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Context: Rabies is a fatal zoonotic disease that is endemic in India. Both forms of rabies, namely, encephalitic and furious, invariably lead to coma and death. Lack of awareness is the most critical barrier in accessing timely post-exposure prophylaxis that can prevent the progression to clinical disease. Aims: To report the case series of fourteen clinically suspected rabies cases. Settings and Design: We followed a retrospective study design. Data were collected from the Anti Rabies Section of Government Medical College, Jammu, which is a tertiary care hospital of Jammu Division. Methods and Material: We collected data of all patients over a period of three years, from 2017 to 2020, who were diagnosed as cases of clinically suspected rabies on the basis of classic signs and symptoms and who finally succumbed to the disease. Statistical Analysis Used: Descriptive statistics was used to describe the results of the study Results: In the present description, the mean age of the patients was 31 ± 18.6 years. Out of 14 suspected cases, 9 had not received any post-exposure prophylaxis—neither vaccine nor serum—and instead visited spiritual faith healers. The remaining patients had history of either incomplete, unknown, or incorrect vaccination status. Median duration of presentation of symptoms after dog bite was 42 days, with a range of 15–180 days. Mean survival of patients after presentation of symptoms was around 1.8 days Conclusions: Low level of awareness resulted in non-seeking of health-care services after animal bites.

Searching for a preparation that would meet all the requirements for modern adjuvants remains a matter of critical importance for specific immunoprophylaxis. Much information is available now on chitosan positive effect, including its effect on the immune response. The article provides results of the preclinical tests for different affordable chitosan-based products. For the test purposes, we took the following three products manufactured by LLC Bioprogress (Shchelkovo, Russia): water-soluble chitosan (succinate) – 2% solution edible chitosan (water-soluble) – 2% solution; edible chitosan (acid-soluble) – 2% solution, as well as antirabies vaccine RABIKOV manufactured by Shchelkovo Biocombinat (Russia). Immunogenic properties of chitosan-based products were tested in 85–100-day-old female white laboratory mice weighing 21–35 g. The animals were divided into 37 groups (6 mice in each group). Chitosan-based products were administered subcutaneously or intramuscularly, either together with the anti-rabies vaccine or without it. Animals from the control groups received either saline solution or the vaccine only. There was also a group of intact animals. The experiment demonstrated that the water-soluble chitosan (succinate) administered subcutaneously, acid-soluble edible chitosan (at a concentration of 1:64 and more), and water-soluble edible chitosan (at a concentration of 1:108) administered subcutaneously and intramuscularly increase the level of post-vaccination anti-rabies antibodies. Thus, the tested chitosan-based products do not have any negative impact on the laboratory animals and have immunogenic properties.

Dog bite injuries often present to Emergency Departments (ED), and between 2001 and 2003, approximately 4.5 million adults and children were injured. Injuries may range from puncture wounds to deep tissue lacerations or avulsions. Deaths have been described. Our objective was to describe dog bite injuries, the overall location of injuries, and need for vaccination among children who presented to a Pediatric ED designated as a level III trauma center with a robust facial surgical infrastructure. This was a 6-year retrospective study. Charts were identified by International Classification of Diseases, Tenth Revision (ICD-10) codes for lacerations or injuries secondary to animal bites and accessing the hospital's trauma database. Variables abstracted were age, sex, type of injury, location, need for antibiotics, immunization states and requirement of tetanus or rabies vaccine, disposition from ED to the operating room, home, or any in-patient unit. We excluded children older than 17 years of age and children who had a post-bite injury infection or injury not initially managed in our facility or medical system. The final cohort consisted of 152 children. The median age was 52 months and age ranged from 2 to 215 months. Children with a single bite injury were older when compared with those with numerous injuries, 81 and 62 months of age, respectively. Among young children, 75% of injuries occurred above the neck and 15.1% were managed in the operating room. Twenty-four percent of children required either a tetanus or rabies vaccination. Most dog bite injuries occurred to facial structures. Comprehensive care of dog victims included awareness of both dog and injured child vaccination status. [ABSTRACT FROM AUTHOR]

This study was a randomized, parallel-controlled of homologous vaccines with different immune procedure research to evaluate the immunogenicity and immune persistence of Zagreb 2-1-1 regimen of rabies vaccine in Chinese healthy individuals. 240 subjects aged ≤ 20、21-50、≥51 y were randomly divided into 2 groups (1:1), Zagreb 2-1-1 regimen receivers as experimental group and Essen 5 regimen receivers as controlled group. Researchers collected venous blood of each subject before vaccine injection and on the day 7, 14, 42, 180, 365 after first dose. The immunogenicity and immune persistence was assessed by neutralizing antibody. The positive rate of neutralizing antibody in experimental group was 14.53% on the 7th day, and raised to 100% on the 14th day. It showed no significant difference between experimental and controlled group (P>0.05). Either in experimental or controlled group, GMC of neutralizing antibody was up to the peak on the 14th day, and it showed no significant difference between two groups (P>0.05). On the 42nd day, the antibody positive rate remained 100% with both Zagreb 2-1-1 and Essen 5 regimens, and the GMC of antibodies also remained high level. Then, on the 180th and 365th day with both regimens, the GMC of antibodies dropped dramatically, although it remained above the protective level of 0.5 IU/ml, the positive rates dropped to 84.40% and 84.11% (on the 180th day), and 61.29% and 58.62% (on the 365th day). Rabies vaccine injected by Zagreb 2-1-1 regimen can produce neutralizing antibody fastly and perdurably.Registration: ClinicalTrials.gov #NCT01821911and NCT01827917

Rabies is a zoonotic single-stranded RNA lyssavirus that can cause acute infections of the central nervous system (CNS) including encephalomyelitis, encephalitis, and meningoencephalitis that is progressively fatal. Rabies is more common in developing countries, but approximately 23,000 people in the United States (US) are estimated to have been exposed or to have received post exposure prophylaxis (PEP) yearly. Nebraska Medicine follows the Advisory Committee on Immunization Practices (ACIP) guidelines for the vaccination series, as well as the 20 units/kg administration of immunoglobulin (RIG). Nebraska Medicine Medical Center (NMC) and Bellevue Medical Center (BMC) treat the scheduling of the complete rabies vaccine series differently. At both campuses, patients receive their immunoglobulin and first vaccine in the Emergency Department (ED). At NMC, patients are scheduled to receive the remainder of their vaccination series at the outpatient infusion center by the ED pharmacist. At BMC, the subsequent vaccinations are given as "Nurse Only" return visits to the ED. The objective of this study was to compare patient compliance of two different processes for follow-up rabies vaccine series completion. This project's primary aim was to determine the rate of patient compliance for follow up rabies vaccine doses. The secondary aims of this project were to determine if there was a difference in patient follow-up compliance between the two campuses, patient specific factors that impact compliance, and potential cost savings if a dose rounding protocol for RIG was utilized. This retrospective chart review was completed as a quality improvement project. Data from patients who had received either rabies immunoglobulin and/or a rabies vaccine, were >18 years of age, and were not admitted were collected for a 3-year period from July 1, 2019, to June 30, 2022. Data were abstracted from the patient's EMR (electronic medical records) using a SQL (Structured query language) query of pre-identified data elements. When unable to abstract with SQL query, data elements were manually abstracted. All data abstracted was collated and descriptive analysis performed. A total of 723 individual encounters were identified during the study period. After combining rabies series for each individual patient, 173 unique patients remained. After exclusions were applied, 143 patients were included: 104 patients from NMC, and 39 from BMC. For the primary outcome, appropriate completion between the two campuses was 78.3%. When comparing the two campuses, completion rates were higher at NMC (82% vs. 69%), although not statistically significant (p = 0.12). Appropriate completion of vaccine series was statistically significant for both payor and exposure type. Application of a dose rounding policy with those >45 kg, rounding to the nearest vial, as well as rounding down if at the midpoint interval, 56 fewer vials would have been used between the two campuses. This would have resulted in a potential cost savings of $57,928.64 over the study period. [ABSTRACT FROM AUTHOR]

Rabies, a viral disease spread by infected animal bites that causes encephalitis in humans and other mammals, is a neglected infectious disease present on all continents except Antarctica. Spain has been free of terrestrial rabies since 1978. However, due to its geographical situation, it represents a bridge for imported cases from an endemic continent such as Africa to Europe. Rabies vaccination in dogs is an essential preventive tool against this zoonosis. The aim of this study was to determine the state of the immune response against rabies virus in dogs in Spain and to demonstrate whether several factors that have been previously related to the influence of the seroprevalence of this species are involved here. The seroconversion level of this zoonotic virus was assessed in a total of 1060 animals. Indirect ELISA was used to obtain data for statistical analysis to evaluate the studied variables. Working under the concept of One Health, this study provides relevant information to be taken into consideration not only to prevent re-emergence in countries free of this disease but also for prevention and control in endemic countries. [ABSTRACT FROM AUTHOR]

Background: Rabies, a potentially lethal virus, affects more than 150 countries. Although the rabies vaccine and immunoglobulin have been available since 1908, Bangladesh is new to vaccine manufacturing. We checked the quality of the local manufacturing rabies vaccine for substandard. Methods: The potency and immunogenicity of 20 vaccines were analyzed by three in vivo and in vitro methods from March 2020 to May 2023. Single radial immunodiffusion, fluorescent antibody virus neutralization, and national institutes of health tests were carried out to evaluate the vaccine's efficacy to provide sufficient protection against the rabies virus. Results: The potency of the rabies vaccine was determined by the in vitro SRID method by measuring glycoprotein content. An average of 16 articles from each batch was calculated. The minimum and maximum average mean values of the 20 batches were 5.058 and 5.346, respectively. The variance was calculated at 0.00566. We found a coefficient of variation (CV) between 9.36% and 14.80%. The 100% sample was satisfactory, as these samples had a potency of over 2.5 IU/mL. To observe immunogenicity, we applied the FAVN method for determining antibody titers. An average of 16 articles from every batch were counted to quantify antibody titers. The mean quantity of antibody titers ranged from 2.389 to 3.3875. The CV was slightly lower because of the dispersion of the data. At last, we performed an in vivo method, the NIH test method, to determine potency based on mortality rate. We found a mean value of 4.777 IU/SHD with a standard deviation of 1.13 IU/SHD. All 20 batches were found 100% satisfactory in the NIH test. Conclusion: The study implies that the rabies human vaccines manufactured in Bangladesh are potent enough to provide sufficient immunogenicity. Our research is warranted testimony for healthcare providers who work to extirpate rabies. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the immunogenicity and safety of an anti-rabies monoclonal antibody (mAb), ormutivimab, compared with human rabies immunoglobulin (HRIG). Methods: This phase III trial was designed as a randomized, double-blind, non-inferiority clinical trial in patients aged ≥18 years with suspected World Health Organization category Ⅲ rabies exposure. The participants were randomized 1:1 to ormutivimab and HRIG groups. After thorough wound washing and injection of ormutivimab/HRIG on day 0, the vaccination was administered on days 0, 3, 7, 14, and 28. The primary endpoint was the adjusted geometric mean concentration (GMC) of rabies virus-neutralizing activity (RVNA) on day 7. The endpoint of safety included the occurrence of adverse reactions and serious adverse events. Results: A total of 720 participants were recruited. The adjusted-GMC of RVNA (0.41 IU/ml) on day 7 in ormutivimab group was not inferior to that in the HRIG group (0.41 IU/ml), with ratio of adjusted-GMC of 1.01 (95% confidence interval: 0.91, 1.14). The seroconversion rate of the ormutivimab group was higher than that of the HRIG group on days 7, 14, and 42. Most local injection sites and systemic adverse reactions reported from both groups were mild to moderate in severity. Conclusion: ormutivimab + vaccine can protect victims aged ≥18 years with category Ⅲ suspected rabies exposure as a component of postexposure prophylaxis. ormutivimab has a weaker influence on the immunity response of rabies vaccines. Clinical trials registration: ChiCTR1900021478 (the Chinese Clinical Trial Registry of World Health Organization).

Abstract Background To achieve well-regulated distribution, storage, and utilization of the rabies vaccine, health facilities should adhere to standard operating procedures. In Namibia, information on inventory management, utilization, monitoring, and reporting of rabies vaccine adherence to standard operating procedures in public healthcare facilities is insufficient. The aim of this study was to assess adherence to rabies vaccine standard operating procedures and inventory management and to compare rabies vaccine expenditure to the number of patients who received rabies vaccination at the Ministry of Health and Social Services’ public healthcare facilities from 2018 to 2020. Methods A cross-sectional, web-based questionnaire consisting of closed-ended questions was sent to 147 pharmacy staff and warehouse managers working in the 14 regions of Namibia during the period of May 1, 2021, to June 2, 2021. The overall expenditure and the total number of patients vaccinated from 2018 to 2020 were obtained from national-level logistic and vaccination program coordinators. Data were coded and transcribed into Microsoft® Excel® 2013 and analyzed using SPSS® version 27. Results One hundred and thirty-three completed questionnaires were received from sixty-nine public health centers and hospitals. The group of respondents consisted of pharmacist assistants (50%), pharmacy technicians (12%), pharmacists (36.8%), senior pharmacists (0.8%), and chief pharmacists (1.5%). Overall, adherence to standard operating procedures was poor (27.1%). Rabies vaccine distributed to public health facilities from 2018 to 2020 was worth N$75,381,419.91 (~ US$4,074,671.46) and was expected to vaccinate 87,269 patients; however, only 95 cases of both rabies and rabid dog-bite patients were reported. The major inventory management challenges for public healthcare facilities include an inadequate number of pharmacy staff, poor adherence to standardized pharmaceutical warehousing, lack of regular supervision, and inadequate staff training. Conclusion Inventory management practices in public healthcare facilities were not in compliance with standard operating procedures. There is a significant discrepancy between rabies vaccine expenditure and the number of patients that were vaccinated. Therefore, there is a need for adequate staff training on inventory management and regular facility supervision to enforce optimal rabies vaccine inventory management practices.

Abstract Background Rabies, a potentially lethal virus, affects more than 150 countries. Although the rabies vaccine and immunoglobulin have been available since 1908, Bangladesh is new to vaccine manufacturing. We checked the quality of the local manufacturing rabies vaccine for substandard. Methods The potency and immunogenicity of 20 vaccines were analyzed by three in vivo and in vitro methods from March 2020 to May 2023. Single radial immunodiffusion, fluorescent antibody virus neutralization, and national institutes of health tests were carried out to evaluate the vaccine's efficacy to provide sufficient protection against the rabies virus. Results The potency of the rabies vaccine was determined by the in vitro SRID method by measuring glycoprotein content. An average of 16 articles from each batch was calculated. The minimum and maximum average mean values of the 20 batches were 5.058 and 5.346, respectively. The variance was calculated at 0.00566. We found a coefficient of variation (CV) between 9.36% and 14.80%. The 100% sample was satisfactory, as these samples had a potency of over 2.5 IU/mL. To observe immunogenicity, we applied the FAVN method for determining antibody titers. An average of 16 articles from every batch were counted to quantify antibody titers. The mean quantity of antibody titers ranged from 2.389 to 3.3875. The CV was slightly lower because of the dispersion of the data. At last, we performed an in vivo method, the NIH test method, to determine potency based on mortality rate. We found a mean value of 4.777 IU/SHD with a standard deviation of 1.13 IU/SHD. All 20 batches were found 100% satisfactory in the NIH test. Conclusion The study implies that the rabies human vaccines manufactured in Bangladesh are potent enough to provide sufficient immunogenicity. Our research is warranted testimony for healthcare providers who work to extirpate rabies.

Vaccination is the most feasible way of preventing rabies, an ancient zoonosis that remains a major public health concern globally. However, administration of inactivated rabies vaccination without adjuvants is always inefficient and necessitates four to five injections. In the current study, we explored the adjuvant characteristics of cordycepin, a major bioactive component of Cordyceps militaris, to boost immune responses against a commercially available rabies vaccine. We found that cordycepin could stimulate stronger phenotypic and functional maturation of dendritic cells (DCs). For animal experiments, mice were immunized 3 times with rabies vaccine in the presence or absence of cordycepin at 1-week interval. Analysis of T cell differentiation and serum antibody isotypes showed that humoral immunity was dominant with a Th2 biased immune response. These results were also supported by the raised ratio of follicular helper T cells (TFH) and germinal center B cells (GCB). Thus, titer of rabies virus neutralizing antibody (RVNAb) and rabies virus-specific memory B cells were both raised as a result. Furthermore, administration of cordycepin did not cause pathological phenomena or body weight loss. The findings indicate that cordycepin could be used as a promising adjuvant for rabies vaccines to get a higher range of protection without any side effects.

• Quality of shelter management affects rabies vaccine success rate. • Poor management leads to vaccine failure rate of almost 50 %. • Keeping of individual health record and health check before vaccination is critical for vaccination success. Rabies vaccination is mandatory in dogs in Thailand. In this study, shelter management quality and rabies immune status were evaluated by questionnaire and rabies virus neutralising antibody (RVNA) measurement. The questionnaire was designed to assess all relevant factors of shelter management, which could impact the rabies vaccine antibody response. Thirteen participating shelters were classified into 4 groups, namely group A (best), B (good), C (fair), and D (require improvement). Sera were collected from randomly selected dogs (n = 113) within 4 weeks after rabies re-vaccination from a representative shelter of group B, C and D. Sample from group A was not included in the study due to time limitation. Both the number of dogs with acceptable response (RVNA ≥ 0.5 IU/ml) and the RVNA titres were significantly higher in group B than group C and D. Our results indicate that the quality of shelter management could affect rabies immune status. [ABSTRACT FROM AUTHOR]

Introduction: Rabies is a serious public health problem worldwide for which an effective treatment method is lacking but can be prevented by vaccines. Current vaccines are produced in cell or egg cultures, which are both costly and time consuming. Methods: Here, a non-replicating mRNA vaccine (RV021) encoding the rabies virus glycoprotein was developed in vitro, and its immunogenicity and protective efficacy against live virus was evaluated in mice. Results: A two-dose vaccination with 1 mg of RV021 at 7-day intervals induced a protective level of neutralizing antibody that was maintained for at least 260 days. RV021 induced a robust cellular immune response that was significantly superior to that of an inactivated vaccine. Two doses of 1 mg RV021 provided full protection against challenge with CVS of 30~60-fold lethal dose, 50%. Vaccine potency testing (according to the National Institutes of Health) in vivo revealed that the potency of RV021 at 15 mg/dose was 7.5 IU/dose, which is substantially higher than the standard for lot release of rabies vaccines for current human use. Conclusion: The mRNA vaccine RV021 induces a strong protective immune response in mice, providing a new and promising strategy for human rabies prevention and control. [ABSTRACT FROM AUTHOR]

Rabies is a fatal zoonotic disease caused by the rabies virus. Despite existing vaccines, failures still persist. Complete protection relies on improving vaccination for delayed antibody response and weak cellular immunity. A more effective and secure vaccine is necessary for rabies prevention. For this purpose, we employed the use of PIKA adjuvant, a stabilized double-stranded RNA that interacts with TLR3, as an enhancer for the rabies immunization. Testing on mice infected with seven rabies strains prevalent in China showed over 80% protective efficacy without immunoglobulin. In contrast, the PIKA rabies vaccine exhibited a more significant enhancement in neutralizing antibody levels just 5 days post-vaccination, surpassing the immune response induced by licensed rabies vaccines. Furthermore, the administration of the PIKA rabies vaccine resulted in a significant augmentation in the population of T cells that produce IFN-γ in response to the antigen. Additionally, elevated levels of IL-1β, IL-6, CCL-2, and TNF-α were observed at the injection site. Furthermore, an increase in the levels of chemotactic proteins and pro-inflammatory molecules in the serum was observed following administration of the PIKA rabies vaccine. Confirmation of the mechanism of action of PIKA was further established by testing it on TLR3-knockout mice, proving that its adjuvant function is dependent on the TLR3 pathway. Taken together, these results indicate that the PIKA vaccine for rabies shows potential as a highly efficacious approach, resulting in a significant enhancement of the efficacy of rabies vaccines. [ABSTRACT FROM AUTHOR]

This article discusses a study conducted in Bangladesh on the effectiveness of egg-based oral rabies vaccination programs in stray dogs. The study found that stray dogs showed a preference for egg-based baits and that these baits were more successful in vaccinating the dogs. However, the study also highlighted the importance of considering cultural preferences and safety when implementing such programs. It is important to note that the study has limitations, including subjective monitoring methods and variations in bait distribution methods. Readers are encouraged to refer to the Terms of Use for more information. [Extracted from the article]

Inoculation routes may significantly affect vaccine performance due to the local microenvironment, antigen localization and presentation, and, therefore, final immune responses. In this study, we conducted a head-to-head comparison of immune response and safety of inactivated rabies vaccine inoculated via intraperitoneal (IP), intramuscular (IM), subcutaneous (SC) and needle-free injection technology-based intradermal (ID) routes in ICR mice. Immune response was assessed in terms of antigen-specific antibodies, antibody subtypes and neutralizing antibodies for up to 28 weeks. A live rabies virus challenge was also carried out to evaluate vaccine potency. The dynamics of inflammatory cell infiltration at the skin and muscle levels were determined via histopathological examination. The kinetics and distribution of a model antigen were also determined by using in vivo fluorescence imaging. Evidence is presented that the vaccine inoculated via the ID route resulted in the highest antigen-specific antibody and neutralizing antibody titers among all administration routes, while IP and IM routes were comparable, followed by the SC route. Antibody subtype analysis shows that the IP route elicited a Th1-biased immune response, while SC and IM administration elicited a prominent Th2-type immune response. Unexpectedly, the ID route leads to a balanced Th1 and Th2 immune response. In addition, the ID route conferred effective protection against lethal challenge with 40 LD50 of the rabies CVS strain, which was followed by IP and IM routes. Moreover, a one-third dose of the vaccine inoculated via the ID route provided comparable or higher efficacy to a full dose of the vaccine via the other three routes. The superior performance of ID inoculation over other routes is related to longer local retention at injection sites and higher lymphatic drainage. Histopathology examination reveals a transient inflammatory cell infiltration at ID and IM injection sites which peaked at 48 h and 24 h, respectively, after immunization, with all side effects disappearing within one week. These results suggest that needle-free injection technology-based ID inoculation is a promising strategy for rabies vaccination in regard to safety and efficacy. [ABSTRACT FROM AUTHOR]

• The geometric mean concentration of the rabies virus-neutralizing activity in the ormutivimab group was no-inferior to that in the human rabies immunoglobulin (HRIG) group. • Ormutivimab had a weaker influence on the response of rabies vaccines than that in HRIG. • Ormutivimab showed higher safety with lower incidence of adverse reactions and grade Ⅲ adverse reactions. • Ormutivimab is an appropriate alternative to RIG as the passive immunity of postexposure prophylaxis. To evaluate the immunogenicity and safety of an anti-rabies monoclonal antibody (mAb), ormutivimab, compared with human rabies immunoglobulin (HRIG). This phase III trial was designed as a randomized, double-blind, non-inferiority clinical trial in patients aged ≥18 years with suspected World Health Organization category Ⅲ rabies exposure. The participants were randomized 1:1 to ormutivimab and HRIG groups. After thorough wound washing and injection of ormutivimab/HRIG on day 0, the vaccination was administered on days 0, 3, 7, 14, and 28. The primary endpoint was the adjusted geometric mean concentration (GMC) of rabies virus-neutralizing activity (RVNA) on day 7. The endpoint of safety included the occurrence of adverse reactions and serious adverse events. A total of 720 participants were recruited. The adjusted-GMC of RVNA (0.41 IU/ml) on day 7 in ormutivimab group was not inferior to that in the HRIG group (0.41 IU/ml), with ratio of adjusted-GMC of 1.01 (95% confidence interval: 0.91, 1.14). The seroconversion rate of the ormutivimab group was higher than that of the HRIG group on days 7, 14, and 42. Most local injection sites and systemic adverse reactions reported from both groups were mild to moderate in severity. ormutivimab + vaccine can protect victims aged ≥18 years with category Ⅲ suspected rabies exposure as a component of postexposure prophylaxis. ormutivimab has a weaker influence on the immunity response of rabies vaccines. ChiCTR1900021478 (the Chinese Clinical Trial Registry of World Health Organization). [ABSTRACT FROM AUTHOR]

Rabies, a viral disease spread by infected animal bites that causes encephalitis in humans and other mammals, is a neglected infectious disease present on all continents except Antarctica. Spain has been free of terrestrial rabies since 1978. However, due to its geographical situation, it represents a bridge for imported cases from an endemic continent such as Africa to Europe. Rabies vaccination in dogs is an essential preventive tool against this zoonosis. The aim of this study was to determine the state of the immune response against rabies virus in dogs in Spain and to demonstrate whether several factors that have been previously related to the influence of the seroprevalence of this species are involved here. The seroconversion level of this zoonotic virus was assessed in a total of 1060 animals. Indirect ELISA was used to obtain data for statistical analysis to evaluate the studied variables. Working under the concept of One Health, this study provides relevant information to be taken into consideration not only to prevent re-emergence in countries free of this disease but also for prevention and control in endemic countries.

PICO Question In free-roaming dog populations, does an egg-based oral rabies vaccination (ORV) compared with meat and fish based ORVs result in improved bait efficacy? Clinical bottom line Category of research Treatment. Number and type of study designs reviewed Three non-blinded, control trials were critically reviewed. Strength of evidence Weak. Outcomes reported Variables assessed in this Knowledge Summary included the type of bait that stray dogs were most interested in, and whether or not the dog was successfully vaccinated by release of the vaccine sachet into the oral cavity. Conclusion There is weak evidence to show that stray dogs prefer egg-based baits in compared to other bait types, despite egg-based baits allowing for more successful perforation of the vaccine sachet, and hence a higher chance of a successful oral rabies vaccination. How to apply this evidence in practice The application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. Knowledge Summaries are a resource to help reinforce or inform decision making. They do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care.

Background: To achieve well-regulated distribution, storage, and utilization of the rabies vaccine, health facilities should adhere to standard operating procedures. In Namibia, information on inventory management, utilization, monitoring, and reporting of rabies vaccine adherence to standard operating procedures in public healthcare facilities is insufficient. The aim of this study was to assess adherence to rabies vaccine standard operating procedures and inventory management and to compare rabies vaccine expenditure to the number of patients who received rabies vaccination at the Ministry of Health and Social Services' public healthcare facilities from 2018 to 2020. Methods: A cross-sectional, web-based questionnaire consisting of closed-ended questions was sent to 147 pharmacy staff and warehouse managers working in the 14 regions of Namibia during the period of May 1, 2021, to June 2, 2021. The overall expenditure and the total number of patients vaccinated from 2018 to 2020 were obtained from national-level logistic and vaccination program coordinators. Data were coded and transcribed into Microsoft® Excel® 2013 and analyzed using SPSS® version 27. Results: One hundred and thirty-three completed questionnaires were received from sixty-nine public health centers and hospitals. The group of respondents consisted of pharmacist assistants (50%), pharmacy technicians (12%), pharmacists (36.8%), senior pharmacists (0.8%), and chief pharmacists (1.5%). Overall, adherence to standard operating procedures was poor (27.1%). Rabies vaccine distributed to public health facilities from 2018 to 2020 was worth N$75,381,419.91 (~ US$4,074,671.46) and was expected to vaccinate 87,269 patients; however, only 95 cases of both rabies and rabid dog-bite patients were reported. The major inventory management challenges for public healthcare facilities include an inadequate number of pharmacy staff, poor adherence to standardized pharmaceutical warehousing, lack of regular supervision, and inadequate staff training. Conclusion: Inventory management practices in public healthcare facilities were not in compliance with standard operating procedures. There is a significant discrepancy between rabies vaccine expenditure and the number of patients that were vaccinated. Therefore, there is a need for adequate staff training on inventory management and regular facility supervision to enforce optimal rabies vaccine inventory management practices. [ABSTRACT FROM AUTHOR]

Aim: This study was aimed to develop rabies vaccine incorporated microneedle (MN) patches and evaluate the immunogenicity of prepared formulations in combination with iontophoresis. Methods: Patches comprising of polyvinyl pyrrolidone, hyaluronic acid and polyethylene glycol 400 were engineered by vacuum micromolding technique. Physical evaluation of patches included determination of folding endurance, % swelling and morphological features. In vitro release study was performed in skin simulant agarose gel using model drug (methylene blue) loaded patches. In vitro insertion ability was assessed using stratum corneum simulant parafilm. In vivo insertion study was performed in rats. Immunogenicity was evaluated in dogs by determining immunoglobulin G (IgG) and rabies virus neutralizing antibodies (RVNA) titer. Results: Patches displayed uniformly distributed microprojections with pointed tips and smooth surface, ~ 70% swelling, remained intact for ~ 200 foldings and successfully penetrated the parafilm. The area covered by model drug across agarose gel was almost double following treatment with MN-iontophoresis combination (MNdi) compared to MN alone (MNdo). Histological examination of rat skin treated with vaccine laden MN (MNvo) and MN-iontophoresis combination (MNvi) confirmed the formation of grooves in epidermis without any damage to the deep vasculature. A ~ 73% and ~ 206% increase (compared to untreated counterpart) was observed in the IgG titer of MNvo and MNvi treated dogs, respectively. The RVNA titer was increased by ~ 1.2 and ~ 2.2 times (compared to threshold value) after MNvo and MNvi treatment, respectively. Conclusion: MN-iontophoresis combination provided relatively potent immunogenic response over the conventional intramuscular injection, hence, can be used for administering vaccines transcutaneously. [ABSTRACT FROM AUTHOR]

Mounting evidence suggests that gut microbial composition and its metabolites, including short-chain fatty acids (SCFAs), have beneficial effects in regulating host immunogenicity to vaccines. However, it remains unknown whether and how SCFAs improve the immunogenicity of the rabies vaccine. In this study, we investigated the effect of SCFAs on the immune response to rabies vaccine in vancomycin (Vanco)- treated mice and found that oral gavage with butyrate-producing bacteria (C. butyricum) and butyrate supplementation elevated RABV-specific IgM, IgG, and virus-neutralizing antibodies (VNAs) in Vanco-treated mice. Supplementation with butyrate expanded antigen- specific CD4+ T cells and IFN-g-secreting cells, augmented germinal center (GC) B cell recruitment, promoted plasma cells (PCs) and RABV-specific antibody-secreting cells (ASCs) generation in Vanco-treated mice. Mechanistically, butyrate enhanced mitochondrial function and activated the Akt-mTOR pathway in primary B cells isolated from Vanco-treated mice, ultimately promoting B lymphocyte-induced maturation protein-1 (Blimp-1) expression and CD138+ PCs generation. These results highlight the important role of butyrate in alleviating Vanco-caused humoral immunity attenuation in rabies-vaccinated mice and maintaining host immune homeostasis. [ABSTRACT FROM AUTHOR]

This study was carried out to evaluate the effects of vitamin A (Vit A) and probiotic co-supplementation with rabies vaccine on humoral immune response in New Zealand white (NZW) rabbits. For this experiment, 54 rabbits were randomized into six experimental and three control groups. Mixed cultures of commercial probiotics supplements and a dose of Vit A were administered to each animal. Results were compared with the control group fed with only basal diet. Animals in different treatment groups showed significantly higher sero-conversions against rabies vaccine. There was a significant increase (p < 0.001) in the titers of rabies antibodies in all treatment groups on 14th and 35th days than control C3 group. Both commercial probiotics irrespective of brand increase the humoral immune response of rabbits against rabies vaccine. The mean titer values of all groups G1–G6 and sub-controls (C1, C2) were generally above 3.6 EU/ml on day 14th and between 3.7 and 3.9 EU/ml, showing highest sero-conversion on 35th day than mean titer of C3 control = 3.091 and 3.505 EU/ml respectively on both days. The maximum titer values were obtained with the addition of organic carrots to the daily diet. These results suggest that simple dietary interventions using probiotics and Vit A in natural form may enhance the efficacy of rabies vaccine in the host. These cost-effective strategies can be applied for getting higher yields of polyclonal antibody production in animal models, thus providing promising means of improving the final product yield and can be adopted easily by the manufacturers. [ABSTRACT FROM AUTHOR]

Rabies vaccines are highly effective and immunogenic in most populations, including when used as rabies post-exposure prophylaxis (RPEP); however, there is mounting evidence that the immune response to rabies vaccines, though predicted to be adequate, may be lower in older adults. Despite this, there are no specific recommendations in Canadian guidance to monitor the serological response of older adults following RPEP. Furthermore, while Canadian guidance recommends the intramuscular route for RPEP vaccination, there is good evidence supporting the immunogenicity, effectiveness and safety of RPEP vaccination using the intradermal route. We present a case of an 81-year-old male with rabies exposure who failed to respond to two series of RPEP with intramuscular rabies vaccination but responded to a third series using intradermal vaccine administration and provide reasoning for subsequent management. This case is brought forward to prompt discussion and research as to the utility of completing serology in older adults receiving RPEP as well as vaccination strategies, including route of administration, in those who do not respond to an initial course of RPEP vaccination. [ABSTRACT FROM AUTHOR]

This study established a new protocol of the antibody binding test to evaluate the potency of the rabies vaccine containing the final bulk and the product. The principle of this experiment is to combine rabies vaccine with quantitative anti-rabies virus neutralizing antibody. After combination, the remaining rabies vaccine is combined with the quantitative fluorescent labeled rabies virus. After this, observe the remaining fluorescent labeled rabies virus, calculate the fluorescence area with fluorescence observation equipment, then calculate the potency of rabies vaccine by Reed and Muench method. The test results of many batches of rabies vaccine final bulk and finished products showed that the potency detected by this method was consistent with that of National Institute of Health method. [ABSTRACT FROM AUTHOR]

Summary: Background: A vero cell-based inactivated Rabies Vaccine (Rabivax-S) and Rabies Human Monoclonal Antibody (Rabishield) have been approved since 2016. A post-marketing surveillance was conducted in India from 2020 to 2021 to gather real world safety data on Rabivax-S and Rabishield. Methods: This was non-interventional active surveillance in patients with category III potential rabies exposure who were administered a post-exposure prophylaxis (PEP) regimen (Rabishield and Rabivax-S) by their healthcare providers (HCPs) as per the dosages and regimens mentioned in the package insert approved by the Indian regulators. The approved schedule for PEP was local infiltration of Rabishield on Day 0 and five doses of Rabivax-S on Day 0, 3, 7, 14, and 28 (Intramuscular route, IM) or four doses of Rabivax-S on Day 0, 3, 7, and 28 (Intradermal route, ID). The primary objective of this surveillance was to generate real-world evidence on the safety and tolerability of Rabishield and Rabivax-S. All patients enrolled in the surveillance were required to report any adverse events (AEs) occurring up to Day 31 after initiation of PEP (administration of Rabishield and the first dose of Rabivax-S) to their HCP. Findings: A total of 1000 patients with category III potential rabies exposure were enrolled across India. 991 patients received the PEP regimen with IM Rabivax-S while 9 received a PEP regimen with the ID regimen. While 32% of the patients were

The aim of this study is to demonstrate that the freeze-dried human rabies vaccine (Vero cell), administered in a four-dose schedule (2-1-1) to the 10–60 years old population, has immunogenicity that is not inferior to the approved five-dose schedule and similar vaccines with a four-dose schedule, and to evaluate its safety. A total of 1800 individuals were enrolled and divided into three groups: four-dose test group, four-dose control group, and five-dose control group. The rabies virus neutralizing antibodies were measured using the Rapid Fluorescent Focus Inhibition Test to assess immunogenicity, and the incidence of adverse events and serious adverse events were statistically analyzed. The seroconversion rates 14 days after the first dose and 14 days after the complete course of vaccination were 100% in all three groups. The antibody GMC of the four-dose test group was higher than that of the five-dose control group, but slightly lower than the four-dose control group. Seven days after the first dose, both four-dose regimen groups showed higher seroconversion rates and antibody GMCs compared to the five-dose regimen group, proving that the immunogenic effect of the four-dose regimen seven days post-first vaccination is superior to the five-dose regimen. The overall incidence of adverse events showed no significant difference between the four-dose test group and the five-dose control group, but was significantly lower in the four-dose test group compared to the four-dose control group. The vaccine in the four-dose test group is equivalent in immunogenic effect to the four-dose control group vaccine and superior to the five-dose control group vaccine; the safety of the vaccine in the four-dose test group is equivalent to the five-dose control group vaccine and superior to the four-dose control group vaccine. clinicaltrials.gov number: NCT05549908. [ABSTRACT FROM AUTHOR]

This phase III clinical trial aimed to assess the safety and demonstrate the immunogenicity of a candidate freeze-dried purified Vero cell-based rabies vaccine (PVRV-WIBP) developed for human use. A cohort of 40 participants in stage 1 and 1956 subjects in stage 2 with an age range of 10–50 years were recruited for the phase III clinical trial. For safety analysis in stage 1, 20 participants received either 4-dose or 5-dose regimen of PVRV-WIBP. In stage 2, 1956 subjects were randomly divided into the 5-dose PVRV-WIBP, 5-dose PVRV-LNCD, and 4-dose PVRV-WIBP groups. The serum neutralizing antibody titer against rabies was determined on day 7 or 14 and day 35 or 42. Adverse reactions were recorded for more than 6 months. Most adverse reactions, which were mild and moderate in severity, occurred and resolved within 1 week after each injection in the PVRV-WIBP (4 and 5 doses) and PVRV-LNCD (5 doses) groups. All three groups achieved complete seroconversion 14 days after the initial dose and 14 days after completing the full vaccination schedule, the susceptible subjects in the PVRV-WIBP group (4-dose or 5-dose regimen) displayed higher neutralizing antibody titers against the rabies virus compared to those in the PVRV-LNCD group (5-dose regimen). PVRV-WIBP induced non-inferior immune responses versus PVRV-LNCD as assessed by seroconversion rate. PVRV-WIBP was well tolerated and non-inferior to PVRV-LNCD in healthy individuals aged 10–50 years. The results indicated that PVRV-WIBP (both 4- and 5-dose schedules) could be an alternative to rabies post-exposure prophylaxis.

The rabies virus is widely distributed and vaccines are an important strategy to prevent its spread. The whole-genome sequences of rabies strains in relation to vaccine development provide essential information to maintain vaccine quality and develop new vaccines. However, the genetic characteristics of the purified chick embryo cell culture rabies vaccine, KM Biologics (PCECV-KMB), developed in Japan in the 1970s, have not been explored. In this study, we conducted a genome-wide analysis of the open reading frame regions of rabies strains discovered from the 1940s–1980s and used to develop chick embryo cell-adapted HEP-Flury small plaque-forming (CEF-S) strain, which is a vaccine strain of PCECV-KMB. The genetic characteristic of CEF-S, developed by acclimation of the HEP-Flury-NIID strain to one-day eggs and subsequently to chick embryo cells, were confirmed by comparing the genome identity and revealing the nine amino acid mutations between CEF-S and HEP-Flury-NIID. The efficacy of PCECV-KMB was evaluated using attack strains isolated in Thailand in the 1960s–1970s during vaccine development. Phylogenetic analyses of the attack strains classified them in the same Asian clade as the 2000s imported cases from the Philippines to Japan, suggesting that PCECV-KMB is adequate for preventing the spread of the current rabies virus. [ABSTRACT FROM AUTHOR]

Rabies, a viral illness classified as a neglected tropical disease by the World Health Organization (WHO), causes thousands of people to die annually, primarily in underprivileged communities of Africa and Asia. In the context of a single health framework, one of the primary objectives of this literature review is to examine the major factors and challenges that maintain the endemic status of dog-mediated human rabies in Pakistan. Rabies-endemic countries have an imperative need to work on preventive strategies to lessen the burden of this terrible disease as per guidelines of World Organization for Animal Health (WOAH) and WHO. Lack of public awareness, free-roaming dogs, and cold chain mismanagement of vaccinations are the 3 most significant factors contributing to the increasing number of dog bite injuries and suspected rabies cases in animals and humans. To control dog-mediated rabies, Pakistan must initiate and strongly support a national One Health project, a subsidized supply of human and animal rabies vaccine in public hospitals, and designated rabies prevention centers at an affordable cost. People should be educated regarding responsible pet ownership and follow-up of basic preventive measures. Empowerment of labs equipped with surveillance systems are also additionally required to strengthen rabies control and prevention activities at least in regional levels. This article gives valuable information for scholars and policymakers who wish to comprehend why this disease remains endemic due to multiplex interplay of zoonotic, medical, and anthropological risk factors and transmission chains in animal and human sectors through viral reservoirs. Achieving the 'Zero By 2030' goal in Pakistan requires joint immediate action from the government, society, and all health departments at regional, provincial, and national level. [ABSTRACT FROM AUTHOR]

The core element of the reindeer rabies eradication strategy is regular application of vaccines to obtain and uphold a vaccination coverage sufficient for the ceasing of rabies virus transmission. This article presents the results of reindeer humoral immunity intensity and duration study after the immunization with two form of inactivated rabies vaccines (adjuvanted liquid vaccine and non-adjuvanted lyophilized vaccine) based on the Shchelkovo-51 rabies virus strain. Efficiency of post-vaccine immunity was assessed by measuring the animal blood serum virus-neutralizing antibody level in a neutralization test. The study determined the efficient rabies vaccine injection dose as equal to 3 ml. A single dose of 3 ml of these vaccines induced stable production of specific neutralizing antibodies in reindeer as early as 7 day after administration, and by 30 days after immunization, it significantly exceeded the minimal threshold level accepted by OIE. Two doses of vaccines administration with an interval of 30 days are required to achieve a strong immunity with the rabies-specific virus-neutralizing antibody titer of more than 0.5 IU/ml for at least 2 years. Our data do not support the benefit of an adjuvanted vaccine for the prevention of rabies in reindeer. [ABSTRACT FROM AUTHOR]

Background: Rapid fluorescent focus inhibition test (RFFIT), a neutralization-based assay for detecting rabies antibodies, is the gold standard. The National Action Plan for Dog Mediated Rabies Elimination (NAPRE) is a national program that strategizes the establishment of enzyme-linked immunosorbent assays (ELISA) to detect rabies antibodies., Objective: We developed an in-house ELISA to screen for rabies antibodies using rabies vaccine antigen to study vaccine response among health care workers (HCWs) who received pre-exposure prophylaxis and a few animal bite victims who received post-exposure prophylaxis with rabies vaccine., Study Design: A prospective study was carried out from April to September 2023 at the Department of Clinical Virology of a tertiary care center in South India. A total of 161 serum specimens, which included 155 serum samples from study participants and 6 samples from a reference laboratory (as controls), were obtained during the study period. Rabies antibody was determined by the in-house standardized ELISA developed using the rabies vaccine and compared with the reference assay, RFFIT. The accuracy indices of the in-house ELISA were estimated by MedCalc software (version 22.023)., Results: A panel of 86 positive and 75 negative serum samples was used for evaluating the in-house standardized ELISA. The sensitivity, specificity, positive and negative predictive values of the in-house ELISA were 98.8 %, 100 %, 100 %, and 98.7 % respectively. The accuracy of the in-house ELISA is 99.4 %., Conclusion: ELISA can be a practically feasible and less expensive assay compared to RFFIT which is a cumbersome procedure with a long turn-around time of 3-4 days., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Rabies is a zoonotic viral encephalitis that is endemic in many countries and confers a high mortality. Licensed vaccines require several doses to ensure efficacy. To investigate a logistically favorable approach, we assessed the safety and immunogenicity of ChAd155-RG, a novel investigational rabies vaccine using a replication-defective chimpanzee adenovirus vector., Methods: We conducted a first-in-human, phase 1, randomized, double-blind, dose-escalation trial comparing ChAd155-RG with a licensed inactivated vaccine (RabAvert) in healthy adults. Participants received either RabAvert at standard dosing or ChAd155-RG at a low dose for one immunization or a high dose for one or two immunizations. To assess safety, we evaluated reactogenicity, unsolicited adverse events, and thrombotic events. To measure immunogenicity, we measured rabies viral neutralizing antibody (VNA) titers and anti-ChAd155 neutralizing antibodies., Results: Mild to moderate systemic reactogenicity and transient lymphopenia and neutropenia were more common among recipients of ChAd155-RG compared with those who received RabAvert. No thrombotic events or serious adverse events were reported. Only the groups receiving RabAvert or two doses of high-dose ChAd155-RG achieved 100 % seroconversion, and seroprotection was most durable in the RabAvert group. Most participants had preexisting anti-vector antibodies, which were boosted by ChAd155-RG. Baseline and post-vaccination anti-vector antibody titers were negatively associated with post-vaccination rabies VNA titers., Conclusions: In this phase 1 clinical trial, a novel rabies vaccine using a simian adenovirus vector was safe and tolerable, but generated lower, less durable rabies VNA titers than a standard inactivated rabies virus vaccine, which may be due to preexisting, anti-vector immunity., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Varun K. Phadke reports financial support was provided by National Institute of Allergy and Infectious Diseases. Mark J. Mulligan reports financial support was provided by National Institute of Allergy and Infectious Diseases. Nadine Rouphael reports financial support was provided by National Institute of Allergy and Infectious Diseases. Jamie Retallick reports financial support was provided by National Institute of Allergy and Infectious Diseases. Janine Seetahal reports financial support was provided by National Institute of Allergy and Infectious Diseases. Mark Koller reports financial support was provided by National Institute of Allergy and Infectious Diseases. Nadine Rouphael reports a relationship with The Krog Group that includes: consulting or advisory. Nadine Rouphael reports a relationship with Virology Education that includes: speaking and lecture fees. Nadine Rouphael reports a relationship with Sanofi SA that includes: consulting or advisory and travel reimbursement. Nadine Rouphael reports a relationship with Moderna Inc. that includes: consulting or advisory and travel reimbursement. Nadine Rouphael reports a relationship with Seqirus Srl that includes: consulting or advisory. Nadine Rouphael reports a relationship with Pfizer Inc. that includes: consulting or advisory. Nadine Rouphael reports a relationship with The Emmes Company LLC that includes: consulting or advisory. Nadine Rouphael reports a relationship with ICON Clinical Research LLC that includes: consulting or advisory. Nadine Rouphael reports a relationship with Biomedical Advanced Research and Development Authority that includes: consulting or advisory. Nadine Rouphael reports a relationship with Cyanvac LLC that includes: consulting or advisory. Mark J. Mulligan reports a relationship with HilleVax, Inc. that includes: consulting or advisory. Mark J. Mulligan reports a relationship with Sanofi SA that includes: consulting or advisory. Mark J. Mulligan reports a relationship with Pfizer Inc. that includes: consulting or advisory. Mark J. Mulligan reports a relationship with Meissa Inc. that includes: consulting or advisory. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. GlaxoSmithKline was provided the opportunity to review a preliminary version of this manuscript for factual accuracy, but the authors are solely responsible for final content and interpretation. The authors have no conflicts of interest to disclose., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objectives: The World Health Organization recommends a 2-dose rabies pre-exposure prophylaxis (PrEP) regimen. This study aimed to compare the immunogenicity of rabies PrEP regimens co-administered with inactivated quadrivalent influenza vaccine (IIV4). Methods: Children aged 3 to 9 years were randomly assigned (2:2:1) to receive 0.25 mL of chromatographically purified Vero cell rabies vaccine intramuscularly: Group A at day 0, 7 with IIV4; Group B at day 0, 28 with IIV4; Group C at day 0, 7. A booster-dose of CPRV was given on day 365. Primary outcome was the proportion of children with protective rabies virus neutralizing antibody (RVNA) ≥ 0.5 IU/mL, on day 42 and 7 days post-booster. Results: From November 2019 to January 2020; 100 children with a median age (IQR) of 5.4 years (4.8-7.3) were enrolled. All participants achieved protective RVNA titers on day 42 and 7-days post booster. Geometric mean titers (GMT) at day 42 were Group A, 8.98(95%CI 7.06-11.42); Group B, 23.89(95%CI 19.33-29.51); Group C, 9.94(95%CI 7.03-14.06). Likewise, RVNA GMT at 7 days post-booster were Group A, 42.53(95%CI 18.41-66.64); Group B, 23.19(95%CI 17.28-29.10); Group C, 57.75 (95%CI 35.86-79.67). Conclusions: The 2-dose PrEP regimen of rabies vaccine produces adequate immune response either 0,7 or 0, 28 regimens.

The core element of the reindeer rabies eradication strategy is regular application of vaccines to obtain and uphold a vaccination coverage sufficient for the ceasing of rabies virus transmission. This article presents the results of reindeer humoral immunity intensity and duration study after the immunization with two form of inactivated rabies vaccines (adjuvanted liquid vaccine and non-adjuvanted lyophilized vaccine) based on the Shchelkovo-51 rabies virus strain. Efficiency of post-vaccine immunity was assessed by measuring the animal blood serum virus-neutralizing antibody level in a neutralization test. The study determined the efficient rabies vaccine injection dose as equal to 3 ml. A single dose of 3 ml of these vaccines induced stable production of specific neutralizing antibodies in reindeer as early as 7 day after administration, and by 30 days after immunization, it significantly exceeded the minimal threshold level accepted by OIE. Two doses of vaccines administration with an interval of 30 days are required to achieve a strong immunity with the rabies-specific virus-neutralizing antibody titer of more than 0.5 IU/ml for at least 2 years. Our data do not support the benefit of an adjuvanted vaccine for the prevention of rabies in reindeer.

Ormutivimab is the first recombinant human anti-rabies monoclonal antibody (rhRIG) approved for clinical application in China. In this study, a population pharmacodynamic (PPD) model was established to compare the neutralizing antibody activities of Ormutivimab and human rabies immunoglobulin (HRIG), alone or combined with human rabies vaccine (Vero), in a phase II clinical trial, and to recommend a target dose for the phase III trial. The model was verified to fit the PPD data well. The stability of the model was verified by the bootstrap method. The level of neutralizing antibodies in vivo increased rapidly after administration of Ormutivimab or HRIG. Neutralizing antibodies with a strong activity were produced at 7 days (Ormutivimab + vaccine) or 10 days (HRIG + vaccine) after induction by the vaccine in vivo. Compared to that induced by HRIG + vaccine, the level of the neutralizing antibodies induced by Ormutivimab + vaccine peaked higher and faster. The levels of neutralizing antibodies induced by Ormutivimab + vaccine and HRIG + vaccine were similar within 21 days after administration. According to these results and the safety data, 20 IU·kg−1 was recommended as the target dose in the confirmatory study of Ormutivimab. Registration: ClinicalTrials.gov #NCT02559921. [ABSTRACT FROM AUTHOR]

It is important to analyze the types of vaccines in travel clinics to determine the focus points in future practice.

Objective To evaluate the rate of adverse reaction toward rabies vaccine in China from 2008 to 2019, explore its characteristics and to provide a scientific and objective basis for future policy decisions. Methods Literature on the rate of adverse reaction to rabies vaccine in China from 2008 to 2019 was retrieved and collected in CNKI, Wanfang, VIP databases, PubMed and Embase. A meta analysis was carried out then. Results Totally, 35 articles were included. The combined rate of adverse reaction to rabies vaccine was 5.6% (95% CI = 5.1% – 6.0%). Adverse reactions to rabies vaccine were 11.3% and 4.5% before and after 2011, 5.3% and 7.1% in the eastern and midwestern regions, 13.2%, 25.5% and 3.7% in the tertiary hospitals, secondary hospitals and primary medical institutions, respectively. And 13.3% were in the areas where the Changchun immortal vaccine was used. The combined rate of adverse reaction to rabies vaccine inoculated in Changsheng vaccine area was 5.1%. Conclusion After 2011, the rate of adverse reaction to rabies vaccine in China has decreased dramatically. The rate of adverse reaction to rabies vaccine in the midwestern regions is higher than the counterpart in the eastern regions. The primary medical institutions are lower than the counterpart in the tertiary and secondary hospitals.

Background: Administering subsequent doses of rabies vaccine is not a medical emergency and does not require access to emergency department (ED) services. This study reviewed ED visits for rabies postexposure prophylaxis (PEP) to identify avoidable ED visits for subsequent rabies vaccination.Methods: This retrospective study included patients who received human rabies immune globulin (HRIG) or rabies vaccine at 15 EDs of a multi-hospital health system from 2016 to 2018. All ED visits were classified as initial or non-initial healthcare visits after animal exposure. Emergency department visits for non-initial healthcare were classified as necessary (HRIG administration, worsening symptoms, other emergent conditions, or vaccination during a natural disaster) or avoidable (rabies vaccination only).Results: This study included 145 patients with 203 ED visits (113 initial and 90 non-initial healthcare visits). Avoidable ED visits were identified for 19% (28 of 145) of patients and 66% (59 of 90) of ED visits for non-initial healthcare. Contributing factors for avoidable ED visits were suboptimal ED discharge instructions to return to the ED for vaccination (n = 20 visits) and patients' inability to coordinate outpatient follow-up (n = 17 visits). Patients with previous avoidable ED visits had a 73% probability for unnecessarily returning to the ED for vaccination. The average number of avoidable ED visits observed per patient was 0.41 (95% CI = 0.25 to 0.56). Since the Centers for Disease Control and Prevention reports that 30,000 to 60,000 Americans initiates rabies PEP each year, we estimate that 7500 to 33,600 avoidable ED visits occur for rabies vaccination in the US each year.Conclusions: One of 5 patients who received rabies PEP in the ED had avoidable ED visits for subsequent rabies vaccination. This study highlights systemic lack of coordination following ED discharge and barriers to accessing rabies vaccine. [ABSTRACT FROM AUTHOR]

• Phase IV, single-site, participant-blinded, randomized, placebo-controlled trial. • No effect of rabies vaccination on the incidence of self-reported illness episodes. • Little evidence that sex modifies the effect of vaccine on evaluated outcomes. Vaccines may affect recipients' immune systems in ways that change morbidity or mortality rates to unrelated infections in vaccinated populations. It has been proposed that these non-specific effects differ by type of vaccine and by sex, with non-live vaccines enhancing susceptibility of females to unrelated infections, and live vaccines enhancing resistance in both sexes. Rabies vaccine–a non-live vaccine–has been associated with protection against unrelated central nervous system infections. Data from randomized controlled trials are needed to assess this effect against other illnesses. This phase IV, single-site, participant-blinded, randomized, placebo-controlled trial in a population of veterinary students on the rabies-free island of St. Kitts assessed the effect of a primary course of rabies vaccine on the incidence rate of weekly self-reported new episodes of common infectious disease (CID) syndromes, defined as a new episode of any one of the following syndromes in a particular week: upper respiratory illness (URI), influenza-like illness (ILI), diarrheal illness (DIA) or undifferentiated febrile illness (UFI). As a secondary objective, we tested for modification of the effect of rabies vaccine on study outcomes by sex. 546 participants were randomized (274 to rabies vaccine and 272 to placebo). No statistically significant differences between groups were observed for any study outcomes: CID incidence rate ratio (IRR) 0.95 (95% CI 0.77–1.18); URI IRR 1.15 (95% CI 0.86–1.54); ILI IRR 0.83 (95% CI 0.54–1.27); DIA IRR 0.93 (95% CI 0.70–1.24) and UFI IRR 1.09 (95% CI 0.48–2.44). In a secondary analysis, there was little evidence that sex modified the effect of vaccination on any of the evaluated outcomes, although the power to detect this was low. In conclusion, rabies vaccine did not provide protection against mild self-reported illness among a young and healthy group of adults attending veterinary school. Clinical trial registration. ClinicalTrials.gov: NCT03656198. [ABSTRACT FROM AUTHOR]

• Rabies vaccine have been suggested to have beneficial non-specific effects in humans and dogs. • In rabies virus-free pigs, early life rabies vaccine was not associated with overall reduced mortality. • There was indication of a sex-differential rabies vaccine effect in litters of non-vaccinated sows. • Prior sow vaccination significantly modified the rabies vaccine effect in females. Human non-live vaccines have been associated with detrimental non-specific effects (NSE), particularly in females. A large trial found 2-fold increased overall mortality in girls receiving a new malaria vaccine compared to the rabies vaccine used as a coontrol; a beneficial NSE of the rabies vaccine was proposed. Conversely, in dogs increased mortality was seen in females but not males following rabies vaccination of puppies born to immunized mothers. We investigated NSE of non-live rabies vaccine in piglets and the potential modifying effect of maternal priming with rabies vaccine. In a Danish herd of commercial rabies virus-free pigs, 575 pregnant sows (2–3 weeks before scheduled farrowing) and 5747 of their offspring (median 6-day-old) were allocated (1:1) to non-live rabies vaccine (Versiguard rabies vet) or no rabies vaccine. Outcomes were overall mortality and antibiotic treatment until departure from the nursery (approximately age 12 weeks/30 kgs). Until weaning, overall offspring mortality was 2.2% (127 piglets died, rabies vaccine: n = 69; control: n = 58), the proportion ratio (PR) being 1.19 (95% confidence interval: 0.84–1.68). Until end of follow-up, mortality was 4.1% (233, rabies vaccine: n = 115; control = 118, PR: 0.97 (0.76–1.25)). Prior sow rabies vaccination did not affect piglet mortality. For mortality as well as risk of antibiotic treatment before weaning, there was indication of a beneficial effect of rabies vaccine in female piglets, but a negative effect in (castrated) male piglets from rabies-naïve sows. Prior sow vaccination significantly modified the vaccine effect estimate in female piglets toward a detrimental effect of rabies vaccine on treatment risk. These effects had waned by 12 weeks of age. The study did not support the hypothesized beneficial NSE of rabies vaccine. Although under-powered for subgroup analyses, the study indicated effect modification by sex and maternal vaccination. Results could be different in a herd with higher mortality and infectious burden. [ABSTRACT FROM AUTHOR]

Aim: The aims of the study were to evaluate the non-inferiority of the safety and immunogenicity of a new trial purified vero cell-cultured rabies vaccine (trial vaccine) in healthy subjects comparing with the control purified vero cell-cultured rabies vaccine (control vaccine) following Essen regimen and to evaluate the non-inferiority of the safety and immunogenicity of the trial vaccine following two intramuscular regimens, between Zagreb and Essen regimen. Methods: Serum samples were collected before vaccination and on d 7, 14, 35/42 post vaccination. Adverse events (AEs) were recorded for 30 d following each vaccination. This study was registered in the Chinese Clinical Trial Registry (ChiCTR-PPR-15007057). Results: There was no significant difference in the incidence of AEs, local and systemic reactions, among Zagreb group, Essen group, and control group. But the incidence of solicited AEs was a significant difference among the three groups (p = 0.0498). The incidence of solicited AEs was higher in Essen group than that in control group and Zagreb group (p = 0.0278, p = 0.0248). In the subjects whose antibodies were seronegative before vaccination, the seroconversion rates of antibodies among three groups were all 100.0% on d 14 and d 35/42. The Essen group was not inferior to the control group, and the Zagreb group was not inferior to the Essen group on d 14. On d 14 and d 35/42, the geometric mean concentration of the three groups was much higher than the immune protection level of 0.5 IU/ml. Conclusions: The trial vaccine had good safety and immunogenicity, and the trial vaccine is not inferior to the control vaccine. Abbreviations: PVRV: purified vero cell-cultured rabies vaccine; AE: adverse event; CI: confidence interval; GMC: geometric mean concentration; IM: intramuscular; NIFDC: National Institutes for Food and Drug Control; PPS: per-protocol set; SS: safety set; REFIT: Rapid Fluorescent Focus Inhibition Test; RVNA: rabies virus neutralizing antibody; WHO: World Health Organization.

Introduction: Rabies is a neglected zoonotic tropical disease that usually affects the poorest communities. Rabies is 100% fatal and at the same time 100% preventable. A huge proportion of death due to rabies occurs in Asia and Africa, and India is reported to have the highest incidence of rabies. Aims: To assess the knowledge, attitude, and practice related to animal bites, rabies, and its prevention and utilization of health services for this purpose in the study population. Methods: A community-based cross-sectional study done in an urban area among the age group 20 and above of both gender to assess and statistically highlight the knowledge, attitude, and practice related to animal bites, rabies, and its prevention and utilization of health services for this purpose in the study population. The sample size was estimated to be 350 and a simple random sampling technique was used for the selection of samples. Results: About 76% had heard about rabies. Among them only 63.5% knew it is a fatal disease, only 37.6% knew animals other than dogs can also cause rabies, only 37.3% of the study participants knew about appropriate first aid. Only 37.5% of the animal bite victims washed their wound with soap and running water and 35% had a full course of vaccination. Education had been an important factor that created a significant difference in the knowledge level of the participants. Conclusions: Improved community awareness, forestalling animal rabies, and better access to affordable and potent human rabies vaccines are essential for the elimination of human rabies.

Organ transplant recipients are at a high risk of infection with high hospitalization rate, critical rate and fatality, due to low immune function caused by taking immunosuppressants for a period of long time after organ transplantation. Currently, vaccination is recognized as an effective approach to prevent infection. Organ transplant recipients may be vaccinated according to individual conditions. However, the sensitivity to vaccines may decline in organ transplant recipients. The types, methods and timing of vaccination have constantly been the hot spots of clinical trials. In this article, the general principles, specific vaccines and SARS-CoV-2 vaccines of vaccination in organ transplant recipients were briefly reviewed, aiming to provide reference for the vaccination of organ transplant recipients. Moreover, current status of SARS-CoV-2 vaccination for organ transplant recipients was illustrated under the global outbreak of novel coronavirus pneumonia pandemic. [ABSTRACT FROM AUTHOR]

Rabies, caused by rabies virus (RABV), remains a serious threat to public health in most countries worldwide. At present, the administration of rabies vaccines has been the most effective strategy to control rabies. Herein, we evaluate the effect of colloidal manganese salt (Mn jelly [MnJ]) as an adjuvant of rabies vaccine in mice, cats, and dogs. The results showed that MnJ promoted type I interferon (IFN-I) and cytokine production in vitro and the maturation of dendritic cells (DCs) in vitro and in vivo. Besides, MnJ serving as an adjuvant for rabies vaccines could significantly facilitate the generation of T follicular helper (Tfh) cells, germinal center (GC) B cells, plasma cells (PCs), and RABV-specific antibody-secreting cells (ASCs), consequently improve the immunogenicity of rabies vaccines, and provide better protection against virulent RABV challenge. Similarly, MnJ enhanced the humoral immune response in cats and dogs as well. Collectively, our results suggest that MnJ can facilitate the maturation of DCs during rabies vaccination, which can be a promising adjuvant candidate for rabies vaccines. IMPORTANCE Extending the humoral immune response by using adjuvants is an important strategy for vaccine development. In this study, a novel adjuvant, MnJ, supplemented in rabies vaccines was evaluated in mice, cats, and dogs. Our results in the mouse model revealed that MnJ increased the numbers of mature DCs, Tfh cells, GC B cells, PCs, and RABV-specific ASCs, resulting in enhanced immunogenicity and protection rate of rabies vaccines. We further found that MnJ had the same stimulative effect in cats and dogs. Our study provides the first evidence that MnJ serving as a novel adjuvant of rabies vaccines can boost the immune response in both a mouse and pet model. [ABSTRACT FROM AUTHOR]

Purpose To study the appropriateness of rabies post-exposure prophylaxis (rPEP) for children with animal bite who visited the emergency department (ED). Methods The study enrolled children younger than 18 years with animal bite who visited the National Medical Center ED between January 2014 and October 2017. The children’s electronic medical records were retrospectively reviewed. Data for analysis included age, sex, body parts bitten by animals, species of animals, regions where animal bites occurred, history of recent antibiotics therapy and tetanus vaccination, and justification by the 2017 Guidelines for Rabies Control in Korea and implementation of rPEP. In children who underwent unjustified rPEP or did not undergo justified one, we recorded their guardians’ opinion for or against rPEP. Results Of the 63 enrolled children, rPEP was justified for 38 children by the Korean guidelines. Of the 38 children, 35 actually underwent rPEP. Among the remaining 3 children, 2 did not undergo the prophylaxis as per the guardians’ requests. Among the 25 children whose rPEP was not justified, 8 underwent the prophylaxis. Of these 8 children, 7 did based on the guardians’ requests. Conclusion In this study, inappropriate rPEP was usually affected by the guardians’ requests, regardless of the criteria for such prophylaxis. Thus, their requests for or against rPEP should be discussed with emergency physicians who are aware of the relevant criteria to prevent occurrence of rabies or unnecessary use of medical resources.

Abstract Background Vaccines may cause non-specific effects (NSEs) on morbidity and mortality through immune-mediated mechanisms that are not explained by the prevention of the targeted disease. Much of the evidence for NSEs comes from observational studies with a high risk of bias, and there is a clear need for new data from randomized controlled trials. Recently, it was proposed that rabies vaccine has protective NSEs in people and in animals. The aim of the proposed study is to determine whether rabies vaccine reduces the incidence rate of episodes of common infectious disease syndromes in a population of veterinary students on the island of St. Kitts. Methods The trial design is a single-site, two-arm, parallel-group, participant-blinded, randomized, placebo-controlled, two-sided comparative study, with an internal pilot study for blinded sample size re-estimation. Allocation to study arm is by block randomization stratified by sex within cohort with a 1:1 allocation ratio. The primary study outcome is the number of new weekly episodes of common infectious diseases including respiratory, diarrheal and febrile illnesses. A vaccine immunogenicity ancillary study is planned. Discussion Demonstration of a non-specific protective effect of rabies vaccine against unrelated respiratory, gastrointestinal and febrile illnesses would provide supportive evidence for the design of similar studies in children in populations with a high burden of these illnesses. Trial registration ClinicalTrials.gov, ID: NCT03656198 . Registered on 24 August 2018.

Rabies is an acute viral disease caused by a virus of the Rhabdoviridae family of the Lyssavirus genus, which affects the central nervous system and is characterised by absolute mortality. Vaccination is the only way to prevent the disease in humans. One of the products used for vaccination is a cultural concentrated purified inactivated dry rabies vaccine produced by the Federal State Budgetary Institution of Science “Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of Russian Academy of Sciences” (hereinafter—Chumakov Center).The aim of the study was to examine the structure of the working virus seed of Vnukovo-32 strain used by the Chumakov Center for rabies vaccine production, to assess its genetic stability during production, to explore the possibility of using molecular genetic methods for identification of the production strain in the finished dosage form, and to study the nucleotide sequence of the CVS strain.Materials and methods: Vnukovo-32 rabies virus production strain, working virus seeds, finished batches of the rabies vaccine, CVS fixed rabies virus strain used in the assessment of specific immunity. The molecular genetic study was performed using RT-PCR followed by restriction and sequencing.Results: the paper presents the results of nucleotide sequence analysis of the G gene fragment obtained from the Vnukovo-32 production strain, batches of the working virus seed, and finished batches of the rabies vaccine produced in 2012, 2018, and 2019, and the CVS fixed rabies virus strain used in the assessment of the vaccine’s specific immunity. The study demonstrated that restriction analysis could be used for Vnukovo-32 strain identification at all production stages, including the finished dosage form.Conclusion: Vnukovo-32 and CVS strains used by the Chumakov Center are rabies viruses. Analysis of the nucleotide sequence of the G gene fragment showed that the Vnukovo-32 strain remains stable throughout different production stages. The obtained nucleotide sequence of gene G of the Vnukovo-32 strain was deposited in GenBank (accession number MN116503). The study demonstrated that restriction analysis could be used for Vnukovo-32 strain identification at all production stages, including the finished dosage form.

Introduction: Repeated epidemiological studies to monitor trends of knowledge and practices are needed to guide strategies to control rabies. We conducted a study to assess the current knowledge, attitudes, and practices in relation to animal bites in the rural area of north India. Methods: House to house survey to collect data on animal bites was conducted among 300 households (assuming awareness regarding animal bites to be 25%, precision 95%, and power of 80%) from the rural area of Punjab, north India. A pretested semi-structured questionnaire comprising of items that explored sociodemographic details (age, educational qualification, occupation, socioeconomic status (assessed through Udai Pareek scale), and awareness regarding rabies, knowledge about first aid, attitude, and practices regarding anti-rabies vaccination (ARV) was used. Detailed questions were asked to those who owned pets. Results: A total of 300 households were included in the analysis. Among all respondents, 30.4% (117) had an episode of animal bite in their family giving a bite incidence rate of 78/1000 population. Bites were more frequent in males (65.8%, n = 77). The commonest site of the bite was lower limb (65%) followed by upper limb (21.4%), and head and neck (5.1%). The participants said that bites by pet animals (47%) are more common than those by stray animals (35.9%), followed by wild animals (12.8%). Almost 91% of respondents told that they would prefer govt. hospital for the treatment. Class I bite was most common (88.9%) followed by class II (8.5%) and class III (1.7%). A lot of respondents (41.4%) did not know about the symptoms of rabies in humans. Only 17.5% knew the appropriate wound care. Inappropriate practices like applying chilly (48.8%), lime (13.1%), tying the limb above the wound (5.1%), and others were common. Only 15.5% washed their wound with soap and water. Most of those who were bitten received post-exposure prophylaxis (PEP) (80%). Most of the respondents (98.3%) had heard about ARV but didn't know about the site of injection. Almost everyone (99.35) said that no awareness camps/programs had been conducted in their villages/school/health center to date. Conclusion: There is a high incidence of animal bites in rural areas. Awareness regarding the need for rabies vaccine of animals and PEP after an animal bite is quite high and is practiced. However, there is a lack of awareness regarding the course of action to be followed when an animal does develop rabies. Traditional and inappropriate practices of wound management persist and need to be countered. Improving the availability of ARV and rabies immunoglobulin through the public health system may further augment the uptake of PEP and completion of treatment while at the same time reducing out of pocket expenditure and the overall economic cost of rabies. Solid waste management in rural areas along with oral ARV is likely to reduce the incidence of rabies in rural areas.