Immunoprophylactic Agent Research Articles

The impact of probiotic supplementation on dental and general health metrics in pediatric populations

Relevance. Acute respiratory infections account for over 90% of infectious diseases in children. These children are classified as frequently ill, representing a significant concern in contemporary pediatrics. The presence of odontogenic infections further depletes their immunity and acts as a persistent source of sensitisation for the child's body.Materials and methods. A clinical-laboratory longitudinal prospective study was conducted on 477 children aged 12 and 15 years. The children were categorised into groups based on their risk of developing caries (minimal, moderate, high). Oral health status was assessed using the DMF index, oral hygiene was evaluated using the OHI-S index, and periodontal tissue condition was assessed using the PMA index. The activity of cariogenic flora aggression enzymes was measured by the level of salivary sialidase. The child's health status was evaluated using the infection index and the recurrence index. The schoolchildren were recommended a course of a preparation consisting of a combination of the probiotic Streptococcus salivarius M18 (at least 5 x 10^8 CFU) and vitamin D3 (320 IU or 8 µg of vitamin D3) at a dosage of one tablet per day, taken sublingually, for two months twice a year.Results. The study identified moderate correlations between salivary sialidase levels and several indicators, including the gingivitis index, the quantity of dental plaque, and the increase in sialidase activity in saliva. The level of salivary sialidase is regarded as a marker for plaque formation and the extent of periodontal tissue inflammation. Comprehensive oral sanitation, coupled with the strategic use of immunoprophylactic agents, resulted in significant improvements in oral health indicators (OHI-S, PMA, caries reduction) and specific child health metrics (infection index, recurrence index). Additionally, there was a notable reduction in salivary sialidase levels. The method demonstrated the highest efficacy in 12-year-old children who were at high risk of developing caries.Conclusion. The obtained data should be considered when planning individual therapeutic and preventive measures for schoolchildren with varying risks of developing caries and differing overall health statuses. Probiotic-based preparations should be incorporated into these measures.

CTC-177, a novel drug-Fc conjugate, shows promise as an immunoprophylactic agent against multidrug-resistant Gram-negative bacterial infections.

The widespread emergence of antibiotic resistance including MDR in Gram-negative bacterial pathogens poses a critical challenge to the current antimicrobial armamentarium. To create a novel drug-Fc conjugate (DFC) that can be delivered at sustained and prolonged levels while simultaneously activating the host immune response to combat MDR Gram-negative infections. The Cloudbreak™ platform was used to develop DFCs consisting of a targeting moiety (TM) (a polymyxin-derived dimer) attached via a non-cleavable linker to an effector moiety (EM) (the Fc domain of human IgG1). In vitro activities of the DFCs were assessed by MIC testing. Neutropenic mouse models of thigh infection, septicaemia and pneumonia were used to evaluate in vivo efficacy. Pharmacokinetics were evaluated in mice and cynomolgus monkeys. A single prophylactic dose of our lead DFC, CTC-177, resulted in significantly decreased bacterial burdens and reduced inflammation comparable to daily treatment with colistin in septicaemia and pneumonia mouse models. Furthermore, CTC-177 prophylaxis was able to restore colistin efficacy in colistin-resistant septicaemia, reducing bacterial burdens beyond the limit of detection. Finally, CTC-177 displayed a long terminal half-life of over 24 and 65 h in mice and cynomolgus monkeys, respectively. These data support the continued development of Cloudbreak™ DFCs as broad-spectrum prophylactic agents against Gram-negative infections.

Bergenin potentiates BCG efficacy by enriching mycobacteria-specific adaptive memory responses via the Akt-Foxo-Stat4 axis

The extensive inability of the BCG vaccine to produce long-term immune protection has not only accelerated the disease burden but also progressed towards the onset of drug resistance. In our previous study, we have reported the promising effects of Bergenin (Berg) in imparting significant protection as an adjunct immunomodulator against tuberculosis (TB). In congruence with our investigations, we delineated the impact of Berg on T cells, wherein it enhanced adaptive memory responses by modulating key transcription factors, STAT4 and Akt. We translated this finding into the vaccine model of TB and observed a notable reduction in the burden of Mycobacterium tuberculosis (M.tb) in BCG-Berg co-immunized mice as compared to BCG vaccination. Moreover, Berg, along with BCG, also aided in a heightened proinflammatory response milieu that corroborates the host protective immune response against TB. Furthermore, this response aligns with the escalated central and resident memory responses by modulating the Akt-Foxo-Stat4 axis, which plays a crucial role in enhancing the vaccine efficacy of BCG. These findings showcase the utilization of immunomodulator Berg as an immunoprophylactic agent to upgrade immunological memory, making it a more effective defender against TB.

Systemic Administration of Cowpea Mosaic Virus Demonstrates Broad Protection Against Metastatic Cancers.

The key challenge in cancer treatment is prevention of metastatic disease which is therapeutically resistant and carries poor prognoses necessitating efficacious prophylactic approaches that prevent metastasis and recurrence. It is previously demonstrated that cowpea mosaic virus (CPMV) induces durable antitumor responses when used in situ, i.e., intratumoral injection. As a new direction, it is showed that CPMV demonstrates widespread effectiveness as an immunoprophylactic agent - potent efficacy is demonstrated in four metastatic models of colon, ovarian, melanoma, and breast cancer. Systemic administration of CPMV stimulates the innate immune system, enabling attack of cancer cells; processing of the cancer cells and associated antigens leads to systemic, durable, and adaptive antitumor immunity. Overall, CPMV demonstrated broad efficacy as an immunoprophylactic agent in the rejection of metastatic cancer.

Cholecalciferol as a means of nonspecific immunoprophylaxis against COVID-19

The current direction of scientific research in recent years has been the study of the immunobiological properties of vitamin D. The purpose of this work was to analyze the results of oral administration of cholecalciferol in order to prevent infection with the SARS-CoV-2 virus in the first wave of the COVID-19 pandemic. The study was performed in the period from October 07 to December 29, 2020, when there were no immunobiological drugs for specific prevention of COVID-19. The total number of respondents was 73 people; all had been ill with coronavirus only once. The etiological diagnosis of the disease included molecular genetic testing of samples of two localizations obtained by the conventional method (nasopharynx, oropharynx). The concentration of antibodies to the virus was determined on average 2 months after the disease using a set of reagents SARS-CoV-2-IgG quantitative-ELISA-Best (JSC Vector-Best, Russia). An approximate assessment of IgM concentration was carried out using a set of SARS-CoV-2-IgM-ELISA-Best from the same manufacturer. Among the study participants were those who used immunobiological drugs for the prevention of infection (riamilovir, umifenovir hydrochloride monohydrate, human recombinant interferon alpha-2b, zinc acetate, vitamin C). In particular, 28 people (38.4%) took cholecalciferol (group No. 1) and 45 people (61.6%) did not use this (group No. 2). Statistical processing of the obtained data was performed using the statistical package STATISTICA v.12.5.192.5 (StatSoft, Inc., USA). We applied the analysis of basic statistics, Linear Discriminant Analysis, Kolmogorov–Smirnov test, Chi-Square test, Wald–Wolfowitz Runs Test, Kruskal– Wallis test. Differences in the incidence of respiratory distress syndrome of the two studied groups were revealed: in patients taking cholecalciferol, the syndrome did not develop at all; in group No. 2, it was registered in 20.0% of cases (Chi-Square = 5.242, p = 0.02). In addition, in patients of group No. 1, the concentration of IgG 2 months after the disease was 3.8 times higher than the values in group No. 2 (Chi-Square = 9.268, p = 0.003). Similar differences were found for the IgM level (Wilks' Lambda: 0.659 approx. F (7.32) = 2.367 p < 0.045). It was known that in both groups there were respondents who used other immuno-active substances for preventive purposes. In the first group there were 18 people (24.7% of all); in the second, there were 13 people (17.8% of all). It was found that those who used other immuno-active substances and did not take vitamin D suffered the disease more easily than everyone else. The respondents who did not use any immunoprophylactic agents were the next in terms of the severity of the infection. The respondents who took cholecalciferol mainly assessed the severity of the infection as average. The study participants who took both vitamin D and used other means of prevention suffered the most from COVID-19. Respondents who took cholecalciferol more often than others reported long-term fatigue, exacerbation of chronic and the appearance of new diseases (hypertension, cardialgia, bronchial asthma, allergies, decreased visual acuity), muscle, joint and vertebral pains that appeared for the first time. The phenomenon of arthralgia and other lesions of large joints in COVID-19 was described by us earlier. Studies by other authors also report frequent complaints of increased fatigue and joint pain. At the same time, the role of vitamin D is considered exclusively from the standpoint of vitamin deficiency in a new coronavirus infection and its potential role in inhibiting hyperinflammatory reactions, as well as accelerating the healing process of affected areas, especially in lung tissue. It was found that vitamin D intake did not affect the incidence of fever, the incidence of pneumonia, the volume of lung tissue damage (based on computed tomography data), the duration of hospitalization and the disease as a whole, and also did not prevent the development of anosmia and dysgeusia. The use of vitamin D as a protective agent to prevent infection with the SARS-CoV-2 virus has had an impact on reducing the frequency/ prevention of cases of respiratory distress syndrome during the disease. Also, those who took vitamin D recorded an increase in the formation of IgG to the SARS-CoV-2 virus 2 months after infection 3.8 times higher than the values recorded in respondents who did not take cholecalciferol. The participants who took cholecalciferol suffered the infection more severely, especially if they used any other protective substances. Also, with the preventive intake of vitamin D after COVID-19, increased fatigue persisted longer, the appearance of new and activation of chronic diseases and muscle, joint and vertebral pains that appeared for the first time were reported more often, which correlates with the data we received earlier.

Острые, рекуррентные и рецидивирующие инфекции респираторного тракта у детей: вопросы иммунопрофилактики и иммунотерапии

The article is focused on the issues of immunoprophylaxis and immunotherapy of acute, recurrent and repeat respiratory infections in children. The authors underscore the high efficacy of active specific immunoprophylaxis against influenza virus, pneumococcal and Hib-infections. They emphasize that the use of combined immunoprophylaxis (vaccine + non-specific immunoprophylactic agents) is effective for achieving the maximal preventive effect, especially in children with recurrent and repeat respiratory infections. The article elucidates such issues as the mode of action and the efficacy of therapy and prevention, as well as the tolerability and safety of topical bacterial lysates in pediatric practice. It also reviews the pathogenetic rationale of using topical bacterial lysate IRS 19 in the prevention and treatment of acute, recurrent and repeat respiratory infections in children. The authors highlight the beneficial therapeutic effects of topical bacterial lysate Imudon on the clinical course of infectious and inflammatory oropharyngeal diseases and its preventive action. The authors outline the good tolerability of topical bacterial lysates used in pediatric practice. Taking into consideration that achievement of the most effective prevention of acute respiratory infections (ARI) in children with recurrent and repeat respiratory infections is possible via combination of immunizations, whereas topical bacterial lysates can be applied successfully as non-specific immunoprophylactic agents. KEYWORDS: vaccination, influenza, children, immunity, immunotherapy, immunoprophylaxis, acute respiratory infections, recurrent respiratory infections, repeat respiratory infections, topical bacterial lysates, trained immunity, frequently ill children. FOR CITATION: Zaplatnikov A.L., Girina A.A., Burtseva E.I. et al. Acute, recurrent and repeat respiratory infections in children: the issues of immunoprophylaxis and immunotherapy. Russian Journal of Woman and Child Health. 2023;6(1):50–59 (in Russ.). DOI: 10.32364/2618- 8430-2023-6-1-50-59.

Перспективные иммуномодулирующие эффекты бактериальных лизатов в профилактике и лечении острых и реккурентных респираторных инфекций у детей

The incidence of influenza and acute respiratory infections (ARI) continues to grow, including due to limited opportunities for immunoprophylaxis of the most common respiratory infections, in particular, acute respiratory viral infections (ARVI). Attempts are being made to reduce the children susceptibility to respiratory pathogens through the rational use of nonspecific immunoprophylactic agents, among which bacterial lysates (BL) occupy a special place. BL key patterns, contributing to the prevention of viral infections, are innate immune response activation, excessive inflammatory response prevention, adaptive immune response stimulation. BL contain fragments of inactivated various pathogenic bacteria strains that are important in the ARI etiology. Obtaining lysates of bacterial strains is possible by mechanical or chemical lysis. The article discusses the results of preclinical and clinical studies on BL, as well as suggests the expediency of further study concerning the BL pharmacodynamic effects within the modern concept of trained immunity. The authors conclude that BL as a trained immunity inducer according to the rationally selected regimen can contribute to the respiratory infections' prevention both during COVID-19 pandemic and post-pandemic period. KEYWORDS: acute respiratory infections, acute respiratory viral infections, influenza, trained immunity, immunoprophylaxis, bacterial lysate. FOR CITATION: Zaplatnikov A.L., Kanner E.V., Kanner I.D., Girina A.A., Farber I.M., Maximov M.L. Promising immunomodulatory effects of bacterial lysates in the prevention and treatment of acute and recurrent respiratory infections in children. Russian Journal of Woman and Child Health. 2023;6(3):290–297 (in Russ.). DOI: 10.32364/2618-8430-2023-6-3-12.

Субъединичные бактерийные вакцины в ветеринарии

Periodic spontaneous emergence of more virulent strains of pathogens, environmental changes, socio-economic factors, as well as an increase in the level of contacts between different regions are the main reasons for the emergence of new infectious diseases, including zoonotic ones. The main objective of preventive measures aimed at preventing the occurrence of diseases that cause large financial losses to farms is to carry out mass vaccination of livestock against relevant infections. A reasonable choice of a vaccine preparation is an important link in solving this problem. The use of live vaccines carries the potential risk of recombination of the vaccine strain with the field strain, in addition, their use is not always allowed by the rules for importing products of animal origin. As a safe alternative, subunit vaccines, which contain only specific fragments (subunits) of the virus or bacteria capable of being recognized by the animal's immune system, are increasingly being used in animal husbandry. Despite the biotechnological difficulties in obtaining subunit vaccines, the relevance of the scientific direction and the great potential of this type of biological preparations are noted. With the advent of recombinant technologies, the creation of subunit vaccines has become more active, but the main focus is on the production of viral vaccines. This is because bacterial subunit vaccines are more difficult to develop because the bacterial genome is more complex, leading to a lengthy and laborious screening process. This article presents an analysis of literature data, scientific articles and reviews of foreign and domestic researchers, which forms a modern idea of the prospects for the use of subunit bacterial vaccines in the field of veterinary medicine. A brief description of the ongoing experiments is given and an assessment of their effectiveness based on the conclusions of the researchers is put forward. A special place is occupied by the comparative characteristics of the technology for obtaining viral and bacterial subunit vaccines, which makes it possible to put forward a position on further prospects in the development of immunoprophylactic agents.

Validating Immunomodulatory Responses of r-LdODC Protein and Its Derived HLA-DRB1 Restricted Epitopes against Visceral Leishmaniasis in BALB/c Mice.

Vaccination is considered the most appropriate way to control visceral leishmaniasis (VL). With this background, the r-LdODC protein as well as its derived HLA-DRB1-restricted synthetic peptides (P1: RLMPSAHAI, P2: LLDQYQIHL, P3: GLYHSFNCI, P4: AVLEVLSAL, and P5: RLPASPAAL) were validated in BALB/c mice against visceral leishmaniasis. The study was initiated by immunization of the r-LdODC protein as well as its derived peptides cocktail with adjuvants (r-CD2 and MPL-A) in different mice groups, separately. Splenocytes isolated from the challenged and differentially immunized mice group exhibited significantly higher IFN-γ secretion, which was evidenced by the increase in the expression profile of intracellular CD4+IFN-γ T cells. However, the IL-10 secretion did not show a significant increase against the protein and peptide cocktail. Subsequently, the study confirmed the ability of peptides as immunoprophylactic agents, as the IE-I/AD-I molecule overexpressed on monocytes and macrophages of the challenged mice group. The parasitic load in macrophages of the protein and peptides cocktail immunized mice groups, and T cell proliferation rate, further established immunoprophylactic efficacy of the r-LdODC protein and peptide cocktail. This study suggests that the r-LdODC protein, as well as its derived HLA-DRB1-restricted synthetic peptides, have immunoprophylactic potential and can activate other immune cells' functions towards protection against visceral leishmaniasis. However, a detailed study in a humanized mice model can explore its potential as a vaccine candidate.

On the relationship between anosmia/dysgeusia and nonspecific immunoprophylaxis COVID-19

The issues of non-specific immunoprophylaxis in the patients with new coronavirus infection have been raised since the WHO announced the COVID-19 pandemic. According to numerous studies, the new coronavirus infection is accompanied by manifestations of anosmia and dysgeusia. The purpose of this study was to perform a retrospective study of the relationships between nonspecific immunoprophylaxis of COVID-19 and conditions of anosmia/dysgeusia in the persons who underwent this infection in Sverdlovsk region over 2020.
 We have studied clinical and laboratory data of 84 employees at the general medical institution providing emergency pediatric care. All participants suffered a single infection caused by SARS-CoV-2. Etiological diagnostics included mandatory virological PCR testing of biological samples. The concentration of antibodies to the virus was determined using a set of reagents for SARS-CoV-2-IgG detection (JSC Vector-Best, Novosibirsk, Russia). A sufficient part of this group (n = 41; 48.8% of total sample) reported self-administration of non-specific immunoprophylactic therapy of COVID-19 (without consulting a doctor) since the beginning of coronavirus pandemics. To this purpose, cholecalciferol, riamilovir, human recombinant IFNa-2b, umifenovir hydrochloride monohydrate, ascorbic acid, zinc acetate were used. In 58 cases (69% of total), clinical course of infection was complicated by loss of taste and sense of smell (group No. 1), in 26 people (31.0%), no changes in taste and sense of smell were detected (group No. 2). Statistical evaluation of the data was performed using STATISTICA v.12.5.192.5 package (StatSoft, Inc., USA). Along with basic statistics, cluster analysis was performed.
 The use of cluster analysis allowed us to establish that there is a connection between the incidence of anosmia/dysgeusia and usage of distinct immunoprophylactic agents. In particular, the use of human recombinant IFNa-2b is protective in terms of reducing the number complications in COVID-19, especially, anosmia/dysgeusia caused by the new coronavirus. The use of this drug was associated with 8.5-fold decrease in the number of complications by (p = 0.03). Moreover, invasive intranasal usage of interferon, was associated with decreased hospitalization terms by 14.3% (p = 0.01); lower volume of lung tissue damage (p = 0.03), higher concentrations of IgG to SARS-CoV-2 at 2 months after reconvalescence (p = 0.001).
 For the first time, data were presented on the relationship between usage of immunoprophylactic agents and manifestations of anosmia/dysgeusia in COVID-19. The protective role of human recombinant IFNa-2b has been shown in terms of reduced incidence of the disease complications, e.g., anosmia/dysgeusia, degree of lung damage, as well as development of an antiviral humoral immune response. The data obtained could be used to substantiate clinical recommendations for prevention of new outbreaks of coronavirus infection. The limitation of the obtained results is small number of cases, thus requiring additional studies in a wider sample of respondents.

Arthralgia and other pathologies of large joints as a consequence of a new coronavirus infection (COVID-19)

Introduction. Coronavirus disease 2019 is a new pandemic caused by severe acute respiratory distress-coronavirus 2. This virus mainly affects the respiratory system, but can also affect other organ systems, including musculoskeletal. In the scientific literature, there are data on pathological changes in the joints as one of the symptoms of long-term Covid-19. The aim of the work was a retrospective analysis of cases of arthralgia and severe lesions of large joints and spine as long-term complications of Covid-19. Materials and methods. Data collection was carried out in two stages after the acute Covid-19 was stopped: after 2 months (72 people, group №1) and after 2 years (700 people, group №2), the cohorts of the subjects did not overlap. Some of the respondents in group №1 complained of pain in the joints and spine (29 people, group №1B), the rest had no pain (43 people, group №1A). Clinical, instrumental and laboratory data (including IgG) were studied in all of them and questionnaire data were obtained. The questionnaires included questions about anthropometric data, the nature of the course of the disease, complications and other information. To evaluate the results, cluster analysis was used, basic statistics were determined, Chi-Square test was performed (program Statistica v.12.5.192.5, StatSoft, Inc., USA). Results. It was found that the gender, height, weight, age of the patient, body mass index cannot be associated with the occurrence of joint/muscle pain. Among the factors that correlated with arthralgia were: pulmonary insufficiency (p=0,03), the volume of lung tissue damage (p=0,02), the use of nonspecific immunoprophylactic agents, in particular umifenovir hydrochloride monohydrate (p=0,04), the use of antiviral agents in the treatment, in particular, vitaglutam (p=0,04). In addition, respondents who experienced pain in the joints and spine were significantly more likely (1,8 times) to complain of fatigue (p=0,02). The second stage — evaluation of the results of the examination of patients in group №2 — showed that Covid-19 resulted in a 3-4-fold increase in cases of primary detection of bilateral aseptic necrosis of the femoral head in young (up to 40 years old) patients. Discussion. The results of the study further confirm that pathological changes in the joints should be considered as one of the typical signs of postcovid syndrome. It can be argued that among the numerous parameters studied, there is no one that would uniquely determine the development of articular pathology. In general, there is a group of conditions that may be associated with arthralgia. These include: the use of non specific immunoprophylaxis, pneumonia and taking antiviral drugs during treatment. Conclusion. Thus, the presence of transient arthralgias and, to a lesser extent, more severe joint pathologies can be considered as one of the manifestations of postcovid syndrome. It cannot be excluded that immunoactive substances used for the prevention and treatment of a new coronavirus infection may be associated with a pathological process in the joints. In general, the pathogenesis of Covid-19 complications currently needs further study to be deciphered. From the point of view of practical application of the data obtained, it is important that the occurrence of arthralgia is associated with complaints of increased fatigue after Covid-19, which should suggest the need for additional examination of such patients as a preventive measure in the development of an irreversible process in large joints.

Development of Novel Immunoprophylactic Agents against Multidrug-Resistant Gram-Negative Bacterial Infections.

The widespread emergence of antibiotic resistance, including multidrug resistance in Gram-negative (G-) bacterial pathogens, poses a critical challenge to the current antimicrobial armamentarium. Antibody-drug conjugates (ADCs), primarily used in anticancer therapy, offer a promising treatment alternative due to their ability to deliver a therapeutic molecule while simultaneously activating the host immune response. The Cloudbreak platform is being used to develop ADCs to treat infectious diseases, composed of a therapeutic targeting moiety (TM) attached via a noncleavable linker to an effector moiety (EM) to treat infectious diseases. In this proof-of-concept study, 21 novel dimeric peptidic molecules (TMs) were evaluated for activity against a screening panel of G- pathogens. The activities of the TMs were not impacted by existing drug resistance. Potent TMs were conjugated to the Fc fragment of human IgG1 (EM), resulting in 4 novel ADCs. These ADCs were evaluated for immunoprophylactic efficacy in a neutropenic mouse model of deep thigh infection. In colistin-sensitive infections, 3 of the 4 ADCs offered protection similar to that of therapeutically dosed colistin, while CTC-171 offered enhanced protection. The efficacy of these ADCs was unchanged in colistin-resistant infections. Together, these results indicate that the ADCs used here are capable of potent binding to G- pathogens regardless of lipopolysaccharide (LPS) modifications that otherwise lead to antibiotic resistance and support further exploration of ADCs in the treatment of infections caused by drug-resistant G- bacteria.

Immunostimulatory role of rBmHSP60 from filarial parasite Brugia malayi

Objective: To evaluate the immunostimulatory potential of cross-reactive molecule heat shock protein 60 (HSP60) of filarial parasite Brugia malayi and Leishmania donovani. Methods: HSP60 of Brugia malayi (BmHSP60) was amplified using gene-specific primer, cloned in pTriEx4 vector, expressed in BL21-DE3 cells, and recombinant HSP60 (rHSP60) of ~65 kDa was purified by affinity chromatography using Ni-NTA column. The recombinant protein was desalted by the dialysis membrane, and the presence of endotoxin level was determined by Limulus amebocyte lysate assay. The recombinant protein was tested for cell proliferation, nitric oxide release, expression of Th1 and Th2 cytokines, and transcription factors (STATs) in vitro using murine macrophage cell line (J774A.1). Results: Higher cell proliferation indicated that BmHSP60 had immunostimulatory potential. rBmHSP60 exposure upregulated the expression of iNOS, STAT1, STAT4, Th1 cytokines (IFN–γ, TNF–α, IL-12), and nitric oxide release. In addition, no remarkable change was observed in the expression of IL-6, IL-10, and STAT3 in macrophage cell line J774A.1. The ELISA analysis showed the levels of IFN-γ, TNF-α, and IL-12 were upregulated while IL-10 level was downregulated, revealing that BmHSP60 triggered a Th1 immune response. Conclusions: Our study demonstrates that rBmHSP60 has immunogenic properties which effectively enhances the Th1 type immune responses, and can be used as an immunoprophylactic agent against leishmaniasis. Furthermore, in vivo studies are in progress to determine the protective role of rBmHSP60 against Leishmania donovani infection in a mouse model.

The State of Affairs in Post-Exposure Leprosy Prevention: A Descriptive Meta-Analysis on Immuno- and Chemo-Prophylaxis.

ObjectiveAnnually, over 200,000 people are diagnosed with leprosy, also called Hansen’s disease. This number has been relatively stable over the past years. Progress has been made in the fields of chemoprophylaxis and immunoprophylaxis to prevent leprosy, with a primary focus on close contacts of patients. In this descriptive meta-analysis, we summarize the evidence and identify knowledge gaps regarding post-exposure prophylaxis against leprosy.MethodsA systematic literature search according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology was conducted by searching the medical scientific databases Cochrane, Embase, Pubmed/MEDLINE, Research Gate, Scopus and Web of Science on Jan. 22, 2020, using a combination of synonyms for index terms in four languages: “leprosy” and “population” or “contacts” and “prevention” or “prophylaxis.” Subsequently, Infolep.org and Google Scholar were searched and the "snowball method" was used to retrieve other potentially relevant literature. The found articles were screened for eligibility using predetermined inclusion and exclusion criteria.ResultsAfter deduplication, 1,515 articles were screened, and 125 articles were included in this descriptive meta-analysis. Immunoprophylaxis by bacillus Calmette-Guérin (BCG) vaccination is known to provide protection against leprosy. The protection it offers is higher in household contacts of leprosy patients compared with the general population and is seen to decline over time. Contact follow-up screening is important in the first period after BCG administration, as a substantial number of new leprosy patients presents three months post-vaccination. Evidence for the benefit of re-vaccination is conflicting. The World Health Organization (WHO) included BCG in its Guidelines for the Diagnosis, Treatment and Prevention of Leprosy by stating that BCG at birth should be maintained in at least all leprosy high-burden regions. Literature shows that several vaccination interventions with other immunoprophylactic agents demonstrate similar or slightly less efficacy in leprosy risk reduction compared with BCG. However, most of these studies do not exclusively focus on post-exposure prophylaxis. Two vaccines are considered future candidates for leprosy prophylaxis: Mycobacterium indicus pranii (MiP) and LepVax. For chemoprophylaxis, trials were performed with dapsone/acedapsone, rifampicin, and ROM, a combination of rifampicin, ofloxacin, and minocycline. Single-dose rifampicin is favored as post-exposure prophylaxis, abbreviated as SDR-PEP. It demonstrated a protective effect of 57% in the first two years after administration to contacts of leprosy patients. It is inexpensive, and adverse events are rare. The risk of SDR-PEP inducing rifampicin resistance is considered negligible, but continuous monitoring in accordance with WHO policies should be encouraged. The integration of contact screening and SDR-PEP administration into different leprosy control programs was found to be feasible and well accepted. Since 2018, SDR-PEP is included in the WHO Guidelines for the Diagnosis, Treatment and Prevention of Leprosy.ConclusionProgress has been made in the areas of chemoprophylaxis and immunoprophylaxis to prevent leprosy in contacts of patients. Investing in vaccine studies, like LepVax and MiP, and increasing harmonization between tuberculosis (TB) and leprosy research groups is important. SDR-PEP is promising as a chemoprophylactic agent, and further implementation should be promoted. More chemoprophylaxis research is needed on: enhanced medication regimens; interventions in varying (epidemiological) settings, including focal mass drug administration (fMDA); specific approaches per contact type; combinations with screening variations and field-friendly rapid tests, if available in the future; community and health staff education; ongoing antibiotic resistance surveillance; and administering chemoprophylaxis with SDR-PEP prior to BCG administration. Additionally, both leprosy prophylactic drug registration nationally and prophylactic drug availability globally at low or no cost are important for the implementation and further upscaling of preventive measures against leprosy, such as SDR-PEP and new vaccines.

Immune Dysregulation in Children With Down Syndrome.

Down syndrome (DS) is the most common genetic syndrome associated with immune defects. The extent of immune dysregulation in DS is substantial, spanning the innate and adaptive systems and including anomalies in: T and B cells, monocytes, neutrophil chemotaxis, circulating cytokines, and suboptimal antibody responses which all contribute to an increased risk of infections, poorer clinical outcomes and chronic inflammation in this vulnerable cohort. Other aspects of innate immunity may also be abnormal and contribute to the increased morbidity and warrant further interrogation such as: gamma delta T cell function, the inflammasome, Toll-like receptors and their pathways. Pharmacotherapies such as pavilizumab, pneumococcal and influenza immunizations, as well as potential immunoprophylactic agents such as pidotimod, azithromycin and Broncho-Vaxom may help alleviate the infectious consequences. Children with DS need to be managed with a heightened sense of awareness and urgency in the setting of sepsis and signs of chronic inflammation need regular screening and appropriate follow up.

PROTECTIVE EFFICACY OF A COMPLEX BIOPREPARATION BASED ON A SOMATIC EXTRACT OF TRICHINELLA AND IMUNOFAN IN EXPERIMENTAL TRICHINOSIS IN WHITE MICE

The purpose of this placebo-controlled randomized laboratory study was to evaluate the effectiveness of a complex biological product based on the Trichinella somatic antigen (SET) at a dose of 40 μg / mouse and an immunostimulant immunofan at a dose of 1 mg / mouse for T. spiralis larvae with experimental infection with them 40 days after the last injection of drugs. The preparations were administered twice, intramuscularly in 0.2 ml of sterile saline with an interval of 48 hours to 20 animals from 2 therapeutic groups. 10 mice of the control group received a placebo. Mice were experimentally infected with T. spiralis larvae at a dose of 30 ± 5 larvae / mouse orally. After 40-45 days, a control assessment was performed to detect T. spiralislarvae. The number of larvae of the parasite in animals treated with the complex drug was reduced by 61.98%, and in mice treated with an immunostimulant - by 31.42% (calculated from the geometric mean). The largest number of Trichinella larvae was found in the control group that received placebo.According to the results of the study, a conclusion was drawn about the effectiveness of double administration of a complex immunopreparation based on SET-40 and Imunofan, as well as on the prospects and feasibility of continuing further research in search of the most promising immunoprophylactic agents, their doses and frequency of use for trichinosis.

Visceral leishmaniasis: A novel nuclear envelope protein ‘nucleoporins-93 (NUP-93)’ from Leishmania donovani prompts macrophage signaling for T-cell activation towards host protective immune response

The shift of macrophage and T-cell repertoires towards proinflammatory cytokine signalling ensures the generation of host-protective machinery that is otherwise compromised in cases of the intracellular Leishmania parasite. Different groups have attempted to restore host protective immunity. These vaccine candidates showed good responses and protective effects in murine models, but they generally failed during human trials. In the present study, we evaluated the effect of 97 kDa recombinant nucleoporin-93 of Leishmania donovani (rLd-NUP93) on mononuclear cells in healthy and treated visceral leishmaniasis (VL) patients and on THP-1 cell lines. rLd-NUP93 stimulation increased the expression of the early lymphocyte activation marker CD69 on CD4+ and CD8+ T cells. The expression of the host protective pro-inflammatory cytokines IFN-γ, IL-12 and TNF-α was increased, with a corresponding down-regulation of IL-10 and TGF-β upon rLd-NUP93 stimulation. This immune polarization resulted in the up-regulation of NF-κB p50 with scant expression of SMAD-4. Augmenting lymphocyte proliferation upon priming with rLd-NUP93 ensured its potential for activation and generation of strong T-cell mediated immune responses. This stimulation extended the leishmanicidal activity of macrophages by releasing high amounts of reactive oxygen species (ROS). Further, the leishmanicidal activity of macrophages was intensified by the elevated production of nitric oxide (NO). The fact that this antigen was earlier reported in circulating immune complexes of VL patients highlights its antigenic importance. In addition, in silico analysis suggested the presence of MHC class I and II-restricted epitopes that proficiently trigger CD8+ and CD4+ T-cells, respectively. This study reported that rLd-NUP93 was an effective immunoprophylactic agent that can be explored in future vaccine design.

Co-factor-independent phosphoglycerate mutase of Leishmania donovani modulates macrophage signalling and promotes T-cell repertoires bearing epitopes for both MHC-I and MHC-II.

Immunoactivation depends upon the antigen potential to modulate T-cell repertoires. The present study has enumerated the effect of 61 kDa recombinant Leishmania donovani co-factor-independent phosphoglycerate mutase (rLd-iPGAM) on mononuclear cells of healthy and treated visceral leishmaniasis subjects as well as on THP-1 cell line. rLd-iPGAM stimulation induced higher expression of interleukin-1β (IL-1β) in the phagocytic cell, its receptor and CD69 on T-cell subsets. These cellular activations resulted in upregulation of host-protective cytokines IL-2, IL-12, IL-17, tumour necrosis factor-α and interferon-γ, and downregulation of IL-4, IL-10 and tumour growth factor-β. This immune polarization was also evidenced by upregulation of nuclear factor-κ light-chain enhancer of activated B cells p50 and regulated expression of suppressor of mother against decapentaplegic protein-4. rLd-iPGAM stimulation also promoted lymphocyte proliferation and boosted the leishmaniacidal activity of macrophages by upregulating reactive oxygen species. It also induced 1·8-fold higher release of nitric oxide (NO) by promoting the transcription of inducible nitric oxide synthase gene. Besides, in silico analysis suggested the presence of major histocompatibility complex class I and II restricted epitopes, which can proficiently trigger CD8+ and CD4+ cells, respectively. This study reports rLd-iPGAM as an effective immunoprophylactic agent, which can be used in future vaccine design.

Identification of Immunoreactive Polypeptides inHaemonchus contortusby Immunoprecipitation during Prepatent Infection in Sheep

In the current study immunoreactive polypeptides in Adult Somatic Extract (ASE), Excretory Secretory Product (ESP) and Larval Somatic Extract (LSE) of L3 stage were identified by employing immunoprecipitation, a lesser utilized technique on helminth parasites. Prepatent polyclonal sera were used to capture polypeptides in immunoprecipitation. Polypeptides eluted from the immune complex in ASE in SDS-PAGE were 26, 60, 120 & 170 kDa whereas in ESP these were 26, 32, 60 and 120 kDa showing absence of 170 kDa and presence of 32 kDa in ESP. In LSE the polypeptides captured were 26, 32, 60 & 120 kDa. Possible functional significance of the peptides in different antigens has been discussed and development of an immunoprophylactic agent has been speculated.

DNA-Based Influenza Vaccines as Immunoprophylactic Agents Toward Universality

Influenza is an illness of global public health concern. Influenza viruses have been responsible for several pandemics affecting humans. Current influenza vaccines have proved satisfactory safety; however, they have limitations and do not provide protection against unexpected emerging influenza virus strains. Therefore, there is an urgent need for alternative approaches to conventional influenza vaccines. The development of universal influenza vaccines will help alleviate the severity of influenza pandemics. Influenza DNA vaccines have been the subject of many studies over the past decades due to their ability to induce broad-based protective immune responses in various animal models. The present review highlights the recent advances in influenza DNA vaccine research and its potential as an affordable universal influenza vaccine.