea and lower gastrointestinal (GI) graft-versus-host disease (GVHD) post-transplant. CONCLUSIONS: These data show that sotrovimab exposure may be reduced in HCT recipients, possibly related to increased GI clearance in patients with GVHD. This phenomenon has implications for dose selection and duration of efficacy with sotrovimab and potentially other mAbs in this vulnerable patient population. Thus, mAb dose regimens developed in non-HCT populations may have to be optimized when applied to HCT populations.

A Historical Perspective on Respiratory Syncytial Virus Prevention: A Journey Spanning Over Half a Century From the Setback of an Inactive Vaccine Candidate to the Success of Passive Immunization Strategy.

The efforts to prevent respiratory syncytial virus (RSV) infection in infants span over half a century. RSV vaccine development began in the 1960s, and it confronted a significant disappointment after testing a formalin-inactivated RSV (FI RSV) vaccine candidate. This inactivated RSV vaccine was not protective. A large number of the vaccinated RSV-naive children, when subsequently exposed to natural RSV infection from wild-type virus in the community, developed severe lung inflammation termed enhanced respiratory disease. This resulted in a halt in RSV vaccine development. In the 1990s, attention turned to the potential for passive protection against severe RSV disease with immunoglobulin administration. This led to studies on using standard intravenous immunoglobulins in high-risk infants, followed by high-titer RSV immunoglobulin preparation and, subsequently, the development of RSV monoclonal antibodies. Over the past 25 years, palivizumab has been recognized as a safe and effective monoclonal antibody as a prevention strategy for RSV in high-risk children. Its high cost and need for monthly administration, however, has hindered its use to ~2% of the birth cohort, neglecting the vast majority of newborns, including healthy full-term infants who comprise the largest portion of RSV hospitalizations and the greatest part of the burden of RSV disease. Still these efforts, helped pave the way for the present advances in RSV prevention that hold promise for mitigating severe RSV disease for all infants.

Immunoactive Prophylaxis Protocol of Uncomplicated Recurrent Urinary Tract Infections in a Cohort of 1104 Women Treated with Uromune® Vaccine.

BACKGROUND: A prospective, descriptive, and multicenter research that included 1104 women with three or more uncomplicated UTIs following immunoprophylaxis with Uromune® vaccine between 2011 and 2022 is presented. OBJECTIVE: to analyze the efficacy of Uromune® and perform a follow-up protocol. VARIABLES: age; bacteria; number of UTIs at baseline and at 3, 6, and 12 months of follow-up; distribution according to age and months of the year; therapy with polybacterial vaccine or autovaccine. Efficacy was defined as 0-2 UTIs during follow-up. Patients were divided into Group 1, with 3-4 UTIs at baseline, and Group 2, with 5 or more. RESULTS: Average age was 72. Escherichia coli represented 64.3% of infections. Overall efficacy was 91.7%, 82.3%, and 57.6% at 3, 6, and 12 months. Efficacy in patients treated with vaccines was 95.8%, 88.4%, and 56.1%, and with autovaccines it was 85.7%, 73.6%, and 60.2%. Results were statistically significant in relation to vaccines (p < 0.05). Group 1 represented 65.2% and Group 2 represented 34.8%. Group 1 had an efficacy of 97.7%, 91.1%, and 64.7% and Group 2 had an efficacy of 80.2%, 64.3%, and 40%. Results were statistically significant in Group 1 (p < 0.05). CONCLUSIONS: Patients at baseline with less than five UTIs will have better result and would benefit from a prophylaxis protocol with Uromune®.

Rh immune globulin immunoprophylaxis after RhD-positive red cell exposure in RhD-negative patients via transfusion: A survey of practices.

BACKGROUND: Current Association for the Advancement of Blood & Biotherapies (AABB) standards require transfusion services to have a policy on Rh immune globulin (RhIG) immunoprophylaxis for when RhD-negative patients are exposed to RhD-positive red cells. This is a survey of AABB-accredited transfusion services in the United States (US) regarding institutional policies and practices on RhIG immunoprophylaxis after RhD-negative patients receive RhD-positive (i.e., RhD-incompatible) packed red blood cell (pRBC) and platelet transfusions. RESULTS: Approximately half of the respondents (50.4%, 116/230) have policies on RhIG administration after RhD-incompatible pRBC and platelet transfusions, while others had policies for only pRBC (13.5%, 31/230) or only platelet (17.8%, 41/230) transfusions, but not both. In contrast, 18.3% (42/230) report that their institution has no written policies on RhIG immunoprophylaxis after RhD-incompatible transfusions. Most institutions (70.2%, 99/141) do not have policies addressing safety parameters to mitigate the risk of hemolysis associated with the high dose of RhIG required to prevent RhD alloimmunization after RhD-incompatible pRBC transfusions. DISCUSSION: With approximately half of US AABB-accredited institutions report having policies on RhIG immunoprophylaxis after both RhD-incompatible pRBC and platelet transfusions, some institutions may not be in compliance with AABB standards. Further, most with policies on RhIG immunoprophylaxis after RhD-incompatible pRBC transfusion do not have written safeguards to mitigate the risk of hemolysis associated with the high dose of RhIG required. CONCLUSION: This survey underscores the diverse and inadequate institutional policies on RhIG immunoprophylaxis after RhD exposure in Rh-negative patients via transfusion. This observation identifies an opportunity to improve transfusion safety.

Neutralizing activity of anti-respiratory syncytial virus monoclonal antibody produced in Nicotiana benthamiana.

Respiratory syncytial virus (RSV) is a highly contagious virus that affects the lungs and respiratory passages of many vulnerable people. It is a leading cause of lower respiratory tract infections and clinical complications, particularly among infants and elderly. It can develop into serious complications such as pneumonia and bronchiolitis. The development of RSV vaccine or immunoprophylaxis remains highly active and a global health priority. Currently, GSK's Arexvy™ vaccine is approved for the prevention of lower respiratory tract disease in older adults (>60 years). Palivizumab and currently nirsevimab are the approved monoclonal antibodies (mAbs) for RSV prevention in high-risk patients. Many studies are ongoing to develop additional therapeutic antibodies for preventing RSV infections among newborns and other susceptible groups. Recently, additional antibodies have been discovered and shown greater potential for development as therapeutic alternatives to palivizumab and nirsevimab. Plant expression platforms have proven successful in producing recombinant proteins, including antibodies, offering a potential cost-effective alternative to mammalian expression platforms. Hence in this study, an attempt was made to use a plant expression platform to produce two anti-RSV fusion (F) mAbs 5C4 and CR9501. The heavy-chain and light-chain sequences of both these antibodies were transiently expressed in Nicotiana benthamiana plants using a geminiviral vector and then purified using single-step protein A affinity column chromatography. Both these plant-produced mAbs showed specific binding to the RSV fusion protein and demonstrate effective viral neutralization activity in vitro. These preliminary findings suggest that plant-produced anti-RSV mAbs are able to neutralize RSV in vitro.

Early estimates of nirsevimab immunoprophylaxis effectiveness against hospital admission for respiratory syncytial virus lower respiratory tract infections in infants, Spain, October 2023 to January 2024.

The monoclonal antibody nirsevimab was at least 70% effective in preventing hospitalisations in infants with lower respiratory tract infections (LRTI) positive for respiratory syncytial virus (RSV) in Spain (Oct 2023-Jan 2024), where a universal immunisation programme began late September (coverage range: 79-99%). High protection was confirmed by two methodological designs (screening and test-negative) in a multicentre active surveillance in nine hospitals in three regions. No protection against RSV-negative LRTI-hospitalisations was shown. These interim results could guide public-health decision-making.

Development and characterization of a novel neutralizing scFv vectored immunoprophylaxis against botulinum toxin type A.

Botulinum toxin is a protein toxin secreted by Clostridium botulinum that is strongly neurotoxic. Due to its characteristics of being super toxic, quick acting, and difficult to prevent, the currently reported antiviral studies focusing on monoclonal antibodies have limited effectiveness. Therefore, for the sake of effectively prevention and treatment of botulism and to maintain country biosecurity as well as the health of the population, in this study, we intend to establish a single chain antibody (scFv) targeting the carboxyl terminal binding functional domain of the botulinum neurotoxin heavy chain (BONT/AHc) of botulinum neurotoxin type A, and explore the value of a new passive immune method in antiviral research which based on adeno-associated virus (AAV) mediated vector immunoprophylaxis (VIP) strategy. The scFv small-molecular single-chain antibody sequenced, designed, constructed, expressed and purified by hybridoma has high neutralising activity and affinity level, which can lay a good foundation for the modification and development of antibody engineering drugs. In vivo experiments, AAV-mediated scFv engineering drug has good anti-BONT/A toxin neutralisation ability, has advantages of simple operation, stable expression and good efficacy, and may be one of the effective treatment strategies for long-term prevention and protection of BONT/A botulinum neurotoxin.

Society for Maternal-Fetal Medicine Consult Series #69: Hepatitis B in pregnancy: updated guidelines.

More than 290 million people worldwide, and almost 2 million people in the United States, are infected with hepatitis B virus, which can lead to chronic hepatitis B, a vaccine-preventable communicable disease. The prevalence of chronic hepatitis B infection in pregnancy is estimated to be 0.7% to 0.9% in the United States, with >25,000 infants born annually at risk for chronic infection due to perinatal transmission. Given the burden of disease associated with chronic hepatitis B infection, recent national guidance has expanded both the indications for screening for hepatitis B infection and immunity and the indications for vaccination. The purpose of this document is to aid clinicians caring for pregnant patients in screening for hepatitis B infection and immunity status, discuss the perinatal risks of hepatitis B infection in pregnancy, determine whether treatment is indicated for maternal or perinatal indications, and recommend hepatitis B vaccination among susceptible patients. The following are the Society for Maternal-Fetal Medicine recommendations: (1) we recommend triple-panel testing (hepatitis B surface antigen screening, antibody to hepatitis B surface antigen, and total antibody to hepatitis B core antigen) at the initial prenatal visit if not previously documented or known to have been performed (GRADE 1C); (2) we recommend universal hepatitis B surface antigen screening alone at the initial prenatal care visit for all pregnancies where there has been a previously documented negative triple-panel test (GRADE 1B); (3) we recommend that individuals with unknown hepatitis B surface antigen screening status be tested on any presentation for care in pregnancy; we also recommend that those with clinical hepatitis or those with risk factors for acute hepatitis B infection be tested at the time of admission to a birthing facility when delivery is anticipated (GRADE 1B); (4) we do not recommend altering routine intrapartum care in individuals chronically infected with hepatitis B; administration of neonatal immunoprophylaxis is standard of care in these situations (GRADE 1B); (5) we do not recommend cesarean delivery for the sole indication of reducing perinatal hepatitis B virus transmission (GRADE 1B); (6) we recommend that individuals with HBV infection can breastfeed as long as the infant has received immunoprophylaxis at birth (GRADE 1C); (7) we suggest individuals with hepatitis B infection who desire invasive testing may have the procedure performed after an informed discussion on risks and benefits in the context of shared decision-making and in the context of how testing will affect clinical care (GRADE 2C); (8) in individuals with hepatitis viral loads >200,000 IU/mL (>5.3 log 10 IU/mL), we recommend antiretroviral therapy with tenofovir (tenofovir alafenamide at 25 mg daily or tenofovir disoproxil fumarate at 300 mg daily) in the third trimester (initiated at 28-32 weeks of gestation) as an adjunctive strategy to immunoprophylaxis to reduce perinatal transmission (GRADE 1B); (9) we recommend administering hepatitis B vaccine and hepatitis B immunoglobin within 12 hours of birth to all newborns of hepatitis B surface antigen-positive pregnant patients or those with unknown or undocumented hepatitis B surface antigen status, regardless of whether antiviral therapy has been given during the pregnancy to the pregnant patient (GRADE 1B); and (10) we recommend hepatitis B vaccination in pregnancy for all individuals without serologic evidence of immunity or documented history of vaccination (GRADE 1C).

Early lessons from the implementation of universal respiratory syncytial virus prophylaxis in infants with long-acting monoclonal antibodies, Galicia, Spain, September and October 2023.

A monoclonal antibody for universal respiratory syncytial virus prophylaxis in infants has recently been licensed. We share our experiences of integrating nirsevimab into the regional immunisation programme in Galicia, Spain. After a 3-week hospital-based immunisation campaign with flexible individualised appointments and educational activities, nirsevimab uptake was 97.5% in the high-risk group, 81.4% in the catch-up group and 92.6% in infants born during the campaign. This successful implementation strategy can serve as a model and may inform other countries' programmatic deliberations.

New Insights on Respiratory Syncytial Virus Prevention.

Respiratory syncytial virus (RSV) is a well-known infant pathogen transmitted mainly by droplets. It is a leading cause of upper respiratory tract infections in children, usually with a mild course of illness. RSV has also been a threat to older people, especially those with underlying medical conditions. For a long time, prevention was limited to passive immunoprophylaxis with palivizumab for high-risk infants. There was a strong need to find other treatment or prevention methods against RSV infections. In addition, after the coronavirus disease 2019 (COVID-19) pandemic, some significant changes in RSV epidemiology have been observed. Researchers noticed the shift in RSV seasonality and age distribution and the increased number of cases in older infants and adults. All of these made the need to find other medical options even stronger. Fortunately, two protein-based vaccines against RSV have successfully passed all phases of clinical trials and have been approved for use by adults and older people. One of them is also approved for infants from birth to 6 months of age (after maternal immunisation during pregnancy) and for pregnant women between 24 and 36 weeks of pregnancy. Also, a new passive immunisation option named nirsevimab (a highly potent monoclonal antibody with a long half-life) is now available for the paediatric group. In this review, we will discuss the previous and current RSV prevention methods in the light of structural discoveries of RSV antigens.

Effect of the interval between birth and second dose of hepatitis B vaccine on perinatal transmission of hepatitis B virus.

Preventing perinatal transmission is important for hepatitis B (HepB) elimination. We conducted a retrospective cohort study to assess the interval between HepB birth-dose (HepB-BD) to second-dose (HepB-SD) vaccination on perinatal transmission. Among 39,313 infants born to HepB s-antigen (HBsAg)-positive mothers from a Korean national database 38,411 (97.7%) had completed timely immunophylaxis with HepB-BD 41,572 (99.8%) with hepatitis B immune globulin, and 1027 (2.6%) were HBsAg-positive at ≥ 9 months. Maternal factors (i.e. HepB e-antigen status, age, or nationality) were associated with an increased risk of infection whereas short gestational length decreased it. The HepB-BD - HepB-SD interval (<8 vs. ≥8 weeks) did not alter the risk.

Fc-mediated functions of nirsevimab complement direct respiratory syncytial virus neutralization but are not required for optimal prophylactic protection.

Introduction: Nirsevimab is an extended half-life (M252Y/S254T/T256E [YTE]-modified) monoclonal antibody to the pre-fusion conformation of the respiratory syncytial virus (RSV) Fusion protein, with established efficacy in preventing RSV-associated lower respiratory tract infection in infants for the duration of a typical RSV season. Previous studies suggest that nirsevimab confers protection via direct virus neutralization. Here we use preclinical models to explore whether fragment crystallizable (Fc)-mediated effector functions contribute to nirsevimab-mediated protection. Methods: Nirsevimab, MEDI8897* (i.e., nirsevimab without the YTE modification), and MEDI8897*-TM (i.e., MEDI8897* without Fc effector functions) binding to Fc γ receptors (FcγRs) was evaluated using surface plasmon resonance. Antibody-dependent neutrophil phagocytosis (ADNP), antibody-dependent cellular phagocytosis (ADCP), antibody-dependent complement deposition (ADCD), and antibody-dependent cellular cytotoxicity (ADCC) were assessed through in vitro and ex vivo serological analyses. A cotton rat challenge study was performed with MEDI8897* and MEDI8897*-TM to explore whether Fc effector functions contribute to protection from RSV. Results: Nirsevimab and MEDI8897* exhibited binding to a range of FcγRs, with expected reductions in FcγR binding affinities observed for MEDI8897*-TM. Nirsevimab exhibited in vitro ADNP, ADCP, ADCD, and ADCC activity above background levels, and similar ADNP, ADCP, and ADCD activity to palivizumab. Nirsevimab administration increased ex vivo ADNP, ADCP, and ADCD activity in participant serum from the MELODY study (NCT03979313). However, ADCC levels remained similar between nirsevimab and placebo. MEDI8897* and MEDI8897*-TM exhibited similar dose-dependent reduction in lung and nasal turbinate RSV titers in the cotton rat model. Conclusion: Nirsevimab possesses Fc effector activity comparable with the current standard of care, palivizumab. However, despite possessing the capacity for Fc effector activity, data from RSV challenge experiments illustrate that nirsevimab-mediated protection is primarily dependent on direct virus neutralization.