Auswahl der wissenschaftlichen Literatur zum Thema „Immunization schemes“

Most illegal Ponzi schemes are ultimately out of control and lead to systemic financial risk. Risk education and precaution are similar to mass random immunization of epidemic spreading. In this study, the effect of random immunization strategy is evaluated based on the potential-investor–divestor (PID) spreading model in both homo- and inhomogeneous social networks. Fund flux function and system balance function are formulated. The zero point of system balance is used as the collapse point. The peak value of balance, the total number of investors involved and the total amount of principal involved are defined to compare the immunization effects in various scenarios. Mathematical derivation and numerical simulation show that the random immunization takes effect by postponing the peak position of the system balance as well as suppressing the peak values of the system balance. This kind of positive effect helps reduce the scheme’s scale of total number of investors involved and total amount of principal involved. The random immunization is more powerful towards the schemes with small spreading rate than those with medium and high spreading rates. Hence, it is suitable for the concentrated regulation on a large amount of small scale and slow spreading schemes in bulk.

The results of specific immunization of hospital health workers with domestic hepatitis B «Combiotech» vaccine indicate its high immunological and epidemiological efficiency. Protective level of collective immunity was established during surveillance according to the standard vaccination scheme, and epidemiological protectability over a period of the emergency vaccination scheme with the threat of professional infection. The marked lack of hepatitis B cases among vaccinated persons when carrying out immunization according to standard and emergency schemes as well as a significant reduction of the morbidity of medical staff of various clinical forms of the infection got registered. Use of domestic preparation taking into account two serotypes of ayw and adw which are contained in vaccines against hepatitis B is advisable.

Background. One of the effective ways to maintain the epidemic well-being of vaccine preventable diseases is to estimate immunization rates and coverage.Objective. The aim of the study is to conduct comparative analysis of immunization levels among children in various regions of Russian Federation. Methods. Children aged from 6 months to 15 years conducted comparative analysis of indicators of documented immunization and immunization coverage according to forms 112/y and 036/y in four federal districts of Russian Federation. The immunization rate was estimated in individuals who had completed vaccination scheme according to the national immunization schedule (NIS) (of 2014). Immunization coverage was estimated by number of persons with at least one vaccination in past medical history.Results. The analysis was performed on 2687 children medical records from the Central, Ural, Siberian and Volga federal districts (FD). BCG immunization rates in all FDs tend to be 100%. There are high levels of immunization against hepatitis B, as well as against measles, rubella and parotitis (the lowest values are noted in the Central Federal District: against hepatitis B — 74%, against measles, rubella, mumps — 69%, high — in the Volga Federal District: against hepatitis B — 95%, against measles, rubella, mumps — 97%). There is significant mismatch in immunization rates and immunization coverage for pertussis, diphtheria, tetanus and poliomyelitis in all FDs (from 20% to 40%) indicating that there are disturbances in vaccination schemes. Low immunization rates are noted against pneumococcal infection (from 12% in the Siberian Federal District to 36% in the Volga Federal District) and influenza (from 0.5% in the Volga Federal District to 9% in the Ural Federal District).Conclusion. The highest immunization rates for all infections included in the NIS (apart from influenza) were revealed in the Volga Federal District. Influenza immunization rate is critically low in all FDs.

Abstract Vaccination needs to prepare the immune system to rapidly secrete specific antibodies upon a future encounter with the pathogen. Assessments of this feature are often challenging to perform, as measurements using antibody titers represent only a poorly resolved average of the rapidly evolving repertoire. We recently published and described a novel, droplet-based microfluidic technology that allows the quantitative characterization of humoral immune responses with single-cell and -antibody resolution. The employed snapshot analysis in this system enables studying even rapidly evolving repertoires. Additionally, the method extracts for each secreted antibody its production rate, specificity, and affinity, offering a high-resolution view of immunization. Consequently, this system enables the investigation of the immunization-generated secreted antibody repertoire with high temporal, analytical, and spatial resolution. This study in mice used the above method to characterize the quality of the immunization-induced immunoglobulin-G repertoire, and we correlated these measures with the recall-accessible repertoire. Here, we showed that introducing variation in the immunization schemes led to significant differences in the secreted repertoire. Additional analysis after recall allowed quantifying the accessible antibody repertoire, and due to the single-cell resolution, our data allowed us to compare these two repertoires on a phenotypical level. We showed that the relationships between the two repertoires are not trivial and strongly depend on immunization itself. In summary, the developed approach introduced a novel, quantitative, and functionally resolved alternative to study the quality of immunizations.

For power plant boiler combustion control system has large inertia, nonlinear and other complex characteristics, a control algorithm of PID optimized by means of adaptive immune genetic algorithm is presented. A variety of improved schemes of GA were designed, include: initial population generating scheme, fitness function design scheme, immunization strategy, adaptive crossover probability and adaptive mutation probability design scheme. By taking the rise time, error integral and overshoot of system response as the performance index, and using genetic algorithm for real-coded of PID parameters, then a group of optimal values were obtained. Simulation results show that the method has a good dynamic performance, superior to the conventional PID controller.

In this paper, we present an Human Immunodeficiency Virus (HIV)/Acquired Immune Deficiency Syndrome (AIDS) drug-resistant model using an ordinary differential equation (ODE) model on scale-free networks. We derive the threshold for the epidemic to be zero in infinite scale-free network. We also prove the stability of disease-free equilibrium (DFE) and persistence of HIV/AIDS infection. The effects of two immunization schemes, including proportional scheme and targeted vaccination, are studied and compared. We find that targeted strategy compare favorably to a proportional condom using has prominent effect to control HIV/AIDS spread on scale-free networks.

Improving specific prevention of tuberculosis continues to be a top priority in phthisiology. “Prime-boost” vaccination schemes aim to maintain adequate levels of specific immunity while forming long-term protection. They are based on sequential use of BCG vaccine and new vaccine candidates expressing protective mycobacterial proteins. The development of new tuberculosis prevention approaches requires an understanding of how the anti-tuberculosis immune response forms and which mechanisms provide TB protection. Since tuberculosis is an airborne infection, vaccine effectiveness largely depends on mucosal immunity based on the formation of long-lived, functionally-active memory T-lymphocytes in the respiratory tract. We have previously shown that the influenza vector expressing ESAT-6 and Ag85A mycobacterial proteins (Flu/ESAT-6_Ag85A) in vaccination scheme of intranasal boost immunization resulted in significant increase of BCG's protective effect according to key indicators aggregate data in experimental tuberculosis infection. The aim of this work was to study the effect of intranasal immunization with the Flu/ESAT-6_Ag85A influenza vector on the formation of antigen-specific central and effector memory T cells and the cytokine-producing activity of effector T cells (TEM) in BCG standard and “BCG prime — influenza vector boost” vaccination schemes in mice. Intranasal immunization with the influenza vector has been shown to increase the proportion of antigen-specific CD4+ central memory T cells (TCM) in the pool of activated lymphocytes of lung and spleen reaching significant differences from the BCG group in the percentage of spleen CD4+ TCM (p < 0.01). In contrast to BCG, vaccination with the studied vaccine candidate was accompanied by accumulation of highly differentiated CD8 effector cells in lung, the target organ during tuberculosis infection. Comparative evaluation of the cell-mediated, post-vaccine immune response after immunization with influenzavector-based vaccine candidate (intranasal/mucosal) or BCG vaccine (subcutaneous) showed advantages in the mucosal group: in formation of functionally active subpopulations of effector CD4 and CD8 T lymphocytes (CD44highCD62Llow) in lungs secreting IL-2 as well as polyfunctional cells capable of coproducing two cytokines (IFNγ/TNFα or IFNγ/IL-2) or three cytokines (IFNγ/TNFα/IL-2). Due to their more pronounced effector function, polyfunctional T-lymphocytes can be considered to be potential immunological markers of protective immunity in tuberculosis.

The aim of this review was to investigate the use of the vaccines based on vaccinia virus, MVA stain, and adenovirus vectors for the prevention of Ebola virus disease. The recombinant MVA strains expressing antigen determinants of Filoviridae family representatives were assessed as possible candidates for vaccine preparations. Application of this virus as a vaccine vector is conditioned by the absence of herd immunity to smallpox and its safety for healthy adult volunteers, children, adolescents, individuals suffering from tuberculosis, persons aged 56–80 years, people with diagnosed atopic dermatitis, AIDS. Furthermore, immunization with the vaccine on the basis of vaccinia virus, MVA strain, does not cause complications associated with cardiovascular diseases. Preclinical trials on immunogenicity and protective efficiency were carried out on immune-competent and immune-compromised mice; guinea pigs adapted to Ebola virus; rhesus macaques and cynomolgus monkeys. Presented are the results of experiments on the creation of vaccines expressing either only viral glycoprotein or viral glycoprotein and structural protein Vp40. Given that Ebola fever and other filovirus infection outbreaks are hard to predict, multivalent vaccines that would be able to provide protection against all filovirus species were designed. Clinical trials on simultaneous use of the vaccines based on recombinant adenovirus vectors and MVA strain showed more pronounced safety of vaccines on the basis of recombinant MVA strain. Studies of humoral and T-cell immune responses have revealed that this vector is more suitable for booster vaccination in case of heterologous prime/booster immunization scheme. Vaccination regimens for forming strong durable immune responses have been analyzed. Epidemiological modeling provided evidence that preventive immunization leading to long-term immunity in healthy population in areas of high epidemic risk will be of greater benefit in terms of controlling future outbreaks compared to ring immunization that was effective during smallpox eradication campaign. Increased immunity level, induced by prime/booster vaccination, persisting for a long period of time, will have an advantage over accelerated ring immunization; when the duration of protection is more significant than the speed it is formed at.

We report that mice immunized with a phosphate immunogen produced polyclonal catalytic antibodies (PCAbs) that catalysed the hydrolysis of carbaryl, a widely used broad-spectrum carbamate insecticide that exerts toxic effects in animals and humans. The reaction catalysed by the PCAbs (IgGs) obeyed Michaelis–Menten kinetics in vitro with the following values at pH8.0 and 25°C: Km≈ 8.0μM, kcat = 4.8×10−3–5.8×10−1, kcat/knon-cat = 5.6×101–6.8×103 (where knon-cat is the rate constant of the reaction in the absence of added catalyst). The PCAbs were also active in whole sera under physiological conditions in vitro. The PCAbs induced in vivo were also active in vivo, as immunization with the phosphate immunogen decreased the mouse blood concentration of carbaryl. To our knowledge, this is the first report demonstrating that active immunization generates antibodies possessing therapeutic catalytic function in vivo. We propose that active immunization schemes that induce enzymically active antibodies may provide a highly specific therapeutic approach for degrading toxic substances.

The review presents data on the role of respiratory agents in the pathogenesis of exacerbations of bronchial asthma and the impact of vaccination on the clinical course of the disease. The features of the formation of protective immunity in various immunization schemes are analyzed. In patients with bronchial asthma, the substantiation of the vaccination scheme with the advantage of priority administration of conjugated polysaccharide vaccine followed by the introduction of polysaccharide pneumococcal vaccine after 8 weeks is given. It was shown that vaccination against pneumococcal infection resulted in elimination from sputum S. pneumoniae. Influenza vaccination in patients with bronchial asthma reduced the frequency and duration of exacerbations. Combined vaccination against influenza and pneumococcal infections did not reduce the clinical and immunological effect.

La pandémie COVID-19 a posé des défis majeurs aux systèmes de santé mondiaux, notamment en raison de la capacité du SARS-CoV-2 à acquérir des mutations. Cela a entraîné l'émergence séquentielle de variants préoccupants (VOCs de l’anglais Variants of concern) tels que Alpha, Beta, Delta, et désormais Omicron qui circule sous forme de sous-variants successifs (BA.1, JN.1, KP.3). Ces VOCs soulèvent des questions sur leur capacité à échapper à la réponse immunitaire induite par une infection et/ou une vaccination. Alors que les campagnes de vaccination se poursuivent, il est crucial d'évaluer comment différents schémas d'immunisation conférés par la vaccination homologue ou hétérologue ainsi que par la combinaison d’une infection et de vaccination (immunité hybride), impactent la réponse immunitaire contre les variants émergents. Grâce à une cohorte prospective de soignants, ce projet de thèse visait à étudier la capacité des VOCs à échapper à la réponse immunitaire, l'efficacité des différents schémas d'immunisation, et la durabilité des réponses immunitaires générées. Nos résultats montrent que les variants Alpha et Beta échappent aux anticorps neutralisants induits par l'immunisation contre la souche ancestrale, indépendamment du schéma d'immunisation. Cette capacité d’échappement immunitaire s'étend au-delà des premiers variants, car Delta et Omicron ont aussi présenté une baisse significative de leur capacité à être neutralisés par les anticorps produits lors d’une immunisation préalable. Ces résultats soulignent la nécessité cruciale de prendre en compte l'évasion immunitaire spécifique aux variants pour définir les seuils de protection et adapter les stratégies de vaccination. En plus de l’échappement immunitaire des VOCs, l'affaiblissement de la réponse immunitaire contribue également à une diminution de la protection contre le SARS-CoV-2 au fil du temps. Nos résultats montrent que le type d'immunisation, infection ou vaccination, impact significativement le pic et la demi-vie des anticorps dirigés contre le domaine de liaison au récepteur (RBD de l’anglais Receptor binding domain). Cela nous a mené à étudier la réponse immunitaire induite par différents schémas de vaccination 6 mois après l'immunisation. Nous avons montré que l'immunité hybride conduit à une réponse immunitaire plus robuste en comparaison à l'immunité induite par l'infection ou la vaccination seule. Cette réponse améliorée est observée à travers divers paramètres tels que la capacité de neutralisation et le pool de cellules B mémoires, et se traduit par une protection significativement améliorée contre le variant Delta. Ainsi, les individus avec une immunité hybride ont un risque d'infection par Delta réduit de 4,5 fois par rapport à ceux ayant reçu une vaccination homologue. Ces résultats soulignent l'importance de prendre en compte ces différences dans les recommandations vaccinales. Néanmoins, des infections dites «breakthrough», c'est-à-dire survenant malgré une vaccination antérieure, sont souvent observées pendant l’ère Omicron chez des individus vaccinés ou même présentant une immunité hybride. Notre étude sur la réponse humorale après une infection «breakthourgh» par BA.1 a révélé que, bien que l'immunité hybride empêche l’augmentation des taux d'IgG4 anti-S et maintient une activité ADCC élevée, elle limite la diversification du pool de cellules B mémoires spécifiques du RBD par rapport à l'immunité induite par la vaccination. Ces résultats indiquent que l’infection «breakthrough» induit des réponses immunitaires distinctes selon les schémas d'immunisation antérieurs, soulignant l’intérêt de considérer l’historique d’immunisation pour personnaliser les recommandations vaccinales. En somme, les résultats obtenus lors de ce travail de thèse soulignent la nécessité d’établir des recommandations vaccinales en fonction des immunisations antérieures pour répondre efficacement aux capacités d’échappement immunitaire des VOCs en circulation
The COVID-19 pandemic has presented significant challenges to global healthcare, largely due SARS-CoV-2’s ability to acquire new mutations. This has led to the sequential emergence of variants of concern (VOCs) such as Alpha, Beta, Delta, and now Omicron that exhibited different successive subvariants (notably BA.1, JN.1, and KP.3). These VOCs have raised concerns about their capacity to escape the immune response induced by infection and/or vaccination. As vaccination campaigns continue worldwide, it is crucial to evaluate how different immunization schemes, including homologous and heterologous vaccinations as well as infection combined with vaccination (hybrid immunity), impact the immune response against emerging variants. With a prospective cohort of healthcare workers, this PhD project aimed to investigate i) the capacity of viral variants to escape the immune response, ii) the effectiveness of different immunization schemes, and iii) the durability of the resulting immune responses. Our findings indicated that the Alpha and Beta variants are able to escape neutralizing antibodies induced by immunization against the ancestral strain, regardless of the immunization scheme. This capacity for immune evasion extends beyond these earlier variants, as both the Delta and Omicron variants also demonstrated significant resistance to neutralization by antibodies elicited through prior immunization. Such findings underscore the critical need to consider variant-specific immune escape when establishing protection thresholds and updating vaccination strategies. In addition to viral immune escape the waning of the immune response also contributes to a decreased protection against SARS-CoV-2. Our results show that the type of immunization, i.e. infection or vaccination, significantly influences the peak levels and half-life of antibodies targeting the receptor binding domain (RBD). This led us to investigate the immune response induced by different immunization schemes 6 months post-immunization. In particular, we showed that hybrid immunity leads to a more robust immune response 6 months post-immunization compared to immunity induced by either infection or vaccination alone. This enhanced response is observed across various immunological parameters, such as neutralization capacity and the pool of memory B cells, and translates into significantly improved protection against the Delta variant. Individuals with hybrid immunity experienced a 4.5-fold reduction in the risk of Delta infection compared to those with immunity induced solely by homologous vaccination. These findings highlight the importance of considering these differences when formulating vaccination recommendations. Nevertheless, breakthrough infections, i.e. infections occurring despite previous vaccination, are frequently reported during the Omicron era among individuals fully-vaccinated and those with hybrid immunity. Our investigation into the humoral immune response following BA.1 breakthrough infection revealed that while hybrid immunity prevents an increase in anti-S IgG4 levels and maintains a high antibody-dependent cellular cytotoxicity (ADCC) activity, it limits the diversification of the RBD-specific memory B cell pool compared to vaccination-induced immunity. Hence, our results indicate that BA.1 breakthrough infection elicits distinct immune responses that vary based on prior immunization schemes, which emphasizes the interest to consider immunization history with the aim to personalize vaccination recommendations. Overall, the results obtained throughout this PhD project emphasize the need to incorporate prior immunization history into ongoing adjustments of vaccination strategies and policies to effectively address the evolving immune escape capabilities of VOCs

Although there is little disagreement on the magnitude and importance of alleviating malnutrition, its causation and control continue to be the subject of debate and research. Recent evidence suggests that many of the traditional food-based strategies to reduce malnutrition, such as food aid distribution programs, school feeding programs, and food stamps, as well as policies that intervene to affect the price of food such as subsidies and rationing schemes, have proven of limited effectiveness. One important reason is that the critical period of undernutrition is generally in utero and early life. Among the most vulnerable groups, particularly pregnant women and infants, the causes of malnutrition often have little to do with food access and availability. Instead, prenatal care, immunization programs, breastfeeding promotion, and generally raising the quality of child care and nurturing behaviors are paramount. Likewise, improving the sanitary and home environment, including interventions that enhance access to clean water and latrines and behaviors such as hand washing and boiling water, will contribute to reductions in infection and help break the cycle of disease and malnutrition. In the area of food-related interventions, among those that are critical to the production of improved health and nutritional outcomes are food supplementation and fortification schemes that address micronutrient deficiencies. At the same time, there is legitimate concern that misguided food interventions, particularly broad-based price subsidies, food stamps, and food aid may have a range of deleterious consequences. These range from contributing to the epidemic of obesity and related chronic disease, to having a negative impact on farmers and producer incentives and the functioning of food markets.

Chapter seven undertakes close analysis of municipal immunization schemes in Cork and Dublin in the wake of the Ring incident and in the face of impaired public health service provision attendant on wartime conditions. It argues that the municipal anti-diphtheria immunization scheme in Cork city was the only intervention mounted in Ireland or Britain to attain immunization rates comparable to those achieved in North America. In Dublin, failure to organize a comprehensive immunization scheme facilitated the recrudescence of diphtheria in numbers not witnessed since the pre-vaccine era, and increased diphtheria mortality left parents with a difficult decision to make: to present children for treatment to a compromised public health service or to expose them to a rampant, virulent, and increasingly fatal diphtheria infection.

Chapter three examines the rollout of anti-diphtheria schemes in the Irish Free State. It argues that a successful – albeit small-scale – anti-diphtheria scheme undertaken in Dundalk, Co. Louth, in 1927 influenced the introduction of new legislation designed to accommodate the rollout of a state-backed national anti-diphtheria immunization programme. An overview of the national picture is complemented by more in-depth analysis of local initiatives implemented by ‘front line’ medical officers in Dublin and Cork. These case studies highlight the dissimilar results obtained by a frugal and limited intervention in Dublin compared with the more comprehensive mass immunization scheme implemented by public health authorities in Cork. This chapter suggests that Cork city was the site of the largest anti-diphtheria immunization scheme ever undertaken in Ireland and Britain, the success of which drew national and international attention

Chapter six argues that by the end of 1936, the Irish Free State had come close to incepting an operational national anti-diphtheria immunization scheme. This is a noteworthy achievement, as state-backed anti-diphtheria schemes were not introduced as an intervention against this pressing public health issue in the rest of Europe until 1938 and were only pursued with any vigour when wartime conditions exacerbated the problem from 1940 onwards. If it had progressed unimpeded, the Free State intervention seemed destined to eliminate diphtheria, and to become the first established national childhood immunization programme in Europe. However, the death of Siobhán O’Cionnfaola in April 1937, and the subsequent controversy surrounding the Ring incident, asked serious questions of active immunization and ultimately undermined vaccine confidence among parents, practitioners, and politicians. This chapter will evaluate the impact of the Ring controversy and the social, political and medical implications left in the wake of the incident.

Chapter five examines the Ring College immunization disaster, in which 24 children reportedly contracted tuberculosis and one 12-year-old girl died following routine anti-diphtheria immunization. The existing historiography relating to the Ring incident has, without exception, insisted that Burroughs Wellcome Ltd mistakenly supplied a bottle of live tuberculosis in lieu of a bottle of the anti-diphtheria serum toxoid-antitoxin floccules (TAF), even though this charge was not substantiated by a High Court ruling in 1939.This chapter provides new evidence suggesting that liability for the tragedy lay not with Burroughs Wellcome Ltd, but with the local attending doctor and his advisors, who mounted a conspiracy to cover up initial negligence in administering the immunization scheme and subsequent perfunctory medical treatment of the affected children.

This chapter argues that by 1937, a medical infrastructure of Western hospitals and clinics already existed in Yunnan—many of which promoted Jennerian vaccination against smallpox, if not immunization against other diseases. This organization had hybrid origins in the efforts of French, British, and Chinese empires during the early twentieth century, although the province remained on the fringes of the emergent Nationalist medical administration until the late 1930s. Wartime biomedical experts in Kunming relied upon this limited but significant infrastructure to build a new vaccination scheme that sought universal coverage of urban and rural populations for the first time. Ultimately, the politics of medicine—and especially vaccination against smallpox—in prewar Yunnan reflected power struggles between empires for influence in the region. Like the Russian, Japanese, and local forces that battled for controlling interests in Manchuria, French and British imperial powers in Yunnan competed with each other as they engaged with local warlords; sought to build economic and transportation networks in the region; and used medicine, especially epidemic control, as a means of establishing influence.

Introduction: Human Papillomavirus (HPV) infections are a significant public health problem, playing a crucial role in the development of cervical cancer (CC). Although 80% to 90% of precursor lesions regress spontaneously, lack of knowledge about the disease, low adherence to immunization, and low adherence to Pap smear testing contribute to high mortality, with cervical cancer being the third most common neoplasm among women in Brazil in 2023, with 17,010 new cases estimated. There are more than 200 types of HPV, with genotypes 16 and 18 being the most oncogenic and associated with cancer. Despite the importance of vaccination in prevention, adherence is still low, highlighting the urgent need for more effective awareness and health education strategies. : To analyze, through a literature review, the relevance of health professionals in promoting health education about the Human Papillomavirus and its association with the development of cervical cancer among women. Methodology : The study was characterized as qualitative and exploratory in the literature review format. For the systematization process of the searches, publications related to the last five years (2019-2024) were considered, the databases: Scielo, BVS and Google Scholar were used, using the descriptors: Human Papillomavirus, HPV, Cervical Cancer, Health Education, Health Professionals, Vaccination. Results/Discussion : In the search for evidence on cervical cancer (CC), 200 studies were identified, of which 37 were analyzed in depth and 10 selected as main results. The main challenges identified include lack of knowledge and fear of the Pap smear, misinformation about HPV vaccination, and barriers such as religious taboos, lack of preventive exams, and geographic isolation. In addition, lack of health education and exclusion of victims of sexual violence from the HPV pre-exposure prophylaxis (PrEP) scheme were highlighted. In response, the update of the vaccination schedule to a single dose, according to Joint Technical Note No. 101 of 2024 - CGICI, includes vaccination for boys and girls aged 9 to 14, including those who have suffered sexual violence, and extends the HPV4 vaccine to people aged 15 to 45 using PrEP Prophylaxis for HIV. Health professionals in Primary Health Care play a crucial role in educating about HPV, promoting vaccination, performing preventive exams, and early identification of precursor lesions, contributing to the reduction of cervical cancer incidence and mortality. Conclusion:It is concluded that the work of health professionals, especially in Primary Health Care, is essential to increase women's knowledge about HPV, combat misinformation and clarify the relationship between this virus and cervical cancer. Through health education, promotion of vaccination and performance of preventive exams such as the Pap smear, these professionals play a crucial role in the prevention and control of this neoplasia. Furthermore, by addressing social and behavioral barriers, they contribute significantly to reducing the incidence and mortality of cervical cancer, highlighting the need to strengthen prevention strategies and integrated health care.

Bovine babesiosis, caused by the apicomplexan parasites Babesiabovisand B. bigemina, is a major tick borne disease of cattle with significant economic importance globally. The vectors of Babesia parasites are R. (Boophilus) annulatusand R. microplus. In Israel these parasites are transmitted manly by R. annulatus. The main goal of the proposal was developing and testing a novel B. bovisvaccine based on stably transfected attenuated B. bovisexpressing the anti-tick Bm86 antigen. This required generating a transfected- attenuated B. bovisparasite containing a bidirectional promoter expressing both, the gfp- bsd selectable marker and the tick vaccine antigen Bm86. The vaccine was tested for its ability to elicit protective immune responses against T. annulatusticks. Efficient control of babesiosis is based on a complex scheme of integrated management, including preventive immunization, anti-babesial chemotherapy and control of tick populations. Live vaccines based on attenuated parasites are the most effective measure to control babesiosis, and are currently used in several countries, including Israel. Live attenuated parasites lead to a chronic infection and development of strong and long term immunity in vaccinated cattle. Still, live vaccines have several limitations, including the difficulty to distinguish among vaccinated and naturally infected cattle and potential for sporadic outbreaks in vaccinated animals. Tick limitation is essential to control babesiosis but the main measure to reduce tick infestation is traditionally approached using acaricides, which is limited by environmental concerns and the development of resistance by the ticks. Alternative tick-control measures including the use of anti-tick vaccines are emerging, and at least partial protective immunity has been achieved against tick vectors by vaccination with recombinant protective tick antigens (ie: Bm86). In addition, the Babesia vaccine development toolbox has been recently expanded with the development of transfection technology in Babesia parasites. In this approved proposal we successfully developed a Babesia live attenuated transfected vaccine, which is able to express a B. bovisMSA-1 signal-Bm86 chimera and eGFP genes under the control of the B. bovisef- 1 and actin promoters respectively. Genetic analysis demonstrated specific stable integration of the transfected genes in the expected ef-1 locus, and immunofluorescence analysis confirmed expression of Bm86 in the surface of transfected parasites. When applied to splenectomized calves, the transfected parasites were able to cause persistent B. bovisinfection with production of antibodies reactive with Bm86 for at least six months. In addition, partial protection against ticks was also observed upon challenging the vaccinated animals with R. annulatuslarvae. However, when used on intact calves, the vaccine failed to elicit detectable immune responses against Bm86, and we are still in the process of interpreting the data and make necessary changes in our experimental approaches. Overall, the results obtained here represent a step forward towards the development of integrated vaccines against both ticks and tick –borne pathogens, using the Babesia attenuated parasites as a platform to the delivery of exogenous protective antigens