Human Rabies Vaccine Research Articles

Inhibitory effect of concomitantly administered rabies immunoglobulins on the immunogenicity of commercial and candidate human rabies vaccines in hamsters

The World Health Organization protocol for rabies post-exposure prophylaxis (PEP) recommends extensive wound washing, immediate vaccination, and administration of rabies immunoglobulin (RIG) in severe category III exposures. Some studies have shown that RIG can interfere with rabies vaccine immunogenicity to some extent. We investigated the interference of RIG on a next generation highly purified Vero cell rabies vaccine candidate (PVRV-NG) versus standard-of-care vaccines in a previously described hamster model. The interference of either human (h) or equine (e) RIG on the immune response elicited by PVRV-NG, Verorab® (purified Vero cell rabies vaccine, PVRV), and Imovax® Rabies (human diploid cell rabies vaccine; HDCV) was evaluated using the 4-dose Essen PEP regimen. The anti-rabies seroneutralizing titers and specific serum IgM titers were measured by fluorescent antibody virus neutralization test and enzyme-linked immunosorbent assay, respectively, for the vaccines administered with or without RIG. The RIG interference on PVRV-NG, observed transiently at Day 7, was similar to that on PVRV and tended to be lower than that on HDCV using both read-outs. In summary, the results generated in the hamster model showed that RIG induced similar or less interference on PVRV-NG than the standard-of-care vaccines.

An ELISA-based antigenicity test of rabies recombinant glycoprotein cannot predict its protective potency in vivo

The potency of human and veterinary rabies vaccines is measured based on the National Institute of Health (NIH) potency test that is laborious, time-consuming, variable, and requires sacrifice of large numbers of mice. ELISA-based methods quantifying rabies glycoprotein (rGP) are being developed as potential alternatives to the NIH potency test for release of rabies vaccines. The aim of the current study was focused on the evaluation of in vitro- and in vivo-based assays in order to assess their concurrence for adequate and reliable assessment of immunogenicity and protective potency of a plant-derived recombinant rGP. The recombinant rGP of strain ERA.KK was engineered, expressed and purified from Nicotiana benthamiana plants. The recombinant rGP excluded the transmembrane and intracytoplasmic domains. It was purified by chromatography (≥90%) from the plant biomass, characterized, and mainly presented as high molecular weight forms, most likely soluble aggregates, of the rGP ectodomain. It was well-recognized and quantified by an ELISA, which utilizes two mouse monoclonal antibodies, D1-25 and 1112-1, and which should only recognize the native trimeric form of the rGP. However, in mice, the recombinant rGP did not induce the production of anti-rabies virus neutralizing antibodies and did not confer protection after intracerebral viral challenge. Similar immunogenicity was observed in guinea pigs and rabbits. Our results demonstrate that use of the ELISA method described here is not predictive of performance in vivo. These data highlight the critical need to develop in vitro potency assays that reliably define the antigen content that can induce a protective response.

Avoidable emergency department visits for rabies vaccination

BackgroundAdministering 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. MethodsThis 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). ResultsThis 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. ConclusionsOne 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.

Epitope Mapping of A Viral Propagation-Inhibiting Single-Chain Variable Fragment Against Rabies Lyssavirus Phosphoprotein.

Rabies is a highly neurotropic disease caused by rabies lyssavirus (RABV). Human rabies vaccines exist for pre- and postexposure prophylaxis; however, after clinical symptoms appear, the disease has an ∼100% mortality rate with no effective treatments available. In our previous study, mouse neuroblastoma cells transfected with a plasmid coding one clone of a single-chain variable fragment (scFv), scFv-P19, against RABV phosphoprotein (RABV-P) derived from an scFv phage-display library, before infection, exhibited reduced viral propagation after infection with the RABV-fixed strain, CVS11. In this study, we conducted epitope mapping of scFv-P19 through indirect fluorescent assay and Western blotting analysis against full-length and N- or C-terminal truncated RABV-P. Our results suggest that scFv-P19 targets a portion containing amino acids 47-52 at the N-terminus, which partially overlaps with the N-terminal nuclear export sequences. This provides insights into the underlying mechanism associated with inhibition of RABV by scFv-P19, while allowing for the design of additional scFv-based therapeutic studies for RABV by integrating appropriate delivery and application systems. Furthermore, the results of this study suggest that scFv-P19 may serve as an effective tool for investigating nuclear trafficking of RABV-P to explore the roles of RABV-P isoforms in rabies pathogenesis.

Immunogenicity and safety of human diploid cell vaccine (HDCV) vs. purified Vero cell vaccine (PVRV) vs. purified chick embryo cell vaccine (PCECV) used in post-exposure prophylaxis: a systematic review and meta-analysis

ABSTRACT This study comprehensively evaluated and compared three human rabies vaccines. Seven electronic databases were systematically searched. The Cochrane Handbook v5.1.0 was used to assess the risk of bias. A random-effects model was used to combine individual rates, and network meta-analysis was used for pairwise comparisons. Twenty-seven articles were included, with a total of 18,630 participants. The pooled incidence of the total adverse reaction to HDCV was significantly lower than that of PCECV. HDCV administration resulted in a lower incidence of local pain, fever, and weakness than purified Vero cell vaccine. HDCV caused a lower incidence of local pain and fever than PCECV. No significant difference was observed in terms of the seroconversion rate on day 7 or the rabies virus-neutralizing antibody titer on day 14. HDCV demonstrated superiority in terms of safety compared with the other two rabies vaccines, while the same was not observed in terms of immunogenicity.

A chemiluminescence immunoassay for precise automatic quality control of glycoprotein in human rabies vaccine

Currently, quality control of glycoprotein in the human rabies vaccine is based on enzyme-linked immunosorbent assay (ELISA). However, ELISA does not match the needs of a modernised quality control system. For a long time, human rabies virus vaccine manufacturers have been devoted to seeking a detection platform that is sensitive, accurate, automatic, and feasible for practical applications. Therefore, our team invested major efforts into establishing a fully automated micromagnetic particle (MMP)-based chemiluminescence immunoassay (CLIA) platform. For vaccine quality control, MMP-coupled rabies virus glycoprotein monoclonal antibodies (S037) were used to capture the rabies virus. Another rabies virus glycoprotein antibody (S053) labelled with acridinium ester was added as a signal tracer. After pretreating the vaccine sample, the entire analysis was performed using a fully automated machine, which had a limited detection time (only 30 min) and eliminated manual error. Multiple experiments have identified the optimal conditions allowing valid and reliable assessment of vaccine potency. The CLIA platform has exhibited merits in terms of speed, robustness, high sensitivity (with a minimum detection value of 0.45 mIU/mL), considerable accuracy, and a wide linear range of detection (9.4–1200 mIU/mL). Furthermore, the results showed that the CLIA platform is consistent with the National Institutes of Health test and time-resolved fluorescent immunoassay (TRFIA) in quantitative analysis, and had a better analytic performance than TRFIA. Therefore, the CLIA platform presented here may be important for application in modern vaccine quality control.

Vaccine bidding, procurement and distribution management practices in mainland China: A nationwide study

ObjectiveTo conduct a nationwide evaluation of vaccine bidding, procurement and distribution management for understanding and improving the current situation well in mainland China. MethodsAn institution survey was carried out to collect information on tendering, procurement, distribution and related issues to vaccines by structured questionnaires administered to 31 provinces in mainland China from April to July 2019. ResultsIn 13 (41.9%) of 31 provinces, centralized bidding of National Immunization Program (NIP) vaccines was accomplished, and others conducted independent tendering and purchasing in 2018. For non-NIP vaccines, all provinces implemented unified bidding at the provincial level and over half (18, 58.1%) of them chose provincial public resource trading platforms, but their modes varied over provinces. Then procurement was undertaken by the district-level centers for disease control and prevention (CDC) while they were unable to choose the best option of too many vaccines targeted by the province-level CDC for local populations. The distribution modes of NIP and non-National Immunization Program (non-NIP) vaccines were similar overall in a province but very different over provinces. Main mode was that CDCs at different levels delivered about two thirds (64.5%) of NIP vaccines distribution and more than one third (35.5%) of non-NIP vaccines. Another distribution mode was occupied as fully buying the service from third parties in 3 municipalities. Some provinces mixed both modes, too. The total distribution volume of vaccines was 430.7 million doses in 2018. The top five non-NIP vaccines delivered in 2018 were human rabies vaccine, varicella vaccine, EV71 hand foot mouth disease vaccine, hepatitis B vaccine and influenza vaccine. ConclusionThe vaccine biding, procurement and distribution management varied over provinces in mainland China in 2018, especially for non-NIP vaccines. Specific policies and measures should be developed for different regions to improve the immunization management better.

Assessing Rabies Vaccine Protection against a Novel Lyssavirus, Kotalahti Bat Lyssavirus.

Rabies is a fatal encephalitis caused by an important group of viruses within the Lyssavirus genus. The prototype virus, rabies virus, is still the most commonly reported lyssavirus and causes approximately 59,000 human fatalities annually. The human and animal burden of the other lyssavirus species is undefined. The original reports for the novel lyssavirus, Kotalahti bat lyssavirus (KBLV), were based on the detection of viral RNA alone. In this report we describe the successful generation of a live recombinant virus, cSN-KBLV; where the full-length genome clone of RABV vaccine strain, SAD-B19, was constructed with the glycoprotein of KBLV. Subsequent in vitro characterisation of cSN-KBLV is described here. In addition, the ability of a human rabies vaccine to confer protective immunity in vivo following challenge with this recombinant virus was assessed. Naïve or vaccinated mice were infected intracerebrally with a dose of 100 focus-forming units/30 µL of cSN-KBLV; all naïve mice and 8% (n = 1/12) of the vaccinated mice succumbed to the challenge, whilst 92% (n = 11/12) of the vaccinated mice survived to the end of the experiment. This report provides strong evidence for cross-neutralisation and cross-protection of cSN-KBLV using purified Vero cell rabies vaccine.

Long-term immunity and the effect of one or two booster doses with a lyophilized human rabies vaccine (human diploid cells) at 10 years post primary vaccination in China

ABSTRACT Background: To evaluate the persistence of antibody for 10 years, and investigate the effect of one or two booster doses with Kanghua human diploid cells rabies vaccine (HDCV) in China. Methods: Participants were re-recruited at year 10 post the primary phase 3 clinical study. Some of them in Kanghua HDCV group who had been boosted one dose at year 8, received one more dose at this boosted study. Participants who never boosted were randomly assigned to boost 1 or 2 doses of Kanghua HDCV. Blood samples were collected at day 0, 1, 3, 7, and 14. Safety was evaluated from day 0–14. Results: At year 10 after primary vaccination, the seroconversion rates of neutralizing antibody were 98.28–100% in Kanghua and Pasteur groups. After booster, the seroconversion rate in each group reached to 100% from day 7 to day 14. GMCs were similar in the groups with the same booster doses, and two doses of booster induced higher levels of antibody. The reported rates of solicited local and systemic adverse reaction were low, and no serious adverse events were found through the boosted study. Conclusion: 5 doses of Kanghua HDCV maintained long-term immunity at least 10 years. One or two doses of booster, rapidly triggered 100% protection against rabies virus. Trial registration: ClinicalTrials.gov: NCT03774628

How geographic access to care shapes disease burden: The current impact of post-exposure prophylaxis and potential for expanded access to prevent human rabies deaths in Madagascar.

Post-exposure prophylaxis (PEP) is highly effective at preventing human rabies deaths, however access to PEP is limited in many rabies endemic countries. The 2018 decision by Gavi to add human rabies vaccine to its investment portfolio should expand PEP availability and reduce rabies deaths. We explore how geographic access to PEP impacts the rabies burden in Madagascar and the potential benefits of improved provisioning. We use spatially resolved data on numbers of bite patients seeking PEP across Madagascar and estimates of travel times to the closest clinic providing PEP (N = 31) in a Bayesian regression framework to estimate how geographic access predicts reported bite incidence. We find that travel times strongly predict reported bite incidence across the country. Using resulting estimates in an adapted decision tree, we extrapolate rabies deaths and reporting and find that geographic access to PEP shapes burden sub-nationally. We estimate 960 human rabies deaths annually (95% Prediction Intervals (PI): 790-1120), with PEP averting an additional 800 deaths (95% PI: 640-970) each year. Under these assumptions, we find that expanding PEP to one clinic per district (83 additional clinics) could reduce deaths by 19%, but even with all major primary clinics provisioning PEP (1733 additional clinics), we still expect substantial rabies mortality. Our quantitative estimates are most sensitive to assumptions of underlying rabies exposure incidence, but qualitative patterns of the impacts of travel times and expanded PEP access are robust. PEP is effective at preventing rabies deaths, and in the absence of strong surveillance, targeting underserved populations may be the most equitable way to provision PEP. Given the potential for countries to use Gavi funding to expand access to PEP in the coming years, this framework could be used as a first step to guide expansion and improve targeting of interventions in similar endemic settings where PEP access is geographically restricted and baseline data on rabies risk is lacking. While better PEP access should save many lives, improved outreach, surveillance, and dog vaccination will be necessary, and if rolled out with Gavi investment, could catalyze progress towards achieving zero rabies deaths.

Knowledge, attitude, and practice study on animal bite, rabies, and its prevention in an urban community.

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.

Development of competitive inhibition ELISA as an effective potency test to analyze human rabies vaccines and assessment of the antigenic epitope of rabies glycoprotein

The potency of all modern tissue culture human rabies vaccines is measured based on the National Institute of Health (NIH) potency test that is laborious, time-consuming, involves large test variations and requires sacrifice of large number of animals. To circumvent these limitations, several researchers and WHO expert working groups have discussed development of alternative in vitro methods to replace the NIH potency test. Although several immunochemical methods have been proposed to quantify rabies glycoprotein (G-protein) using multiple murine monoclonal antibodies, we report an In vitro competitive inhibition ELISA (CIA) method based on the use of a neutralizing rabies glycoprotein site III directed novel therapeutic human rabies monoclonal antibody (RAB1) that shows equivalence to the mice NIH potency test in recognition of neutralization site of the glycoprotein. In vitro potency testing of WHO 7th International Standard for rabies vaccine (IS) by CIA using RAB1 and In-house reference standard (IHRS) as a standard to assess its suitability for the assessment of validation parameters showed accurate and precise values with <15% coefficient variance. The method was validated using 5PL standard curve with linearity r2 > 0.98 and LLOQ of 0.125 IU/mL indicating sensitivity of the method. The method was found to be precise, robust and accurate to quantitate intact rabies glycoprotein in final vaccine and showed a strong correlation (Pearson's r = 0.81) with the NIH potency values of licensed Vero cell rabies vaccine. The CIA test using RAB1 was able to accurately quantitate degradation of rabies vaccine and assess loss in antigenicity of lyophilized and reconstituted liquid rabies vaccine under thermal stress conditions. The method was able to differentiate between potent and reduced potency vaccine samples. The new in vitro competitive inhibition ELISA method using RAB1 thus can be a valid alternative to the NIH test.

Role of Oral Rabies Vaccines in the Elimination of Dog-Mediated Human Rabies Deaths.

Domestic dogs are responsible for nearly all the »59,000 global human rabies deaths that occur annually. Numerous control measures have been successful at eliminating dog-mediated human rabies deaths in upper-income countries, including dog population management, parenteral dog vaccination programs, access to human rabies vaccines, and education programs for bite prevention and wound treatment. Implementing these techniques in resource-poor settings can be challenging; perhaps the greatest challenge is maintaining adequate herd immunity in free-roaming dog populations. Oral rabies vaccines have been a cornerstone in rabies virus elimination from wildlife populations; however, oral vaccines have never been effectively used to control dog-mediated rabies. Here, we convey the perspectives of the World Organisation for Animal Health Rabies Reference Laboratory Directors, the World Organisation for Animal Health expert committee on dog rabies control, and World Health Organization regarding the role of oral vaccines for dogs. We also issue recommendations for overcoming hesitations to expedited field use of appropriate oral vaccines.

Update on lyssaviruses and rabies: will past progress play as prologue in the near term towards future elimination?

Rabies is an ancient, much-feared, and neglected infectious disease. Caused by pathogens in the family Rhabdoviridae, genus Lyssavirus, and distributed globally, this viral zoonosis results in tens of thousands of human fatalities and millions of exposures annually. All mammals are believed susceptible, but only certain taxa act as reservoirs. Dependence upon direct routing to, replication within, and passage from the central nervous system serves as a basic viral strategy for perpetuation. By a combination of stealth and subversion, lyssaviruses are quintessential neurotropic agents and cause an acute, progressive encephalitis. No treatment exists, so prevention is the key. Although not a disease considered for eradication, something of a modern rebirth has been occurring within the field as of late with regard to detection, prevention, and management as well as applied research. For example, within the past decade, new lyssaviruses have been characterized; sensitive and specific diagnostics have been optimized; pure, potent, safe, and efficacious human biologics have improved human prophylaxis; regional efforts have controlled canine rabies by mass immunization; wildlife rabies has been controlled by oral rabies vaccination over large geographic areas in Europe and North America; and debate has resumed over the controversial topic of therapy. Based upon such progress to date, there are certain expectations for the next 10 years. These include pathogen discovery, to uncover additional lyssaviruses in the Old World; laboratory-based surveillance enhancement by simplified, rapid testing; anti-viral drug appearance, based upon an improved appreciation of viral pathobiology and host response; and improvements to canine rabies elimination regionally throughout Africa, Asia, and the Americas by application of the best technical, organizational, economic, and socio-political practices. Significantly, anticipated Gavi support will enable improved access of human rabies vaccines in lesser developed countries at a national level, with integrated bite management, dose-sparing regimens, and a 1 week vaccination schedule.

Analysis Strategies for Rabies Prevention and Control in China

Objective To analyze the current epidemiological characteristics of rabies in China, grasp the law of epidemic changes, and provide scientific basis for rabies prevention and control strategies in China. Methods The data of human rabies prevention and control in China were systematically collected, combined with the genetic sequences of rabies virus street virus epidemic strains in various provinces of China, and statistical and molecular biological methods were used for statistics and analysis. Results The number of rabies cases and deaths in China has decreased year by year. At present, the main method of human rabies transmission in China is dog injury. Post-exposure treatment showed an increase in the rate of self-treatment, a decline in the overall immunity rate of the vaccine, and an increase in the rate of passive immunity. Human rabies vaccines are currently available to meet vaccination needs. In addition, the immune rates of dogs and cats did not change significantly. The rabies street virus strains in China are mainly divided into 6 species including China Ⅰ-China Ⅵ. Conclusion In terms of infrastructure, it is still necessary to increase the number of primary clinics, improve the professional capabilities of medical staff, and strengthen publicity and education on rabies prevention and treatment. In the areas with high incidence of cases, vaccines similar to street strain should be selected for immunization of human and animal.

Zero human deaths from dog-mediated rabies by 2030: perspectives from quantitative and mathematical modelling.

Dog-mediated rabies continues to kill tens of thousands of people every year in low- and middle-income countries despite being an entirely vaccine-preventable disease. WHO and partners have launched a global campaign to reach zero human deaths from dog-mediated rabies by 2030. The primary tools for reaching this target are mass dog vaccination to interrupt transmission in domestic dog populations that maintain infection, appropriate post-exposure prophylaxis (PEP) for rabies-exposed persons to prevent the fatal onset of disease, together with education to support their effective uptake. Models have been developed to assess the feasibility, impact and cost-effectiveness of these measures. From these models, we argue that the 2030 target of zero human rabies deaths is achievable, but will require concerted effort, engagement and investment. A proposed Gavi investment in human rabies vaccines has potential to drive progress towards the 2030 target; however, concomitant investment is needed to scale up mass dog vaccination or this target will be missed. Predicted economic benefits of mass dog vaccination vary according to national PEP provisioning and healthcare access. Integrated Bite Case Management can enhance surveillance and rationalize PEP use, but needs adapting to and integrating within local health systems and international reporting systems to improve PEP accountability, monitor impacts and support verification of disease freedom. Modelling approaches need refining to project realistic and geographically specific timelines for achieving targets. Model iterations informed by data on the implementation of interventions can be used to evaluate progress and guide future strategies. Critically such models are needed to advocate for investment, since the greatest risk to the 'Zero by 30' strategy is the limited long-term cross-sectoral or targeted financing to support countries to deliver and sustain mass dog vaccination.

A novel ELISA for quantification of glycoprotein in human rabies vaccines using a clinically proven virus neutralizing human monoclonal antibody

ABSTRACT Global efforts on the replacement of the in vivo rabies vaccine potency test (NIH method) with in vitro methods for quantification of immunodominant glycoprotein (GP) in rabies vaccine have made significant progress. We report here, a sandwich ELISA method based on the use of a neutralizing rabies GP site III directed human monoclonal antibody (RAB-1) and a polyclonal GP specific antibody recognizing the intact form of viral GP. The method was shown to be robust, specific, linear, precise and accurate in the quantification of intact GP in vaccine samples. The assay was able to differentiate between potent and sub-potent vaccine samples. The assay was shown to be linear over the range of 0.07–2.25 IU/mL with LOD and LLOQ values of 0.035 and 0.070 IU/mL, respectively. The assay was able to quantify the GP content of rabies vaccines derived from rabies vaccine strains, e.g., Pittman-Moore, Pasteur and Flury LEP with acceptable precision (CV < 20%) and also showed good agreement with NIH potency estimates. The binding kinetics of RAB-1 with intact and modified vaccine samples were also characterized using biolayer interferometry (BLI). The developed method may be used as an alternative to the NIH method in quality control testing of human rabies vaccines.

Retrospective study of immunization errors reported in an online Information System.

Objective:to analyze the immunization errors reported in an online Information System.Method:retrospective study conducted with data from the Adverse Event Following Immunization Surveillance Information System. Immunization errors were analyzed with respect to demographic characteristics and the vaccination process. Frequencies and error incidence rates have been calculated. Binomial and chi-square tests were used to verify differences in the proportions of the variables.Results:501 errors were analyzed, the majority involving routine doses (92.6%), without Adverse Event Following Immunization (90.6%) and in children under five years old (55.7%). The most frequent types of errors were inadequacy in the indication of the immunobiological (26.9%), inadequate interval between doses (18.2%) and error in the administration technique (14.2%). The overall error incidence rate was 4.05/100,000 doses applied; the highest incidences of routine vaccines were for human rabies vaccine, human papillomavirus and triple viral; the incidence rate of errors with Adverse Events Following Immunization was 0.45/100,000 doses applied.Conclusion:it was found that immunization errors are a reality to be faced by the health systems, but they are amenable to prevention through interventions such as the adoption of protocols, checklists and permanent education in health.

Zero human deaths from dog-mediated rabies by 2030: insights from modelling

Dog-mediated rabies continues to kill tens of thousands of people every year in low- and middle-income countries despite being an entirely vaccine-preventable disease. WHO and partners have launched a global campaign to reach zero human deaths from dog-mediated rabies by 2030. The primary tools for reaching this target are mass dog vaccination to control and interrupt transmission in domestic dog populations that maintain infection, and appropriate post-exposure prophylaxis (PEP) for rabies-exposed persons to prevent the fatal onset of disease. Models have been developed to assess the feasibility, impact and cost-effectiveness of these measures. From these models, we argue that the 2030 target of zero human rabies deaths is achievable, but will require concerted effort, engagement and investment. A proposed Gavi investment in human rabies vaccines has potential to drive progress towards the 2030 target; however, concomitant investment is needed to scale up mass dog vaccination or this target will be missed. Predicted economic benefits of mass dog vaccination vary according to national PEP provisioning and access to care. Integrated Bite Case Management can enhance surveillance and rationalize PEP use, but needs adapting to and integrating within local health systems and international reporting systems to improve PEP accountability, monitor impacts and support verification of disease freedom. Modelling is required for projecting more realistic and geographically specific timelines for achieving targets, in line with the implementation of interventions. The greatest risk to the ‘Zero by 30’ strategy is the limited long-term cross-sectoral or targeted financing to support countries to deliver and sustain mass dog vaccination.

Cross-Protection of Inactivated Rabies Vaccines for Veterinary Use against Bat Lyssaviruses Occurring in Europe.

Human rabies vaccines have been shown to induce partial protection against members of phylogroup I bat lyssaviruses. Here, we investigated the capacity of a widely used rabies inactivated vaccine (Rabisin, Boehringer-Ingelheim) for veterinary use to cross-protect mice experimentally infected with European bat lyssavirus 1 (EBLV-1b), European bat lyssavirus 2 (EBLV-2), and Bokeloh bat lyssavirus (BBLV) occurring in Europe. For each lyssavirus, we investigated the efficacy of two different doses of vaccine against two viral doses administrated by either central or peripheral routes. In parallel, seroconversion following pre-exposure vaccination was investigated. In this study, we demonstrated that the three investigated bat isolates were pathogenic, even at low dose, when inoculated by the central route but were not/less pathogenic when administrated peripherally. The Rabisin vaccine was capable of significantly cross-protecting mice inoculated intramuscularly with EBLV-1b and EBLV-2 and intracerebrally with BBLV. The level of rabies neutralizing antibodies induced by the Rabisin was quite high against the bat lyssaviruses, but with no significant differences between immunization with 1 and 5 IU/dose. The study emphasizes that the quality of rabies-inactivated vaccines for veterinary use is of utmost importance to optimize the cross-protection of pets against phylogroup I bat lyssaviruses occurring in Europe.