-
Rhode Island Medical Journal (2013) Aug 2020Rabies is an acute encephalitis that is caused by rabies virus (RABV) infection, which belongs to the Rhabdoviridae family of viruses. It causes about 59,000 human... (Review)
Review
Rabies is an acute encephalitis that is caused by rabies virus (RABV) infection, which belongs to the Rhabdoviridae family of viruses. It causes about 59,000 human deaths per year (although this number may be under-reported) and is generally fatal, once signs and symptoms begin to appear. Rabies is still very prevalent and under- reported, particularly in low to middle-income countries such as Asia and Africa, where there is lack of access to healthcare and domestic dogs are not widely vaccinated. Although not commonplace in the USA, rabies is mostly transmitted by wild animals such as bats, raccoons, skunks and foxes. Domesticated cats and dogs are also at risk of acquiring rabies, if they have not been vaccinated. Larger carnivores, such as coyotes, bobcats, mountain lions, wolves, bears, woodchucks, and beavers, should also be considered rabid (unless proven otherwise) if they are involved in an unprovoked attack on a person. The rabies vaccine can prevent 99% of deaths if administered promptly after exposure. There are two main vaccination strategies for rabies prevention: pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP). This article reviews background and epidemiology of rabies and current guidelines for rabies PrEP and PEP regimens for the United States.
Topics: Animals; Animals, Domestic; Animals, Wild; Centers for Disease Control and Prevention, U.S.; Disease Reservoirs; Humans; Population Surveillance; Rabies; Rabies Vaccines; United States; Vaccination; Zoonoses
PubMed: 32752569
DOI: No ID Found -
Revue Scientifique Et Technique... Aug 2018Current rabies vaccines are safe and, when administered properly, they are highly effective. In addition, they elicit long-lasting immunity, with virus-neutralising... (Review)
Review
Current rabies vaccines are safe and, when administered properly, they are highly effective. In addition, they elicit long-lasting immunity, with virus-neutralising antibody titres persisting for years after vaccination. However, current regimens require multiple doses to achieve high neutralising titres and they are costly, which means that it is difficult for developing countries, where rabies deaths are highest, to implement widespread vaccination. New innovations are the only way to reduce rabies disease to acceptable rates. Numerous preclinical and clinical studies are under way, testing novel vaccines, adjuvants and injection methods. Research into the use of live vaccines and alternative vaccine vectors is ongoing, while attempts to develop DNA vaccines have so far failed to match the immunogenicity and neutralising capability of traditional vaccines. The development of molecular adjuvants that induce faster, stronger immune responses with less antigen has yielded exciting preclinical results and appears to edge us closer to a better rabies vaccine. However, steep challenges remain: molecular adjuvants require administration with live vaccines, and differences in species specificity of immune molecules complicate development. Over all, the array of research undertaken over the past decade is impressive and encouraging, but most new vaccines have yet to be tested in clinical trials, and the viability of such experimental vaccines in the global market remains to be seen. Only a vaccine that outperforms currently available vaccines in every area will have a chance at widespread adoption. Nevertheless, the authors are confident that some vaccine candidates will meet these criteria.
Topics: Animals; Antibodies, Viral; Humans; Rabies; Rabies Vaccines; Vaccination
PubMed: 30747119
DOI: 10.20506/rst.37.2.2831 -
Virology Journal Nov 2022Rabies is a lethal zoonotic disease that is mainly caused by the rabies virus (RABV). Although effective vaccines have long existed, current vaccines take both time and...
Rabies is a lethal zoonotic disease that is mainly caused by the rabies virus (RABV). Although effective vaccines have long existed, current vaccines take both time and cost to produce. Messenger RNA (mRNA) technology is an emergent vaccine platform that supports rapid vaccine development on a large scale. Here, an optimized mRNA vaccine construct (LVRNA001) expressing rabies virus glycoprotein (RABV-G) was developed in vitro and then evaluated in vivo for its immunogenicity and protective capacity in mice and dogs. LVRNA001 induced neutralizing antibody production and a strong Th1 cellular immune response in mice. In both mice and dogs, LVRNA001 provided protection against challenge with 50-fold lethal dose 50 (LD) of RABV. With regards to protective efficiency, an extended dosing interval (14 days) induced greater antibody production than 3- or 7-day intervals in mice. Finally, post-exposure immunization against RABV was performed to evaluate the survival rates of dogs receiving two 25 μg doses of LVRNA001 vs. five doses of inactivated vaccine over the course of three months. Survival rate in the LVRNA001 group was 100%, whereas survival rate in the inactivated vaccine control group was only 33.33%. In conclusion, these results demonstrated that LVRNA001 induced strong protective immune responses in mice and dogs, which provides a new and promising prophylactic strategy for rabies.
Topics: Dogs; Mice; Animals; Rabies Vaccines; Rabies; RNA, Messenger; Antibodies, Viral; Rabies virus; Vaccines, Inactivated; Antibody Formation; mRNA Vaccines
PubMed: 36371169
DOI: 10.1186/s12985-022-01919-7 -
Vaccine Aug 2022A serum-free, highly purified Vero cell rabies vaccine (PVRV-NG) is under development. We previously demonstrated that pre-exposure prophylaxis (PrEP) with PVRV-NG had a... (Randomized Controlled Trial)
Randomized Controlled Trial
A serum-free, highly purified Vero cell rabies vaccine (PVRV-NG) is under development. We previously demonstrated that pre-exposure prophylaxis (PrEP) with PVRV-NG had a satisfactory safety profile and was immunogenically non-inferior to the licensed purified Vero cell rabies vaccine in adults. Here, we evaluated the safety and immunogenic non-inferiority of PrEP with PVRV-NG compared to the licensed human diploid cell vaccine (HDCV) in healthy adults (NCT01784874). Participants received three vaccinations (days 0, 7, and 28) as PrEP with or without a booster injection after 12 months. Rabies virus neutralising antibodies (RVNA) were evaluated on days 0, 28 (subgroup only), and 42, and Months 6, 12, and 12 + 14 days (booster group only). Non-inferiority (first primary objective) was based on the proportion of participants with RVNA titres ≥ 0.5 IU/mL (World Health Organization criteria for seroconversion) on day 42, expected to be ≥ 99% (second primary objective). Safety was evaluated after each dose and monitored throughout the study. At day 42, PVRV-NG was non-inferior to HDCV and the first primary objective was met; seroconversion was observed for 98.3% of PVRV-NG recipients and 99.1% of HDCV recipients. As < 99% of participants in the PVRV-NG group had RVNA titres ≥ 0.5 IU/mL, the second primary objective was not met. Booster vaccination produced a strong increase in RVNA titres for all groups, primed with PVRV-NG or HDCV. RVNA geometric mean titres tended to be higher for HDCV than PVRV-NG primary vaccine recipients. In a complementary evaluation using alternative criteria for seroconversion (complete virus neutralization at 1:5 serum dilution), 99.6% and 100% of participants in the PVRV-NG and HDCV groups, respectively, achieved seroconversion across the vaccine groups. No major safety concerns were observed during the study. PVRV-NG was well tolerated, with a similar safety profile to HDCV in terms of incidence, duration, and severity of adverse events after primary and booster vaccinations. ClinicalTrials.gov number: NCT01784874.
Topics: Adult; Antibodies, Viral; Humans; Pre-Exposure Prophylaxis; Rabies; Rabies Vaccines; Rabies virus
PubMed: 35778281
DOI: 10.1016/j.vaccine.2022.06.040 -
International Journal of Molecular... Sep 2023Inoculation routes may significantly affect vaccine performance due to the local microenvironment, antigen localization and presentation, and, therefore, final immune...
Immune Response of Inactivated Rabies Vaccine Inoculated via Intraperitoneal, Intramuscular, Subcutaneous and Needle-Free Injection Technology-Based Intradermal Routes in Mice.
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.
Topics: Animals; Mice; Mice, Inbred ICR; Rabies Vaccines; Rabies; Injections, Intramuscular; Antibodies, Neutralizing; Immunity
PubMed: 37686393
DOI: 10.3390/ijms241713587 -
Frontiers in Immunology 2023Rabies 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...
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 , and its immunogenicity and protective efficacy against live virus was evaluated in mice.
RESULTS
A two-dose vaccination with 1 μg 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 μg 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) revealed that the potency of RV021 at 15 μg/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.
Topics: United States; Animals; Humans; Mice; Rabies; Rabies Vaccines; Antibodies, Viral; Antibodies, Neutralizing; Rabies virus
PubMed: 37954577
DOI: 10.3389/fimmu.2023.1288879 -
Vaccine Oct 2019Prompt provision of post-exposure-prophylaxis (PEP) including vaccines and rabies immunoglobulin (RIG) to persons bitten by suspect rabid dogs is a key strategy to...
Prompt provision of post-exposure-prophylaxis (PEP) including vaccines and rabies immunoglobulin (RIG) to persons bitten by suspect rabid dogs is a key strategy to eliminating human deaths from dog-mediated rabies in Kenya by 2030. We assessed the availability, forecasting and supply chain logistics for rabies PEP in Kenya, compared with the system used for vaccines in the expanded program of immunization (routine vaccines). Semi-structured questionnaires capturing data on forecasting, procurement, distribution, cold chain and storage, monitoring and reporting for routine vaccines and rabies vaccines and RIG were administered to 35 key personnel at the national, county, sub-county and health facility levels in five counties. Results showed large variability in PEP availability (stockouts ranged from 3 to 36 weeks per year) with counties implementing rabies elimination activities having shorter stockouts. PEP is administered intramuscularly using the 5-dose Essen regimen (day 0, 3, 7, 14 and 28). PEP costs to bite patients were reported to range from 10 to 15 US dollars per dose; RIG was seldom available. A less robust supply and logistics infrastructure is used for rabies PEP compared to routine vaccines. Forecasting and monitoring mechanisms for rabies PEP was poor in the study counties. The supply of vaccines from the national to the sub-national level is mainly through two government agencies and a private agency. Since government decentralization, the National Vaccine and Immunization Program has remained as the main supplier of the routine vaccines, playing a lesser role in the supply of rabies biologicals. Adoption of the dose-saving intradermal route for PEP administration, reduction of PEP costs to patients, and placing rabies vaccines within the routine vaccines supply and logistics system would significantly improve PEP availability and accessibility to persons at risk of rabies; a critical step to achieving elimination of human deaths from rabies.
Topics: Health Services Accessibility; Humans; Immunoglobulins; Immunologic Factors; Kenya; Organization and Administration; Post-Exposure Prophylaxis; Rabies; Rabies Vaccines; Surveys and Questionnaires
PubMed: 31326251
DOI: 10.1016/j.vaccine.2019.05.035 -
Viruses Jan 2022Oral rabies vaccines (ORVs) have been in use to successfully control rabies in wildlife since 1978 across Europe and the USA. This review focuses on the potential and... (Review)
Review
Oral rabies vaccines (ORVs) have been in use to successfully control rabies in wildlife since 1978 across Europe and the USA. This review focuses on the potential and need for the use of ORVs in free-roaming dogs to control dog-transmitted rabies in India. Iterative work to improve ORVs over the past four decades has resulted in vaccines that have high safety profiles whilst generating a consistent protective immune response to the rabies virus. The available evidence for safety and efficacy of modern ORVs in dogs and the broad and outspoken support from prominent global public health institutions for their use provides confidence to national authorities considering their use in rabies-endemic regions. India is estimated to have the largest rabies burden of any country and, whilst considerable progress has been made to increase access to human rabies prophylaxis, examples of high-output mass dog vaccination campaigns to eliminate the virus at the source remain limited. Efficiently accessing a large proportion of the dog population through parenteral methods is a considerable challenge due to the large, evasive stray dog population in many settings. Existing parenteral approaches require large skilled dog-catching teams to reach these dogs, which present financial, operational and logistical limitations to achieve 70% dog vaccination coverage in urban settings in a short duration. ORV presents the potential to accelerate the development of approaches to eliminate rabies across large areas of the South Asia region. Here we review the use of ORVs in wildlife and dogs, with specific consideration of the India setting. We also present the results of a risk analysis for a hypothetical campaign using ORV for the vaccination of dogs in an Indian state.
Topics: Administration, Oral; Animals; Animals, Wild; Antibodies, Viral; Dog Diseases; Dogs; India; Mass Vaccination; Rabies; Rabies Vaccines; Rabies virus; Vaccination
PubMed: 35062358
DOI: 10.3390/v14010155 -
Bulletin of the World Health... Mar 2017To review the safety and immunogenicity of pre-exposure rabies prophylaxis (including accelerated schedules, co-administration with other vaccines and booster doses),... (Review)
Review
OBJECTIVE
To review the safety and immunogenicity of pre-exposure rabies prophylaxis (including accelerated schedules, co-administration with other vaccines and booster doses), its cost-effectiveness and recommendations for use, particularly in high-risk settings.
METHODS
We searched the PubMed, Centre for Agriculture and Biosciences International, Cochrane Library and Web of Science databases for papers on pre-exposure rabies prophylaxis published between 2007 and 29 January 2016. We reviewed field data from pre-exposure prophylaxis campaigns in Peru and the Philippines.
FINDINGS
Pre-exposure rabies prophylaxis was safe and immunogenic in children and adults, also when co-administered with routine childhood vaccinations and the Japanese encephalitis vaccine. The evidence available indicates that shorter regimens and regimens involving fewer doses are safe and immunogenic and that booster intervals could be extended up to 10 years. The few studies on cost suggest that, at current vaccine and delivery costs, pre-exposure prophylaxis campaigns would not be cost-effective in most situations. Although pre-exposure prophylaxis has been advocated for high-risk populations, only Peru and the Philippines have implemented appropriate national programmes. In the future, accelerated regimens and novel vaccines could simplify delivery and increase affordability.
CONCLUSION
Pre-exposure rabies prophylaxis is safe and immunogenic and should be considered: (i) where access to postexposure prophylaxis is limited or delayed; (ii) where the risk of exposure is high and may go unrecognized; and (iii) where controlling rabies in the animal reservoir is difficult. Pre-exposure prophylaxis should not distract from canine vaccination efforts, provision of postexposure prophylaxis or education to increase rabies awareness in local communities.
Topics: Age Factors; Animals; Bites and Stings; Chiroptera; Cost-Benefit Analysis; Developing Countries; Dogs; Health Services; Humans; Immunization Programs; Immunization Schedule; Models, Econometric; Peru; Philippines; Rabies Vaccines; Risk Factors; Time Factors
PubMed: 28250534
DOI: 10.2471/BLT.16.173039 -
Journal of Preventive Medicine and... Mar 2021Louis Pasteur is the renowned chemist and microbiologist of the 19th century involved in the development of the rabies vaccine. He worked with a researchers team in the...
Louis Pasteur is the renowned chemist and microbiologist of the 19th century involved in the development of the rabies vaccine. He worked with a researchers team in the laboratory, mainly Pierre Paul Emile Roux, and also physicians in the clinical practice approach and the defense of Pasteur's anti-rabies technique in the Académie Nationale de Médecine, Alfred Vulpian being the most notable. Pasteur's first studies on rabies are noted in his 1881 publication. But in 1885, he revealed that he had already immunized 50 dogs against rabies. Meanwhile, he was looking for human subjects. The most polemic of this search involves the second and last Emperor of Brazil, Dom Pedro II, who was a patron of the arts and sciences and followed and supported the work of the great scientist. During the reign of Dom Pedro II, the first Pasteur's Institute was founded in Rio de Janeiro, nine months before the Parisian, which had the financial support of Dom Pedro. This article deals with the interaction between the two outstanding characters, especially in the development of prophylactic treatment against rabies, and with the utilitarian aspects of this vaccine researches development against individual autonomy.
Topics: Animals; Brazil; Dogs; Famous Persons; History, 19th Century; Humans; Rabies; Rabies Vaccines
PubMed: 34322641
DOI: 10.15167/2421-4248/jpmh2021.62.1.1631