Research on the rabies and rabies vaccines
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Rabies is a highly lethal disease with a long history that most of the patients were infected by dog bites. Therefore, the scientific popularization and research of rabies are particularly important. This article mainly analyzes rabies from three aspects: the rabies virus, the rabies vaccines and treatment methods. Firstly, the infection mode and characteristics of the rabies virus and some clinical features after human infection with the rabies virus were analyzed, so as to facilitate people's understanding of the infection route and reduce the infection rate. The introduction of clinical features also made it easier for doctors or relatives of patients to determine whether patients were infected with rabies. Enable patients to get effective treatment quickly. The rabies vaccine is the main measure to prevent rabies. This part lists the history of human rabies vaccines and introduces some successful human rabies vaccines. Finally, the current treatment status of rabies is introduced, the methods that may play an important role in the treatment of rabies in the future are proposed, and the possibility of rabies being cured is confirmed. However, due to the complex mechanism of rabies itself, it is still necessary to continue to study rabies in order to completely defeat this disease.Keywords:
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To the Editor.
—I was surprised to see the article entitled "Human Rabies Despite Treatment With Rabies Immune Globulin and Human Diploid Cell Rabies Vaccine—Thailand" in the LEADS FROM THE MMWR in the Jan 1 issue ofJAMA.1Development of rabies despite treatment is not a rare occurrence. In Choomkasien and Wasi's2review of 707 cases of human rabies deaths between 1979 and 1986 in Thailand, 7% of the patients who died had completed a full vaccine course following exposure. Of this 7%, there were nine patients who appeared to represent failures of tissue-culture vaccines. All nine had completed the full course of vaccine. Five had received human diploid cell rabies vaccine, three had received purified chick embryo cell rabies vaccine, and one had received purified VERO cell rabies vaccine. Of these nine patients, three patients had received equine rabies immune globulin and one had received human rabiesDuck embryo vaccine
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In Europe, the elimination of wildlife rabies using oral rabies vaccination [ORV] of foxes for more than 30 years has been a success story. Since a comprehensive review on the scope of the different oral rabies vaccine baits distributed across Europe has not been available yet, we evaluated the use of different vaccine baits over the entire period of ORV [1978–2014]. Our findings provide valuable insights into the complexity of ORV programs in terms of vaccine related issues. More than 10 oral vaccines against rabies were used over the past four decades. Depending on many factors, the extent to which oral rabies virus vaccines were used varied considerably resulting in huge differences in the number of vaccine doses disseminated in ORV campaigns as well as in large spatial and temporal overlaps. Although vaccine virus strains derived from the SAD rabies virus isolate were the most widely used, the success of ORV campaigns in Europe cannot be assigned to a single oral rabies virus vaccine alone. Rather, the successful elimination of fox rabies is the result of an interaction of different key components of ORV campaigns, i.e. vaccine strain, vaccine bait and strategy of distribution.
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Several strategies are being examined to enhance the potency of DNA rabies vaccine (DRV) so that it can be used for both prophylaxis and postexposure therapy of rabies. In this study, we report a novel combination rabies vaccine (CRV) containing a low dose of cell culture-derived inactivated rabies virus vaccine and DRV. Mice immunized with CRV develop higher levels of rabies virus-neutralizing antibodies (RVNA) than those immunized with DRV and are completely protected against peripheral as well as intracerebral rabies virus challenge. The quantity of inactivated rabies virus vaccine required for enhancing the potency of DRV can be 625-fold lower than that of a standard dose of inactivated rabies virus vaccine. CRV induces higher levels of RVNA than DRV in cattle as well. Thus, we demonstrate for the first time that coinoculation of DNA vaccine and a low dose of inactivated virus vaccine can be developed into a novel cost-effective vaccination strategy for combating rabies in particular, and infectious diseases in general.
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Journal Article A Recombinant Human Adenovirus Vaccine against Rabies Get access Ludvik Prevec, Ludvik Prevec Reprints and correspondence: Dr. L. Prevec, Department of Biology, LSB429, McMaster University, Hamilton, Ontario, Canada L8S 4K1. Search for other works by this author on: Oxford Academic PubMed Google Scholar James B. Campbell, James B. Campbell Search for other works by this author on: Oxford Academic PubMed Google Scholar Brian S. Christie, Brian S. Christie Search for other works by this author on: Oxford Academic PubMed Google Scholar Larry Belbeck, Larry Belbeck Search for other works by this author on: Oxford Academic PubMed Google Scholar Frank L. Graham Frank L. Graham Search for other works by this author on: Oxford Academic PubMed Google Scholar The Journal of Infectious Diseases, Volume 161, Issue 1, January 1990, Pages 27–30, https://doi.org/10.1093/infdis/161.1.27 Published: 01 January 1990 Article history Received: 08 April 1989 Revision received: 10 August 1989 Published: 01 January 1990
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Rabies is a highly prevalent zoonotic disease and a public health threat worldwide. Currently licensed rabies vaccines are effective but less is known which would protect cattle. This study describes the construction of a novel recombinant bovine herpes virus type I (BHV-1) expressing rabies virus glycoprotein (RABV G) instead of its gE glycoprotein (gE) by CRISPR-Cas9 and homologous recombination technology (BHV-1-ΔgE-G). Insertion of the RABV G gene is stable after 20 rounds of in vitro passaging and the recombinant virus replicates to high titers in MDBK cells. The RABV G expresses in the recombinant virus-infected cells and on the virion surface of BHV-1-ΔgE-G. One single immunization with BHV-1-ΔgE-G-activated dendritic cells (DCs) and B cells furthermore induced a protective immune response in mice against severe lethal challenge infection. A protective level of RABV-specific virus-neutralizing antibody (VNA) was detected in intramuscular immunized mice and cattle without any clinical symptoms. This research demonstrated that the BHV-1 vector-based RABV vaccine is a potential candidate for cattle.
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In order to reduce the risk of allergic reactions, a purified human diploid cell culture rabies vaccine was developed. Pitman-Moore strain of rabies was propagated in WI-38 or MRC-5 cells. Both cell strains were found to be equally suitable for pro agation of rabies virus. The virus was purified and concentrated by continuous-flow sucrose density gradient ultracentrifugation. Virus peak fractions were diluted with a stabilized and then inactivated with BPL and freeze-dried. According to the standard NIH test for potency, the vaccine proved to be very potent and stable. The results of initial clinical applications of the vaccine will be presented.
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Recently travelers who were bitten by possibly rabid animals in rabies endemic regions and returned to Japan have increased in number. About half of them received rabies post-exposure prophylaxis (RPEP) with one or more doses of foreign-made rabies vaccines (FRV) in the local medical institutions. FRV, however, are not available in Japan so we have to continue the RPEP with Japanese rabies vaccine (JRV). It has not been demonstrated that an anti-rabies antibody induced with JRV following Vero cell rabies vaccine (PVRV) or chick embryo cell rabies vaccine (PCEC) could be high enough to prevent clinical rabies. We examined anti-rabies antibody (ARA) titers among the subjects visited our vaccine clinic to receive RPEP and obtained results as follows: the ARA titers after a total of 5 doses of PCEC or PVRV and JRV were high enough to prevent clinical rabies as after 5 doses of JRV. However, ARA titers obtained after receiving one dose of PVRV and 2 doses of JRV seemed lower than those produced after one dose of PCEC and 2 doses of JRV or 3 doses of JRV. To accelerate antibody production, consequently, the simultaneous intradermal and subcutaneous injection method of rabies vaccine may be applied to those who were bitten in their hands or head by possibly rabid animals and received only one dose of PVRV in rabies endemic regions.
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The safety and neuroallergic activity of current commercial and experimental rabies vaccine were studied by detecting the patho-histological changes in the central nervous system of laboratory animals (guinea-pigs) according to the method recommended by the World Health Organization (Gispen, 1975). Six rabies vaccines were tested in the experiments. The vaccines are as follows: lyophilized rabies vaccine - human; lyophilized rabies vaccine - veterinary; rabies vaccine U. S. P. duck embryo - human; avianized rabies vaccine - veterinary; inactivated rabies vaccine from strain Vnukov-32 - human; live cell rabies vaccine from strain Vnukovo-32 - veterinary. Patho-histological changes indicating the neuroallergic activity of the vaccines were observed in laboratory animals (varying range and intensity of these activities, to which the following vaccines were applied: lyophilized vaccine - veterinary and lyophilized rabies vaccine - human. The cell rabies vaccines from strain Vnukovo-32 were found to be safe; they can be recommended for their merits (including nonreactogenicity) to be used in veterinary practice in rabies immunoprophylaxis.
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ecent cases of human rabies imported to Eu-rope by travelers visiting India and Morocco demonstrate the relevance and value of receiving proper education regarding rabies prevention, in-cluding both preexposure vaccination and postex-posure prophylaxis, prior to leaving for canine rabies – endemic countries. 1,2 This is especially rele-vant for travelers planning on visiting countries in Asia and Africa where the majority of human rabies cases occur. 3 Modern cell culture vaccines recommended by the World Health Organization (WHO), including purifi ed chick embryo cell vac-cine (PCECV), purifi ed Vero cell rabies vaccine, and human diploid cell rabies vaccine (HDCV), provide a safe means by which travelers can be pro-tected in the event of exposure to rabies virus. These vaccines have been licensed for several decades, but there are limited published data regarding the length of time after a person has received his or her primary rabies vaccination, for which they will continue to develop an anamnestic response after a booster dose of rabies vaccine has been adminis-tered. 4,5 The vaccination recommendations for a person who has been vaccinated previously with a cell culture rabies vaccine and is subsequently exposed to a rabid animal include the administra-tion of two booster doses of vaccine (one dose on day 0 and the other on day 3) without the adminis-tration of rabies immunoglobulin (RIG). However, the limited amount of available data has led to some confusion regarding booster recommendations in previously vaccinated persons who are subse-quently exposed to rabid animals. 6,7 To determine how long individuals would be able to mount an anamnestic response after primary vac-cination, we contacted all veterinarians who had ini-tially received PCECV as students enrolled in a clinical trial initiated in 1986. 8 The veterinarians who agreed to participate in this booster study veri-fi ed and confi rmed that they had not received a rabies booster vaccination for 14 years since the clin-ical trial was completed, and all agreed to provide their serum samples for serological evaluation before and after receiving a booster dose of rabies vaccine. In the initial clinical trial conducted in 1986, 78 individuals were vaccinated with either HDCV or PCECV intramuscularly or intradermally as a pri-mary three-dose series. 8 In 1988, 68 of the 78 subjects received a single 1.0 mL of PCECV in tramuscularly. After the booster dose in 1988, the mean titer for subjects who received intradermal dosage initially was 1,106 (range: 270 – 6,800) and for subjects who received intramuscular dosage for their initial series was 1,859 (range: 1,100 – 9,500). For comparison purposes, a reciprocal titer of 1:25 is approximately equal to a titer of 0.5 IU/mL. Fourteen years later, 15 of those who initially received PCECV and a dose of intramuscular booster 1 year after their primary se-ries and who had not received any additional rabies vaccination since the 1988 booster were enrolled in this study. After approval of the study by the ethics committee and obtaining informed consent from the subjects, a blood sample was obtained and a single
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