Eradicate Rabies with Mass Parental Vaccination, Human Post-Exposure Prophylaxis, and Gene Therapy: A Systematic Review

Post Exposure ◽

Pubmed Database ◽

Rabies is one of the neglected tropical diseases, almost 100% fatal, but preventable. Rabies virus causes the disease and causes about 59000 human deaths annually. The author searched the Pubmed Database at NCBI for articles on rabies disease published between 2007 and 2018. All articles are open access, free for redistribution and in English. To examine rabies virus, Seller’s test was used. In this article, references written by the author were included and relevant publications were also included. The author reviewed a rabies dog case kept at Nelwan Institution for Human Resource Development. The dog showed clinical signs such as aggressive behavior, in-appetence, and soaking in water. Currently, there are no drugs to treat rabies. Vaccination is the best way to prevent the disease. To eradicate rabies, mass vaccination in dogs, post-exposure prophylaxis, and gene therapy can be used. To prevent rabies disease, minimum 70% of the dog population should receive vaccination. Humans with category II exposure should receive rabies vaccine and rabies immunoglobulin. For treatment, in vivo experiment showed that gene therapy can eliminate rabies from the infected neurons by using rAAV-N796. To fight rabies virus, induced pluripotent cells in combination with CRISPR/Cas9 system can also be beneficial. Furthermore, it needs US$ 8.6 billion to fight rabies annually.

Eradicate Rabies with Mass Parental Vaccination, Human Post-Exposure Prophylaxis, and Gene Therapy: A Systematic Review

10.20944/preprints201805.0103.v2 ◽

2018 ◽

Author(s):

Martin L. Nelwan

Keyword(s):

Gene Therapy ◽

Human Resource Development ◽

Human Resource ◽

Clinical Signs ◽

Resource Development ◽

Post Exposure ◽

Canine Rabies ◽

Pubmed Database ◽

Aims: To review canine rabies, mass parental vaccination, human post-exposure prophylaxis, gene therapy and costs for fighting rabies. Place and Duration of Study: Department of Animal Science – Other, Nelwan Institution for Human Resource Development, Indonesia, between December 2017 and March 2018. Methodology: The author searched the Pubmed Database at NCBI for articles on rabies disease published between 2007 and 2018. All articles were open access and in English. For rabies virus examination, Seller’s test was used. In this article, references written by the author and other relevant publications were included. The author reviewed a rabies dog case kept at Nelwan Institution for Human Resource Development. Results: The dog showed clinical signs such as inappetance, urinary frequency and soaking in a small, juicy drain. Currently, to treat rabies, no drugs are available. For rabies prevention, vaccination is the best way. To eradicate rabies, mass vaccination in dogs, post-exposure prophylaxis, and gene therapy should be used.  Fort rabies disease eradication, minimum of 70% of the dog population should receive the vaccination. In addition, humans with category II exposure should receive a rabies vaccine and rabies immunoglobulin. Conclusion: To eradicate rabies, vaccinations are required. In addition, gene therapy can eliminate rabies from the infected neurons by using rAAV-N796. CRISPR/Cas9 system in combination with the MMEJ-based method. Furthermore, mass parental vaccination, post-exposure prophylaxis, and gene therapy can reduce costs in controlling rabies disease.

A retrospective descriptive analysis of rabies post-exposure prophylaxis cases in Dalian from 2016 to 2017

Epidemiology and Infection ◽

10.1017/s0950268819000785 ◽

2019 ◽

Vol 147 ◽

Author(s):

Yi Song ◽

Xiaoguang Lu ◽

Xue Jiang ◽

Weitong Zhao ◽

Zhiwei Fan ◽

...

Keyword(s):

Descriptive Analysis ◽

Clinical Signs ◽

Intradermal Injection ◽

Considerable Proportion ◽

Personal Factors ◽

Pet Dogs ◽

Post Exposure ◽

Grade Ii ◽

AbstractDalian, China, is a city free of rabies in recent 20 years, but the annual cost for rabies vaccination still brings an economic burden on society and individuals. We did a retrospective descriptive analysis to analyse the reason for this and try to find some ways to resolve it. A total of 10 028 post-exposure prophylaxis (PEP) cases were recorded from January 2016 to December 2017. According to the exposure grades, 32 cases were grade I; 7712 cases were grade II; 2284 cases were grade III. All the patients in the cases were injured by pet dogs without abnormal clinical signs, and 80% of them were home pet dogs. Fifty-two per cent of the pet dogs were vaccinated. All the dogs survived during the PEP vaccination period. The data showed that a considerable proportion of people who did not have exposure risk for rabies had received vaccination. The underlying reasons included social, medical and personal factors. So here we proposed to replace the current ‘five-course’ intramuscular injection with intradermal injection method in the cities free of rabies in China, this can not only achieve effective vaccination but also save resources and eliminate the fear of rabies from victims. Meanwhile we should strengthen communication on rabies knowledge and make a routine evaluation of rabies surveillance system to improve understanding of the risk for rabies from biting animals.

Clofazimine: A Promising Inhibitor of Rabies Virus

Frontiers in Pharmacology ◽

10.3389/fphar.2021.598241 ◽

2021 ◽

Vol 12 ◽

Author(s):

Jiajing Wu ◽

Shouchun Cao ◽

Shan Lei ◽

Qiang Liu ◽

Yinghong Li ◽

...

Keyword(s):

Rabies Virus ◽

High Throughput Screening ◽

Survival Rates ◽

Positive Control ◽

Antiviral Therapies ◽

Clinical Drugs ◽

Underlying Mechanisms ◽

With an almost 100% mortality rate, rabies virus (RABV) infection is a global concern. Limited post-exposure prophylaxis and lack of an effective treatment necessitate novel antiviral therapies against RABV. Here, using a high-throughput screening (HTS) method developed in our lab, 11 candidates with anti-RABV activity were identified from a library of 767 clinical drugs. Clofazimine (CFZ), an anti-leprosy drug, displayed an EC50 of 2.28 μM, and SI over 967 against RABV. Investigations into the underlying mechanisms revealed that CFZ targeted viral membrane fusion at the early stages of virus replication. Moreover, CFZ and Clofazimine salicylates (CFZS) exhibited elevated survival rates in vivo, compared with the positive control T-705. Thus, this study revealed CFZ as a promising drug against RABV infection.

Experimental utility of rabies virus-neutralizing human monoclonal antibodies in post-exposure prophylaxis

Vaccine ◽

10.1016/s0264-410x(01)00135-9 ◽

2001 ◽

Vol 19 (28-29) ◽

pp. 3834-3842 ◽

Cited By ~ 51

Author(s):

C.A Hanlon ◽

C.A DeMattos ◽

C.C DeMattos ◽

M Niezgoda ◽

D.C Hooper ◽

...

Keyword(s):

Monoclonal Antibodies ◽

Rabies Virus ◽

Human Monoclonal Antibodies ◽

Post Exposure ◽

In Vivo Efficacy of SYN023, an Anti-Rabies Monoclonal Antibody Cocktail, in Post-Exposure Prophylaxis Animal Models

Tropical Medicine and Infectious Disease ◽

10.3390/tropicalmed5010031 ◽

2020 ◽

Vol 5 (1) ◽

pp. 31 ◽

Cited By ~ 1

Author(s):

Tzu-Yuan Chao ◽

Shou-feng Zhang ◽

Li Chen ◽

Eric Tsao ◽

Charles E. Rupprecht

Keyword(s):

Animal Models ◽

Standard Dose ◽

Neutralizing Antibody ◽

Cost Effective ◽

Human Rabies ◽

Vaccine Response ◽

Post Exposure ◽

Rabies immune globulin (RIG) is an indispensable component of rabies post-exposure prophylaxis (PEP) because it provides passive immunity to prevent this otherwise inescapably fatal disease in Category III exposed patients. Even with decades of development, RIG products are still criticized for their high cost, lot-to-lot variation, and potential safety issues. They remain largely unattainable in most developing regions of the world, where demand is highest. In recent years, monoclonal antibodies (MAbs) have become widely accepted as safer and more cost-effective alternatives to RIG products. As an example, SYN023 is a 1:1 cocktail of two humanized anti-rabies MAbs previously shown to display extensive neutralizing capabilities. Here, we further assessed the efficacy of SYN023 in animal models of rabies, and found that SYN023 afforded protection equal to a standard dose of human RIG (HRIG) at 0.03 mg/kg in Syrian hamsters and 0.1 mg/kg in beagles. Potential interference with vaccine-induced immunity was analyzed for the MAbs at these concentrations. While individual MAbs did not interfere with vaccine response, SYN023 at dosages of 0.1 mg/kg and above resulted in reduced neutralizing antibody titers similar to HRIG. Thus, the in vivo characterization of SYN023 supports its utility in human rabies PEP as an efficacious alternative to RIG products.

Purified Vero Cell Rabies Vaccine (PVRV, Verorab®): A Systematic Review of Intradermal Use Between 1985 and 2019

Tropical Medicine and Infectious Disease ◽

10.3390/tropicalmed5010040 ◽

2020 ◽

Vol 5 (1) ◽

pp. 40 ◽

Cited By ~ 1

Author(s):

Thomas Moulenat ◽

Céline Petit ◽

Valérie Bosch Castells ◽

Guy Houillon

Keyword(s):

Systematic Review ◽

Vero Cell ◽

Rabies Virus ◽

Neutralizing Antibodies ◽

Rabies Vaccine ◽

Post Exposure ◽

Exposure Prophylaxis ◽

Rabies Prevention ◽

Rabies Vaccination

The purified Vero cell rabies vaccine (PVRV; Verorab®, Sanofi Pasteur) has been used in rabies prevention since 1985. Evolving rabies vaccination trends, including shorter intradermal (ID) regimens with reduced volume, along with WHO recommendation for ID administration has driven recent ID PVRV regimen assessments. Thus, a consolidated review comparing immunogenicity of PVRV ID regimens during pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP) is timely and beneficial in identifying gaps in current research. A search of seven databases for studies published from 1985 to November 2019 identified 35 studies. PrEP was assessed in 10 studies (n = 926) with 1–3-site, 1–3-visit regimens of up to 3-months duration. Seroconversion (rabies virus neutralizing antibodies [RVNA] ≥ 0.5 IU/mL) rates of 90–100% were reported within weeks, irrespective of regimen, with robust booster responses at 1 year (100% seroconversion rates by day 14 post-booster). However, data are lacking for the current WHO-recommended, 2-site, 1-week ID PrEP regimen. PEP was assessed in 25 studies (n = 2136) across regimens of 1-week to 90-day duration. All ID PEP regimens assessed induced ≥ 99% seroconversion rates (except in HIV participants) by day 14–28. This review confirms ID PVRV suitability for rabies prophylaxis and highlights the heterogeneity of use in the field.