Background: Rabies is one of the fatal diseases which is primarily a vaccine-preventable zoonotic disease transmitted to man usually by bites or licks of rabid animals. Objectives: This study aimed ...to assess the compliance and health-seeking behavior of the beneficiaries attending anti-rabies vaccination out patient department (OPD) of a tertiary care hospital along with the out-of-pocket expenditure required for vaccination. Materials and Methods: A longitudinal study was conducted in the anti-rabies vaccination (ARV) OPD of a tertiary care hospital in India. A total of 149 animal bite victims were included in the study. The beneficiaries coming for first and second doses in 1 month for Anti-Rabies vaccine were enrolled in the study and followed telephonically for 1 month for compliance with the ARV vaccines. Results: The median age of the study participants was 32 years ranging from 4 to 75 years. 73.8% were males, while 26.2% were females. A total of 26.84% did not follow the initial wound management protocol and the mean delay in seeking medical care was 22 ± 4.6 h. A majority (86%) were dog bites and 32.6% were found to be noncompliant to the schedule of the vaccination. The average out-of pocket expenditure borne by beneficiaries for getting vaccination was Rs. 462 ($5.54). Conclusions: A large number of victims of animal bite were not compliant with the schedule, and many had not completed the schedule. The out of pocket expenditure of the victims was high.
Rabies, caused by the rabies virus (RABV), is the most fatal zoonotic disease. It is a neglected tropical disease which remains a major public health problem, causing approximately 59,000 deaths ...worldwide annually. Despite the existence of effective vaccines, the high incidence of human rabies is mainly linked to tedious vaccine immunisation procedures and the overall high cost of post-exposure prophylaxis. Therefore, it is necessary to develop an effective vaccine that has a simple procedure and is affordable to prevent rabies infection in humans. RABV belongs to the genus Lyssavirus and family Rhabdoviridae. Previous phylogenetic analyses have identified seven major clades of RABV in China (China I-VII), confirmed by analysing nucleotide sequences from both the G and N proteins. This study evaluated the immunogenicity and protective capacity of SYS6008, an mRNA rabies vaccine expressing rabies virus glycoprotein, in mice and cynomolgus macaques. We demonstrated that SYS6008 induced sufficient levels of rabies neutralising antibody (RVNA) in mice. In addition, SYS6008 elicited strong and durable RVNA responses in vaccinated cynomolgus macaques. In the pre-exposure prophylaxis murine model, one or two injections of SYS6008 at 1/10 or 1/30 of dosage provided protection against a challenge with a 30-fold LD50 of rabies virus (China I and II clades). We also demonstrated that in the post-exposure prophylaxis murine model, which was exposed to lethal rabies virus (China I-VII clades) before vaccination, one or two injections of SYS6008 at both 1/10 and 1/30 dosages provided better protection against rabies virus challenge than the immunization by five injections of commercial vaccines at the same dosage. In addition, we proved that SYS6008-induced RVNAs could neutralise RABV from the China I-VII clades. Finally, 1/10 of the dosage of SYS6008 was able to stimulate significant RABV-G specificity in the T cell response. Furthermore, we found that SYS6008 induced high cellular immunity, including RABV-G-specific T cell responses and memory B cells. Our results imply that the SYS6008 rabies vaccine, with a much simpler vaccination procedure, better immunogenicity, and enhanced protective capacity, could be a candidate vaccine for post-exposure prophylaxis of rabies infections.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract Regulatory potency test for rabies vaccines requires mice vaccination followed by challenge with a live virus via intracerebral route. An alternative in vitro test, consistent with the ...“3R's” (Reduce, Replace, Refine) was designed to quantify active glycoprotein G using seroneutralizing monoclonal antibodies. This versatile ELISA targets well conformed neutralizing epitopes. Therefore, it quantifies only the trimeric pre-fusion form of glycoprotein G known to elicits the production of viral neutralizing antibodies. The ELISA makes it possible to quantify the rabies antigen during all steps of the product cycle ( i.e. viral cultivation, downstream process, formulation and product stability in the presence of aluminum gel or other vaccine valence). Moreover, the batch-to-batch consistency of our active ingredients and formulated products could be demonstrated.
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•Seroconversion >95% persisted at 5 years for the 1-week 4-site ID regimen in Group 1.•Seroconversion persisted between 80 and 90% in Group 2.•Seroconversion rates in Group 3 decreased from 80% at ...Year 1 to 64% at Year 5.•A 4-site ID booster 5 years after primary vaccination induced 100% anamnestic responses.
In a randomized controlled study (NCT01622062) a 1-week, 4-site intradermal (ID, 4-4-4-0-0) post-exposure prophylaxis (PEP) rabies vaccination regimen with purified Vero cell rabies vaccine (PVRV, Verorab®, Sanofi Pasteur), either without (Group 1) or with (Group 2) purified equine rabies immunoglobulin (ERIG), patients in the Philippines achieved seroconversion rates at Day 14 that were non-inferior to that of the updated Thai Red Cross (TRC) 28-day, 2-site (2-2-2-0-2) ID regimen with ERIG (Group 3). Presented here are the annual immunogenicity data up to five years after the last primary dose, and the immunogenicity and safety data following simulated PEP with single-visit, 4-site ID regimen.
Rabies virus neutralizing antibodies (RVNA) were determined by rapid fluorescent focus inhibition test (RFFIT). Participants (n = 397) received simulated PEP vaccination ID at Year 5 and RVNAs were assessed at Day 11 post-vaccination.
Seroconversion rates (RVNA titres ≥ 0.5 IU/mL) during annual follow-up remained >95% in Group 1 and were relatively stable at 80–90% in Group 2, but decreased from 80% to 64% in Group 3. RVNA geometric mean titres (GMTs) in Group 1 were consistently higher than in the other two groups, and those in Group 3 were generally lower than in the other two groups. There was a clear anamnestic response to vaccination in all groups, with all participants achieving RVNA titres ≥ 0.5 IU/mL at Day 11 post-simulated PEP booster vaccination. There were no safety concerns raised during annual follow-up and with simulated post-exposure vaccination with PVRV.
The shortened, 1-week, 4-site ID regimen with PVRV achieved persistently higher RVNA titres than the updated 2-site TRC regimen, and more participants remained seroprotected up to five years after the last dose of primary immunization. Simulated post-exposure with 4-site ID rapidly induced an anamnestic response indicative of robust protection.
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Rabies virus, as a neurotropic agent, is transmitted to humans usually after animal biting. Rabies is endemic in most Middle Eastern countries. Pre-exposure Prophylaxis (PrEP) program is recommended ...for high-risk populations in endemic areas. The present study reported 7 deaths from rabies infection despite human Post-Exposure Prophylaxis (PEP) and the evolution of their possible etiologies from 2014 to 2018 in Iran. In this study, 29 rabid human deaths were evaluated despite PEP in 2014-2018. Seven people deceased despite receiving PEP. The most damaged organs were hands and face (71.43%). Injecting anti-Rabies Immunoglobulin (RIG) around the wound, improper cleansing, and delayed PEP were the main causes of PEP failure. In addition, immunodeficiency in a patient was another cause of failure. Our obtained data suggested that immediate precise measures after exposure based on the World Health Organization (WHO) recommendation, maintaining the temperature integrity (cold chain) of vaccines, and RIGs during transportation, and performing detailed injection schedule could prevent PEP failure in most cases. Furthermore, society’s awareness plays a key role in controlling the disease, especially in endemic areas.
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 <12 years of age, 11.8% were ≥12 to <18 years of age and 56.2% were ≥18 years of age. The entire PEP regimen was completed by 97.3% of the enrolled patients. A total of 69 AEs were reported in 64 patients. Out of these, 49 AEs in 47 patients were assessed as causally related to the study products (26 with Rabishield and 23 with Rabivax-S). The majority of the AEs were mild and all recovered without any sequelae. One serious adverse event (SAE) of fracture of the hand was reported which was not related to either Rabishield or Rabivax-S. No case of rabies was reported. Interpretation: Rabishield and Rabivax-S have an excellent safety profile and are well tolerated. No participant developed rabies during 31 day follow up. Funding: The PMS was funded by Serum institute of India Private Limited which is the manufacturer of the study products.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Rabies is a worldwide epidemic that poses a serious threat to global public health. At present, rabies in domestic dogs, cats, and some pets can be effectively prevented and controlled by ...intramuscular injection of rabies vaccine. But for some inaccessible animals, especially stray dogs, and wild animals, it is difficult to prevent with intramuscular injection. Therefore, it is necessary to develop a safe and effective oral rabies vaccine.
We constructed recombinant
(
) expressing two different strains of rabies virus G protein, named CotG-E-G and CotG-C-G, immunogenicity was studied in mice.
The results showed that CotG-E-G and CotG-C-G could significantly increase the specific SIgA titers in feces, serum IgG titers, and neutralizing antibodies. ELISpot experiments showed that CotG-E-G and CotG-C-G could also induce Th1 and Th2 to mediate the secretion of immune-related IFN-γ and IL-4. Collectively, our results suggested that recombinant
CotG-E-G and CotG-C-G have excellent immunogenicity and are expected to be novel oral vaccine candidates for the prevention and control of wild animal rabies.
Highlights • An in vitro ELISA method was tested in view of replacing the in vivo NIH test. • This ELISA is able to detect a low quantity of rabies glycoprotein in vaccines. • As the NIH test this ...ELISA is able to discriminate non compliant vaccine batches. • The monoclonal antibody recognizing the native glycoprotein is a relevant tool to appraise the potency of vaccine.
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The field distribution of the oral rabies vaccine is effective in controlling the spread of rabies. The present study aimed to investigate efficient distribution locations based on the environment, ...contact rate, and consumption by target wildlife species in South Korea. The target species (Korean raccoon dogs, domestic dogs, and feral cats) accounted for 945 contacts (52.2%), in total 1,808 contacts. There were 863 (47.8%) contacts by non-target species. Raccoon dogs, a main reservoir of rabies in South Korea, had the highest contact rate (34.1%) among all species. The contact rate by target species was highest at riparian sites and bushy mountainous vegetation, where raccoon dogs are abundant. There was remarkable contact by raccoon dogs in mountainous areas below 150 m with bushy vegetation. Our results indicate that these locations are efficient areas for vaccine distribution, especially targeting the raccoon dog. Vaccines were continuously contacted with intervals ranging from one hour to one day. Vaccines at 94.4% of the distribution points were completely consumed within two weeks. The mean consumption rate was 95.2 ± 1.93% during the overall study period. These findings suggest that the oral rabies vaccine attracts wildlife including domestic dogs and feral cats. Our results suggest that low sections of mountainous areas with bushy vegetation and/or neighboring riparian areas are rich in target wildlife species (especially raccoon dogs) and are efficient locations for vaccine distribution to control rabies in South Korea.
Abstract Background Rabies is a fatal disease where post-exposure prophylaxis (PEP) is crucial in preventing infection. However, deaths even after appropriate PEP, have been reported. The PIKA Rabies ...vaccine adjuvant is a TLR3 agonist that activates B and T cells leading to a robust immune response. Methods We conducted a phase I, open label, randomized study in healthy adults to assess the safety and immunogenicity of the PIKA Rabies vaccine and an accelerated vaccine regimen. Thirty-seven subjects were randomized into 3 groups: control vaccine classic regimen, PIKA vaccine classic regimen and PIKA vaccine accelerated regimen. Subjects were followed up for safety, rabies virus neutralizing antibodies (RVNA) and T cell responses. Results Both the control and PIKA Rabies vaccine were well tolerated. All adverse events (AEs) were mild and self-limiting. Seventy-five percent of subjects in the PIKA accelerated regimen achieved a RVNA titer ⩾0.5 IU/mL on day 7, compared to 53.9% in the PIKA classic regimen (p = 0.411) and 16.7% in control vaccine classic regimen (p = 0.012). The PIKA rabies vaccine elicited multi-specific rabies CD4 mediated T cell response already detectable ex vivo at day 7 after vaccination and that was maintained at day 42. Conclusion The investigational PIKA rabies vaccine was well tolerated and more immunogenic than the commercially available vaccine in healthy adults. Clinical trial registry: The study was registered with clinicaltrials.gov NCT02657161.
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