Rabies virus 11292 The virus is usually present in the nerves and saliva of a symptomatic rabid animal. The route of infection is usually by a bite. The infected animal is often exceptionally aggressive. Transmission may also occur via an aerosol through mucous membranes. After a typical human infection by bite, the virus enters the peripheral nervous system. It then travels along the nerves towards the central nervous system. Once the virus reaches the brain, it rapidly causes encephalitis. Rabies may also inflame the spinal cord producing myelitis (Wiki: Rabies). Rabies Most animals can be infected by the virus and can transmit the disease to humans. Infected bats, monkeys, raccoons, foxes, skunks, cattle, wolves, dogs or cats provide the greatest risk to humans. Rabies may also spread through exposure to infected domestic farm animals, groundhogs, weasels and other wild carnivores. Rodents (mice, squirrels etc) are seldom infected (Wiki: Rabies). Rabies virus is a member of the Lyssavirus genus. The virus has a bullet-like shape with a length of about 180 nm and a cross-sectional diameter of about 75 nm (Wiki: Rabies). Baboon Papio cynocephalus 9556 Bank vole Clethrionomys glareolus 447135 Bear Ursus americanus 9643 Birds Passeroidea 175121 Brown Trout Salmo trutta 8032 Buffalo Bison bison 9901 Carnivores Vulpes 9625 Cat Felis catus 9685 Catfishes Siluriformes 7995 Cattle Bos taurus 9913 Chicken Gallus gallus 9031 Chimpanzee Pan troglodytes 9598 chinchillas Chinchillidae 10150 Copper Pheasant Syrmaticus soemmerringii 9067 Deer Cervus elaphus 9860 Deer mouse Peromyscus maniculatus 10042 Dog Canis familiaris 9615 Ducks Anas 8835 Ferret Mustela putorius furo 9669 Fish Hyperotreti 117565 Gerbil Gerbillina 10045 Goat Capra hircus 9925 Gray wolf Canis lupus 9612 Guinea pig Cavia porcellus 10141 Hamster Mesocricetus auratus 10036 Horse Equus caballus 9796 Human Homo sapiens 9606 Macaque Macaca fascicularis 9541 Mongolian Gerbil Meriones unguiculatus 10047 Monkey Platyrrhini 9479 Mouse Mus musculus 10090 None None Parrot Psittacidae 9224 Pig Sus scrofa 9823 Rabbit Oryctolagus cuniculus 9986 Rainbow trout Oncorhynchus mykiss 8022 Rat Rattus 10114 Raven Corvus corax 56781 sei whale Balaenoptera borealis 9768 Sheep Ovis aries 9940 Squirrel Spermophilus richardsonii 37591 Tree shrew Tupaiidae 9393 Trouts, salmons & chars Salmoninae 504568 Turkey Meleagris gallopavo 9103 Vole Microtus ochrogaster 79684 Water buffalo Bubalus bubalis 391902 AdC68- rabies virus glycoprotein VO_0004630 Recombinant vector vaccine Research [Ref3084:Xiang et al., 2014] Intramuscular injection (i.m.) Chimpanzee adenovirus (Ad) vector serotype SAd-V24, also termed AdC68, expressing the rabies virus glycoprotein (Xiang et al., 2014). Intramuscular injection (i.m.) Recombinant vector construction A plasmid vector, termed pSG5rab.gp, that expresses the rabies virus glycoprotein under the control of an SV40 early promoter (Xiang et al., 1994). An AdC vector control was used at 10^11 vp. A commercially available human diploid cell rabies vaccine (HDCV), used intramuscularly at the recommended dose for pre-exposure vaccination, was included. The AdC vector vaccine was only given once, and the HDCV was given three times on days −41, −27 and −20 in relation to the AdC vaccine (Xiang et al., 2014). VO_0003057 The immunization resulted in sustained titers of rabies virus neutralizing antibodies and protection against a lethal rabies virus challenge infection in a non-human primate model (Xiang et al., 2014). Animals were challenged at 18 weeks after the last vaccine dose with ~10^6.4 (MICLD)50/ml as calculated via the Spearman–Kaerber method, of a virulent street strain of canine rabies virus (Xiang et al., 2014). ALVAC-rabies VO_0004639 Recombinant vector vaccine Research Intramuscular injection (i.m.) Intramuscular injection (i.m.) ALVAC-RV VO_0004728 Recombinant vector vaccine Research Intramuscular injection (i.m.) A non-adjuvanted feline rabies vaccine developed using the canarypoxvirus vector (Jas et al., 2012). Intramuscular injection (i.m.) Seronegative cats were vaccinated at 12 weeks of age and received a booster vaccination one year later (Jas et al., 2012). VO_0000287 This vaccination regimen induced a strong and sustained antibody response, and all vaccinated animals were protected against virulent rabies challenge carried out 3 years after vaccination (Jas et al., 2012). The cats were challenged by inoculation of 1 mL of rabies virus in the neck muscles (0.5 mL on the left and right side of the spine). The inoculum was a homogenate of salivary glands of foxes and each cat received 10^7.7 mouse Lethal Dose 50, the equivalent of 10^6.8 CCID50. BV-RVG/RVG VO_0004651 Recombinant vector vaccine Research Intramuscular injection (i.m.) Recombinant baculovirus (BV-RVG/RVG) was pseudotyped with the rabies virus glycoprotein (RVG) and also simultaneously expressed another RVG under the control of the immediate early CMV promoter (Wu et al., 2014). Intramuscular injection (i.m.) Recombinant protein preparation The recombinant baculovirus (BV-RVG/RVG) was pseudotyped with the rabies virus glycoprotein (RVG) and also simultaneously expressed another RVG under the control of the immediate early CMV promoter (Wu et al., 2014). Mice were immunized intramuscularly with 1 × 10^8 IFU of BV-VSVG/EGFP, BVRVG/EGFP, or BV-RVG/RVG at 3-week interval (Wu et al., 2014). VO_0003057 Mice immunized with BV-RVG/RVG developed higher levels of virus-neutralizing antibodies, and conferred 100% protection against rabies viral challenge (Wu et al., 2014). Mice were challenged intracerebrally with 50 mouse 50% lethal doses (50 LD50) of rabies virus CVS-24 (Wu et al., 2014). Canine Distemper-Adenovirus Type 2-Parainfluenza-Parvovirus-Rabies Modified Live & Killed Virus Vaccine (USDA: 13G9.20) Intervet Inc. VO_0002111 Live, attenuated vaccine; Inactivated or "killed" vaccine Licensed USA Canine Distemper-Adenovirus Type 2-Parvovirus-Rabies Modified Live & Killed Virus Vaccine (USDA: 13H9.20) Intervet Inc. VO_0002112 Live, attenuated vaccine; Inactivated or "killed" vaccine Licensed USA ChAd155-RG Recombinant vector vaccine Clinical trial ChAd155 Vector [Ref5954:Napolitano et al., 2020] Intramuscular injection (i.m.) The ChAd155-RG Vaccine consists of a replication-defective group C ChAd, ChAd155, expressing RG under the control of the CMV promoter. The RG sequence cloned into the ChAd155 vector is a medoid, a natural viral strain. (Napolitano et al., 2020) One dose (1 ml (5x10^10 vp)) of ChAd155-RG vaccine administered intramuscularly on Day 1, and 1 ml of matching placebo administered intramuscularly on Days 8, 15, 22. N=14 (3 sentinel, 11 non-sentinel) (Napolitano et al., 2020) Intramuscular injection (i.m.) RG vaccine antigen, RGN antigen, RNG vaccine antigens were inserted and evaluated in the CAd155 vector. (Napolitano et al., 2020) ChAdOx2 RabG Inactivated or "killed" vaccine Licensed ChAdOx2 RabG vector [Ref5961:Wang et al., 2018] Intramuscular injection (i.m.) ChAdOx2 RabG uses the chimpanzee adenovirus serotype 68 and is based upon a simian adenovirus-vectored candidate previously shown to achieve protection after a single dose in non-human primates. (Wang et al., 2018) Simple chemical adjuvant. (Wang et al., 2018) stored at -80 °C In two independent preparations results were: 1)Yield of 5.0x1012 VP / 9.0x1010 IU (P:I ratio = 54) from 5x107 cells 2)Yield of 1.9x1013 VP / 2.1x1011 IU (P:I ratio = 92) from 1.5x108 cells(Wang et al., 2018) Intramuscular injection (i.m.) Full length glycoprotein (Wang et al., 2018) CV7201 mRNA Recombinant vector vaccine Licensed Intramuscular injection (i.m.) Vaccine CV7202 is a recombinant vector vaccine composed of mRNA encoding the RABV-G from the Pasteur strain (Aldrich et al., 2021) Stored at −80 °C (Aldrich et al., 2021) 10 μg/mL(Aldrich et al., 2021) Intramuscular injection (i.m.) Rabies virus glycoprotein (RABV-G) (Aldrich et al., 2021) Feline Rhinotracheitis-Calici-Panleukopenia-Chlamydia Psittaci-Rabies Modified Live & Killed Virus, Modified Live Chlamydia Vaccine (USDA: 1619.20) Merial, Inc. VO_0001868 Live, attenuated vaccine; Inactivated or "killed" vaccine Licensed USA Feline Rhinotracheitis-Calici-Panleukopenia-Chlamydia Psittaci-Rabies Modified Live Virus and Chlamydia, Canarypox Vector Vaccine (USDA: 1619.R1) Merial, Inc. VO_0001869 Live, attenuated vaccine Licensed USA Feline Rhinotracheitis-Calici-Panleukopenia-Rabies Modified Live & Killed Virus Vaccine (USDA: 16T9.20) Intervet Inc., Merial, Inc. VO_0001870 Live, attenuated vaccine; Inactivated or "killed" vaccine Licensed USA Feline Rhinotracheitis-Calici-Panleukopenia-Rabies Modified Live Virus, Canarypox Vector Vaccine (USDA: 16T9.R0) Merial, Inc. VO_0001871 Live, attenuated vaccine Licensed USA Imovax Rabies Rabies Vaccine Imovax Sanofi Pasteur, SA VO_0000063 Inactivated or "killed" vaccine Licensed Intramuscular injection (i.m.) USA (License #1724) Imovax is a sterile, stable, freeze-dried suspension of rabies virus prepared from strain PM-1503-3M obtained from the Wistar Institute, Philadelphia, PA. This vaccine must only be used intramuscularly and as a single dose vial (FDA: Imovax). The vaccine should be stored in the refrigerator at 2°C to 8°C (35°F to 46°F). Do not freeze (FDA: Imovax). The virus strain PM-1503-3M obtained from the Wistar Institute, Philadelphia, PA, is harvested from infected human diploid cells (MRC-5 strain), concentrated by ultrafiltration and is inactivated by beta-propiolactone. One dose of reconstituted vaccine contains less than 100 mg albumin, less than 150 μg neomycin sulfate and 20 μg of phenol red indicator. The vaccine contains no preservative or stabilizer (FDA: Imovax). Intramuscular injection (i.m.) Strain PM-1503-3M obtained from the Wistar Institute, Philadelphia, PA. Seroconversion was often obtained with only one dose. With two doses one month apart, 100% of the recipients developed specific antibody (FDA: Imovax). Most common side effects reported in clinical studies included: injection site reactions, headache, nausea, abdominal pain, muscle aches and dizziness (FDA: Imovax). licensed Rabies human vaccine Generic Unknown VO_0000650 Inactivated or "killed" vaccine Licensed A generic representation of vaccines utilized to prevent rabies infection in humans, most commonly produced by inactivating the rabies virus so it cannot cause disease. These vaccines induce protective immunity without the risk of causing rabies. PIKA rabies vaccine Liaoning Yisheng Biopharma Co Inactivated or "killed" vaccine Clinical trial Intramuscular injection (i.m.) Pika is an inactivated purified rabies vaccine. (Zhang et al., 2016) TLR3 agonist(Zhang et al., 2016) The standard PIKA-RV containing 2.0 IU IPRV and 1.0 mg PIKA adjuvant was freeze-dried and reconstitute with 1.0 mL of water for injection (WFI) before use. (Zhang et al., 2016) Intramuscular injection (i.m.) Purevax Feline Rabies Purevax Feline Rabies Merial VO_0000871 Recombinant vector vaccine Licensed Intramuscular injection (i.m.) Canarypox virus-vectored vaccine Intramuscular injection (i.m.) RABAVERT Novartis Vaccines and Diagnostics VO_0000094 Inactivated or "killed" vaccine Licensed Intramuscular injection (i.m.) USA (License #1754), Canada The RABAVERT Vaccine is an inactivated, purified chick embryo cell vaccine (PCECV). It consists of lyophilized rabies virus (strain Flury LEP) that has been propagated in chicken fibroblasts, inactivated with beta-propiolactone, and concentrated and purified by centrifugation RabAvert should be stored protected from light at 2°C to 8°C (36°F to 46°F) (Rabavert). The strain Flury LEP was obtained from American Type Culture Collection as the 59th egg passage. The growth medium for propagation of the virus is a synthetic cell culture medium with the addition of human albumin, polygeline (processed bovine gelatin) and antibiotics. The virus is inactivated with beta-propiolactone, and further processed by zonal centrifugation in a sucrose density-gradient. The vaccine is lyophilized after addition of a stabilizer solution, which consists of buffered polygeline and potassium glutamate (Rabavert) Intramuscular injection (i.m.) When administered according to the recommended immunization schedule (days 0, 7, 21), 100% of subjects attained a protective titer (Rabavert). The most common side effects reported are: injection site reactions (redness, itching, and swelling), fever, and swollen lymph nodes (Rabavert). Rabies DNA Vaccine encoding Rabies virus Glycoprotein VO_0011553 DNA vaccine Research pgp.LAMP-1 [Ref1236:Kaur et al., 2010] Intramuscular injection (i.m.) Intramuscular injection (i.m.) DNA vaccine construction For the intramuscular route, mice were vaccinated with 100 µg of endotoxin-free pDNA in 200 µl of PBS/animal in the anterior quadriceps muscle, in the individual groups (DNA vaccine or vector control), 3 times at 3-wk intervals. Control mice were immunized with PBS only (Kaur et al., 2010). DNA vaccine imparted partial protection (60%) against challenge with 20 LD(50) of the challenge virus standard (CVS) strain of rabies virus (Kaur et al., 2010). For challenge studies, immunized mice were inoculated intracerebrally with 20 LD50 of the CVS strain of rabies virus 21 d after the last immunization. The challenged mice were observed for 18 d for symptoms indicative of rabies virus infection (Kaur et al., 2010). Rabies Killed Virus Vaccine (USDA: 1905.20) Wyeth, Intervet Inc., Merial, Inc. VO_0001760 Inactivated or "killed" vaccine Licensed USA Rabies Killed Virus Vaccine (USDA: 1905.21) Wyeth, Intervet Inc., Merial, Inc. VO_0001761 Inactivated or "killed" vaccine Licensed USA Rabies Killed Virus Vaccine (USDA: 1905.22) Intervet Inc. VO_0001762 Inactivated or "killed" vaccine Licensed USA Rabies Killed Virus Vaccine (USDA: 1905.23) Wyeth, Intervet Inc., Merial, Inc. VO_0001763 Inactivated or "killed" vaccine Licensed USA Rabies Killed Virus Vaccine (USDA: 1905.24) Pfizer, Inc., Merial, Inc. VO_0001764 Inactivated or "killed" vaccine Licensed USA Rabies Killed Virus Vaccine-Ehrlichia Risticii Bacterin (USDA: 4905.20) Merial, Inc. VO_0002289 Inactivated or "killed" vaccine Licensed USA Rabies Live Canarypox Vector Vaccine (USDA: 1901.R1) Merial, Inc. VO_0001765 Live vaccine Licensed USA Rabies Live Canarypox Vector Vaccine (USDA: 1901.R6) Merial, Inc. VO_0001766 Live vaccine Licensed USA Rabies Live Vaccinia Vector Vaccine (USDA: 1901.R0) Merial, Inc. VO_0001767 Live vaccine Licensed USA Rabies Vaccine Adsorbed (RVA) Rabies Vaccine Adsorbed None BioPort Corp VO_0000095 Inactivated or "killed" vaccine Licensed USA BioPort's Rabies Vaccine is effective for pre- and post-exposure indications, and is administered intramuscularly (not intradermally). However, this vaccine is no longer available for rabies postexposure or pre-exposure prophylaxis, and intradermal pre-exposure prophylaxis is no longer recommended because it is not available in the United States (Manning et al., 2008). Aluminum phosphate Rabies Vaccine Adsorbed (RVA) is an aqueous formulation of rabies virus cultured in diploid fetal rhesus lung (FRhL-2) cells, inactivated with beta-propiolactone (BPL), and adsorbed on aluminum phosphate adjuvant. The vaccine is prepared from the Kissling strain of Challenge Virus Standard (CVS) rabies virus adapted to fetal rhesus lung diploid cell culture. The inactivated virus is concentrated by adsorption onto aluminum phosphate adjuvant. Inactivated Kissling strain of Challenge Virus Standard (CVS) rabies virus. Rabies vaccine rVac-N VO_0011555 Recombinant vector vaccine Research Vaccinia virus [Ref1237:Fujii et al., 1994] Intraperitoneal injection (i.p.) Intraperitoneal injection (i.p.) Recombinant vector construction A/J 4-week-old mice were injected intraperitoneally (i.p.) on days 0 and 14 with 10^7 p.f.u, of the recombinant viruses. Control mice received equal doses of vaccinia virus recombinant vSC8 that contained no rabies virus sequences (Fujii et al., 1994). 92 % of mice given rVac-N (i.e. one animal succumbed b u t still had a prolonged lifespan) survived the challenge with rabies virus (Fujii et al., 1994). On day 21, the mice were challenged by footpad injection with 0.02 ml (20 MFPLDs0 , where MFPLDs0 represents mouse footpad 50% lethal dose) of the 1088 strain (Fujii et al., 1994). Rabies virus DNA vaccine encoding the ERA glycoprotein VO_0004372 DNA vaccine Research pCMV4 [Ref2380:Lodmell et al., 2000] Intramuscular injection (i.m.) monophosphoryl lipid A(MPL) (Lodmell et al., 2000) Intramuscular injection (i.m.) DNA vaccine construction This DNA vaccine expressed the full-length cDNA of the ERA rabies virus glycoprotein (Lodmell et al., 2000). Neutralizing antibody titers were enhanced following primary i.m. vaccination with DNA and MPL® (Lodmell et al., 2000). VO_0000286 After virus challenge, in the group of mice that were vaccinated with MPL, 4 of 6 mice with individual neutralizing antibody titers of 1:10 survived viral challenge. In addition, in the group of mice that did not receive MPL, 100% of the mice survived viral challenge after their second booster (Lodmell et al., 2000). Rabies virus DNA vaccine pCMV-intA-rabies encoding glycoprotein G VO_0004371 DNA vaccine Research pCMV-intA [Ref2268:Osorio et al., 1999] Intramuscular injection (i.m.) Intramuscular injection (i.m.) DNA vaccine construction Vector pCMV-intA expressed the rabies glycoprotein G (Osorio et al., 1999). Neutralizing antibody responses following DNA vaccination lasted at least nine months with high levels of RVNA in all i.m.-vaccinated dogs, and eleven of twelve i.d.-vaccinated cats. This suggests that a DNA rabies vaccine can induce durable and protective immune responses against rabies infection in companion animals (Osorio et al., 1999). VO_0000286 The geometric mean RVNA titer in the combined intradermal cat groups at day 289 was 341, a titer that correlates with solid protection against rabies challenge. Thus, it is reasonable to conclude that the high neutralization activity observed in the studies described here will afford protection against challenge, even though a challenge study was not performed (Osorio et al., 1999). Rabies virus DNA vaccine pSG5rab.gp VO_0004326 DNA vaccine Research pSG5 [Ref2162:Xiang et al., 1994] Intramuscular injection (i.m.) Intramuscular injection (i.m.) DNA vaccine construction Vector pSG5 expressed the rabies glycoprotein (ERA strain) (Xiang et al., 1994). Mice immunized intramuscularly with the pSG5rab.gp vector developed rabies virus glycoprotein-specific cytolytic T cells, lymphokinesecreting T helper cells of the TH1 subset, and rabies virus-neutralizing antibodies (Xiang et al., 1994). VO_0000286 Mice vaccinated with the pSG5rab.gp vector were fully protected against a subsequent challenge with rabies virus (Xiang et al., 1994). Rabies virus glycoprotein G mutant vaccine VO_0002991 Live, attenuated vaccine Research Intramuscular injection (i.m.) Intramuscular injection (i.m.) Gene mutation This glycoprotein G mutant is from Rabies virus (Wu et al., 2011). A glycoprotein G mutant is attenuated in mice (Wu et al., 2011). A glycoprotein G mutant induces protection in mice from challenge with wild type rabies virus (Wu et al., 2011). A glycoprotein G mutant is attenuated in hamsters (Wu et al., 2011). A glycoprotein G mutant induces significant protection in hamsters from challenge with wild type rabies virus (Wu et al., 2011). Rabies virus P protein mutant vaccine VO_0002992 Live, attenuated vaccine Research Intracranial immunization Intracranial immunization Gene mutation This P protein mutant is from rabies virus (Morimoto et al., 2005). A P protein mutant is attenuated in mice (Morimoto et al., 2005). A P protein mutant induces protection in mice from challenge with wild type rabies virus (Morimoto et al., 2005). Rabies Virus Vaccine pAlpha-Rab-G DNA vaccine Research pAlpha (sindbis virus replicon-based vaccine vector) [Ref5955:Saxena et al., 2008] Intramuscular injection (i.m.) A sindbis virus replicon-based DNA vaccine encoding the rabies virus glycoprotein elicits immune responses and complete protection in mice from lethal challenge. (Saxena et al., 2008) The full length rabies G gene was isolated from conventional rabies DNA vaccine, pTargeT-Rab-G. To construct replicon-based rabies DNA vaccine (pAlpha-Rab-G), the DNA fragment containing full length rabies G gene was isolated by digesting pTargeT-Rab-G with NheI and SmaI restriction endonucleases and ligated into XbaI and StuI sites of the replicon-based DNA vaccine vector, pAlpha. The replicon based rabies DNA vaccine (pAlpha-Rab-G) contained CMV promoter at 5′ end, 5′-UTR, nonstructural genes (nSP1-4), 26S subgenomic promoter, rabies G gene, 3′-UTR and polyA signal sequence. (Saxena et al., 2008) Intramuscular injection (i.m.) G (Saxena et al., 2008) DNA vaccine construction (Saxena et al., 2008) Rabies-specific seroconversion was observed in all vaccine-immunized mice except vector control and healthy control groups. Significant levels of IgG antibodies to rabies were detected in all of the mice immunized with different vaccines, but not in vector-immunized (pAlpha). Replicon-based DNA vaccine and Rabipur vaccine-immunized mice showed anti- body titres significantly higher (p < 0.05) than conventional DNA vaccine (pTargeT-Rab-G). Replicon-based rabies DNA vaccine and Rabipur vaccine-immunized mice showed VN (virus neutralizing) titres significantly higher (p < 0.05) than conventional DNA vaccine (pTargeT-Rab-G). (Saxena et al., 2008) Groups of Swiss albino mice (3–4 weeks old, each n = 10) were injected intramuscularly each with 50 µg of either replicon-based rabies DNA vaccine (pAplha-Rab-G) or conventional rabies DNA vaccine (pTargeT-Rab-G) or vaccine control (pAlpha) at one site in quadriceps muscle. One group (n = 10) of mice was immunized intramuscularly each with 100 µl (one-tenth dose) of commercial rabies vaccine, Rabipur. One group (n = 10) of mice received PBS (100µl) injection and kept as negative control group. All groups of mice received booster on day 21 post-immunization. (Saxena et al., 2008) Immunization with pAlpha-Rab-G and Rabipur provided significant complete (100%) protection against rabies virus challenge compared with pAlpha and PBS immunization (p < 0.0001 using Log rank test for comparison of survival). The conventional rabies DNA vaccine showed less (80%) protection compared to other vaccines. None of the control mice survived indicating the virulent nature of challenge virus. This experiment conclusively shows that protection by replicon-based rabies DNA vaccine against lethal rabies challenge can be brought about by inoculation with pAlpha-Rab-G plasmid and that the protective ability of this candidate vaccine is comparable with that of Rabipur. (Saxena et al., 2008) Mice immunized with either pAlpha-Rab-G or pTargeT-Rab-G or Rabipur or pAlpha or PBS were challenged with 20 LD50 dose virulent rabies virus following NIH method and their survival was monitored for 14 days post-challenge. (Saxena et al., 2008) RABIPUR Novartis Vaccines VO_0003103 Inactivated or "killed" vaccine Licensed Intramuscular injection (i.m.) Germany [Ref5964:Giesen et al., 2015] Rabipur is an inactivated vaccine produced using Flury LEP rabies virus strain grown in a culture of primary chick embryo fibroblast cells (Giesen et al., 2015) 1.0 ml/dose (Giesen et al., 2015) Intramuscular injection (i.m.) RABIVAX-S Serum Institute of India Pvt. Ltd. Inactivated or "killed" vaccine Licensed Intramuscular injection (i.m.) RABIVAX-S Is a lyophilized vaccine containing an inactivated purified rabies antigen, glycine, sucrose, and human serum albumin.(NCT03741270) 1 mL reconstituted vaccine Intramuscular injection (i.m.) Purified rabies antigen Raboral Raboral Merial VO_0000928 Recombinant vector vaccine Licensed Intramuscular injection (i.m.) Vaccinia virus recombinant(Brochier et al., 1991)(Mackowiak et al., 1999)(Rupprecht et al., 2004) Intramuscular injection (i.m.) RCN-rabies-G VO_0004693 Recombinant vector vaccine Research Intramuscular injection (i.m.) Recombinant RCN vaccine expressing the rabies-G glycoprotein (RCN/rabies-G) (Osorio et al., 2003). Intramuscular injection (i.m.) Recombinant vector construction A recombinant RCN vaccine expressing the rabies-G glycoprotein (RCN/rabies-G) (Osorio et al., 1999). The cats were vaccinated by the oral (PO), intranasal (IN), conjunctival (CO) or intranasal/conjunctival (IN/CO) route (dose: 10 plaque forming units or PFU) (Osorio et al., 2003). VO_0000287 The RVNA titers remained high when measured at six months post-vaccination, demonstrating that the recombinant vaccine administered via these routes is very efficient at inducing long-lasting immunity (Osorio et al., 2003). Because of humanitarian concerns, we did not perform rabies virus challenge on these cats. However, RVNA titers of 1:5 (0.69 log10) or greater in humans have been correlated with vaccine protection (Smith et al., 1996). Thus, it is reasonable to surmise that the high RVNA titers observed in the immunized cats could provide protection against challenge (Osorio et al., 2003). rLSDV-Rabies-gP VO_0004762 Recombinant vector vaccine Research Intramuscular injection (i.m.) Using the rabies virus glycoprotein (RG) as a model antigen, the recombinant LSDV encoding the rabies glycoprotein (rLSDV-RG) was able to express RG (Aspden et al., 2003). Intramuscular injection (i.m.) Recombinant vector construction Recombinant LSDV encoding the rabies glycoprotein (rLSDV-RG) (Aspden et al., 2003). NMRI mice (3–4 weeks, n=30 per group; South African Vaccine Producers) were inoculated intramuscularly on days 0 and 14 with either PBS (50 μl), rLSDV-RG (5×10^4 f.f.u. ml−1 in 50 μl), LSDV-wt (5×10^4 f.f.u. ml−1 in 50 μl) or Verorab (1/10 human equivalent dose in 50 μl) (Aspden et al., 2003). VO_0003057 Mice immunized with rLSDV-RG elicited levels of RV-specific cellular immunity (T-cell proliferation) comparable with those of mice immunized with a commercial inactivated rabies vaccine (Verorab; Pasteur Merieux). Most importantly, mice immunized with rLSDV-RG were protected from an aggressive intracranial rabies virus challenge (Aspden et al., 2003). On day 21, ten mice from each group were challenged intracranially with 8×10^−1 LD50, 8×10^−2 LD50 or 8×10^−3 LD50 dilution of live rabies virus (Aspden et al., 2003). rORFV-RabG VO_0004766 Recombinant vector vaccine Research Intramuscular injection (i.m.) Orf virus (ORFV) recombinant, D1701-V-RabG, expressing the rabies virus (RABV) glycoprotein (Amann et al., 2013). Intramuscular injection (i.m.) Recombinant vector construction Orf virus (ORFV) recombinant, D1701-V-RabG, expressing the rabies virus (RABV) glycoprotein that is correctly presented on the surface of infected cells without the need of replication or production of infectious recombinant virus(Amann et al., 2013). Mice were i.m. immunized once, twice, or thrice with 10^7 PFU of D1701-V-RabG in 2-week intervals. Two other groups were vaccinated three times with 10^6 PFU either i.m. or s.c (Amann et al., 2013). VO_0003057 All i.m. immunized animals, receiving one, two, or three inoculations of 10^7 PFU or three doses of 10^6 PFU, were completely protected, whereas 4 out of the 5 s.c. immunized animals survived the challenge. The D1701-V-RabG-immunized and protected mice did not reveal any harmful reaction, loss of body weight, or RABV-specific clinical signs (Amann et al., 2013). Two weeks after the last immunization, all mice were i.c. challenged with 3,000 mouse i.c. LD50 of the highly pathogenic RABV CVS-11 strain (Amann et al., 2013). SPEEDA-purified Vero cell rabies vaccine (SPEEDA PVRV) Liaoning Chengda Biology Co. Ltd Subunit vaccine Licensed Intramuscular injection (i.m.) China 6 IU per 0.5 ml dose (Yu et al., 2012) This vaccine was produced using Vero cells that were cultured in a microcarrier bioreactor.(Yu et al., 2012) Intramuscular injection (i.m.) Rabies virus (Yu et al., 2012) G Rabies virus VO_0011231 56384945 CDD:279337 11292 ? glycoprotein 7.66 55317.81 578 Rhabdovirus spike glycoprotein; pfam00974 >AAV85905.1 glycoprotein [Rabies lyssavirus] MVPQALLFVPFLGFSLCFGKFPIYTIPDKLGPWSPIDIHHLSCPNNLVVEDEGCTNLSGFSYLELKVGHI SAIKVNGFTCTGVVTEAETYTNFVGYVTTTFKRKHFRPTPDACRAAYNWKTAGDPRYEESLQNPYPDYQW LRTVRTTKESLVIISPSAADLDPYDKSLHSRVFPSGKCSGITVSSVYCSTNHDYTIWMPENPRQGMSCDI FTNSRGKRASKERKTCGFVDERGLYKSLRGSCKLKLCGVLGLRLMDGTWVAMQTSNETKWCSPDQLVNLH DFHSDEIEHLVVEELVKKREECLDALESIMTTKSVSFRRLSHLRKLVPGFGKAYTIINKTLMEAEAHYKS VRTWNEIVPSKGCLRVEGRCHPHVNGVFFNGIILGPDGHVLIPEMQSSLLQQHMELLESSVIPLMHPLAD PSTVFKEGDEAEDFVEVHFPDVHKKVSEVDLGLPNWGEYVLLSAGTLIALMLIIFLMICRRRVNRPESTQ RSLRGTEMKVSVTPQSGKFKSSWESYKSGDEARL Protective antigen A DNA vaccine based on lysosome-targeted glycoprotein of the rabies virus was evaluated in BALB/c mice. It imparted partial protection (60%) against challenge with 20 LD(50) of the challenge virus standard (CVS) strain of rabies virus [Ref1236:Kaur et al., 2010]. glycoprotein Rabies virus ERA 156446052 CDD:110007 11292 ? glycoprotein 505 laboratory stock >gi|156446052|gb|ABK27940.2| glycoprotein [Rabies virus] KFPIYTIPDKLGPWSPIDIHHLSCPNNLVVEDEGCTNLSGFSYMELKVGYILAIKMNGFTCTGVVTEAET YTNFVGYVTTTFKRKHFRPTPDACRAAYNWKMAGDPRYEESLHNPYPDYRWLRTVKTTKESLVIISPSVA DLDPYDRSLHSRVFPSGKCSGVAVSSTYCSTNHDYTIWMPENPRLGMSCDIFTNSRGKRASKGSETCGFV DERGLYKSLKGACKLKLCGVLGLRLMDGTWVAMQTSNETKWCPPDQLVNLHDFRSDEIEHLVVEELVRKR EECLDALESIMTTKSVSFRRLSHLRKLVPGFGKAYTIFNKTLMEADAHYKSVRTWNEILPSKGCLRVGGR CHPHVNGVFFNGIILGPDGNVLIPEMQSSLLQQHMELLESSVIPLVHPLADPSTVFKDGDEAEDFVEVHL PDVHNQVSGVDLGLPNWGKYVLLSAGALTALMLIIFLMTCCRRVNRSEPTQHNLRGTGREVSVTPQSGKI ISSWESHKSGGETRL Other Glycoprotein G Rabies virus 1489856 9627201 RABVgp4 M13215 NP_056796 11292 3290 4963 + mRNA 7.51 54466.92 524 >gi|9627197:3290-4963 Rabies virus, complete genome TAACATCCCTCAAAAGACTCAAGGAAAGATGGTTCCTCAGGCTCTCCTGTTTGTACCCCTTCTGGTTTTT CCATTGTGTTTTGGGAAATTCCCTATTTACACGATACCAGACAAGCTTGGTCCCTGGAGCCCGATTGACA TACATCACCTCAGCTGCCCAAACAATTTGGTAGTGGAGGACGAAGGATGCACCAACCTGTCAGGGTTCTC CTACATGGAACTTAAAGTTGGATACATCTCAGCCATAAAAATGAACGGGTTCACTTGCACAGGCGTTGTG ACGGAGGCTGAAACCTACACTAACTTCGTTGGTTATGTCACAACCACGTTCAAAAGAAAGCATTTCCGCC CAACACCAGATGCATGTAGAGCCGCGTACAACTGGAAGATGGCCGGTGACCCCAGATATGAAGAGTCTCT ACACAATCCGTACCCTGACTACCACTGGCTTCGAACTGTAAAAACCACCAAGGAGTCTCTCGTTATCATA TCTCCAAGTGTGGCAGATTTGGACCCATATGACAGATCCCTTCACTCGAGGGTCTTCCCTGGCGGGAATT GCTCAGGAGTAGCGGTGTCTTCTACCTACTGCTCCACTAACCACGATTACACCATTTGGATGCCCGAGAA TCCGAGACTAGGGATGTCTTGTGACATTTTTACCAATAGTAGAGGGAAGAGAGCATCCAAAGGGAGTGAG ACTTGCGGCTTTGTAGATGAAAGAGGCCTATATAAGTCTTTAAAAGGAGCATGCAAACTCAAGTTATGTG GAGTTCTAGGACTTAGACTTATGGATGGAACATGGGTCGCGATGCAAACATCAAATGAAACCAAATGGTG CCCTCCCGGTCAGTTGGTGAATTTGCACGACTTTCGCTCAGACGAAATTGAGCACCTTGTTGTAGAGGAG TTGGTCAAGAAGAGAGAGGAGTGTCTGGATGCACTAGAGTCCATCATGACCACCAAGTCAGTGAGTTTCA GACGTCTCAGTCATTTAAGAAAACTTGTCCCTGGGTTTGGAAAAGCATATACCATATTCAACAAGACCTT GATGGAAGCCGATGCTCACTACAAGTCAGTCAGAACTTGGAATGAGATCATCCCTTCAAAAGGGTGTTTA AGAGTTGGGGGGAGGTGTCATCCTCATGTAAACGGGGTATTTTTCAATGGTATAATATTAGGACCTGACG GCAATGTCTTAATCCCAGAGATGCAATCATCCCTCCTCCAGCAACATATGGAGTTGTTGGTATCCTCGGT TATCCCCCTTATGCACCCCCTGGCAGACCCGTCTACCGTTTTCAAGAACGGTGACGAGGCTGAGGATTTT GTTGAAGTTCACCTTCCCGATGTGCACGAACGGATCTCAGGAGTTGACTTGGGTCTCCCGAACTGGGGGA AGTATGTATTACTGAGTGCAGGGGCCCTGACTGCCTTGATGTTGATAATTTTCCTGATGACATGCTGGAG AAGAGTCAATCGATCGGAACCTACACAACACAATCTCAGAGGGACAGGGAGGGAGGTGTCAGTCACTCCC CAAAGCGGGAAGATCATATCTTCATGGGAATCATACAAGAGCGGGGGTGAGACCGGACTGTGAGAGCTGG CCGTCCTTTCAACGATCCAAGTCCTGAAGATCACCTCCCCTTGGGGGGTTCTTTTTGAAAAAAA >gi|9627201|ref|NP_056796.1| transmembrane glycoprotein G [Rabies virus] MVPQALLFVPLLVFPLCFGKFPIYTIPDKLGPWSPIDIHHLSCPNNLVVEDEGCTNLSGFSYMELKVGYI SAIKMNGFTCTGVVTEAETYTNFVGYVTTTFKRKHFRPTPDACRAAYNWKMAGDPRYEESLHNPYPDYHW LRTVKTTKESLVIISPSVADLDPYDRSLHSRVFPGGNCSGVAVSSTYCSTNHDYTIWMPENPRLGMSCDI FTNSRGKRASKGSETCGFVDERGLYKSLKGACKLKLCGVLGLRLMDGTWVAMQTSNETKWCPPGQLVNLH DFRSDEIEHLVVEELVKKREECLDALESIMTTKSVSFRRLSHLRKLVPGFGKAYTIFNKTLMEADAHYKS VRTWNEIIPSKGCLRVGGRCHPHVNGVFFNGIILGPDGNVLIPEMQSSLLQQHMELLVSSVIPLMHPLAD PSTVFKNGDEAEDFVEVHLPDVHERISGVDLGLPNWGKYVLLSAGALTALMLIIFLMTCWRRVNRSEPTQ HNLRGTGREVSVTPQSGKIISSWESYKSGGETGL Virmugen A glycoprotein G mutant in rabies virus is attenuated. After a one-dose intramuscular vaccination, the ERAg3m virus protected 100% of mice and hamsters from lethal challenge. In co-infections, using a lethal dose of street rabies virus mixed with ERAg3m, 100% of hamsters and 90% of mice survived and were protected against subsequent infection. [Ref1977:Wu et al., 2011]. P protein Flury-HEP 291220682 3L32 CDD:145910 11292 ? phosphoprotein 297 Phosphoprotein; pfam03012 >gi|291220682|gb|ADD84788.1| phosphoprotein [Rabies virus] MSKIFVNPSAIRAGLADLEMAEETVDLINRNIEDNQAHLQGEPIEVDNLPEDMRQFHLDDEKLSNLGEMV RVGEGKYREDFQMNEGEDPNLLFQSYLDNVGVQIVRQMRSGERFLKIWSQTVEEIISYVTVNFPNPPGRS SEDKSTQTTGRELKKETTSILSQRESQPSKAGMVAQVASGPPSLEWSATNEEDDLSVEAEIAHQIAESFS KKYKFPSRSSGIFLYNFEQLEMNLDDIVKEAKNVPGVTRLAHDGSKIPLRCVLGWVALANSKKFQLLVEA DKLSKIMQDDLDRYKSC Virmugen A P gene mutant is attenuated in mice and induces significant protection from challenge with wild type Rabies virus [Ref1803:Morimoto et al., 2005]. RABVgp1 nucleoprotein N Rabies lyssavirus VO_0011232 1489853 9627198 RABVgp1 M13215 NP_056793 11292 58 1481 + mRNA 6.57 47628.25 450 >NC_001542.1:58-1481 Rabies virus, complete genome TAACACCTCTACAATGGATGCCGACAAGATTGTATTCAAAGTCAATAATCAGGTGGTCTCTTTGAAGCCT GAGATTATCGTGGATCAATATGAGTACAAGTACCCTGCCATCAAAGATTTGAAAAAGCCCTGTATAACTC TAGGAAAGGCTCCCGATTTAAATAAAGCATACAAGTCAGTTTTATCATGCATGAGCGCCGCCAAACTTGA TCCTGACGATGTATGTTCCTATTTGGCGGCGGCAATGCAGTTTTTTGAGGGGACATGTCCGGAAGACTGG ACCAGCTATGGAATCGTGATTGCACGAAAAGGAGATAAGATCACCCCAGGTTCTCTGGTGGAGATAAAAC GTACTGATGTAGAAGGGAATTGGGCTCTGACAGGAGGCATGGAACTGACAAGAGACCCCACTGTCCCTGA GCATGCGTCCTTAGTCGGTCTTCTCTTGAGTCTGTATAGGTTGAGCAAAATATCCGGGCAAAGCACTGGT AACTATAAGACAAACATTGCAGACAGGATAGAGCAGATTTTTGAGACAGCCCCTTTTGTTAAAATCGTGG AACACCATACTCTAATGACAACTCACAAAATGTGTGCTAATTGGAGTACTATACCAAACTTCAGATTTTT GGCCGGAACCTATGACATGTTTTTCTCCCGGATTGAGCATCTATATTCAGCAATCAGAGTGGGCACAGTT GTCACTGCTTATGAAGACTGTTCAGGACTGGTGTCATTTACTGGGTTCATAAAACAAATCAATCTCACCG CTAGAGAGGCAATACTATATTTCTTCCACAAGAACTTTGAGGAAGAGATAAGAAGAATGTTTGAGCCAGG GCAGGAGACAGCTGTTCCTCACTCTTATTTCATCCACTTCCGTTCACTAGGCTTGAGTGGGAAATCTCCT TATTCATCAAATGCTGTTGGTCACGTGTTCAATCTCATTCACTTTGTAGGATGCTATATGGGTCAAGTCA GATCCCTAAATGCAACGGTTATTGCTGCATGTGCTCCTCATGAAATGTCTGTTCTAGGGGGCTATCTGGG AGAGGAATTCTTCGGGAAAGGGACATTTGAAAGAAGATTCTTCAGAGATGAGAAAGAACTTCAAGAATAC GAGGCGGCTGAACTGACAAAGACTGACGTAGCACTGGCAGATGATGGAACTGTCAACTCTGACGACGAGG ACTACTTCTCAGGTGAAACCAGAAGTCCGGAAGCTGTTTATACTCGAATCATAATGAATGGAGGTCGACT GAAGAGATCGCACATACGGAGATATGTCTCAGTCAGTTCCAATCATCAAGCTCGTCCAAACTCATTCGCC GAGTTTCTAAACAAGACATATTCGAGTGACTCATAAGAAGTTGAATAACAAAATGCCGGAAATCTACGGA TTGTGTATATCCATCATGAAAAAA >NP_056793.1 nucleoprotein N [Rabies lyssavirus] MDADKIVFKVNNQVVSLKPEIIVDQYEYKYPAIKDLKKPCITLGKAPDLNKAYKSVLSCMSAAKLDPDDV CSYLAAAMQFFEGTCPEDWTSYGIVIARKGDKITPGSLVEIKRTDVEGNWALTGGMELTRDPTVPEHASL VGLLLSLYRLSKISGQSTGNYKTNIADRIEQIFETAPFVKIVEHHTLMTTHKMCANWSTIPNFRFLAGTY DMFFSRIEHLYSAIRVGTVVTAYEDCSGLVSFTGFIKQINLTAREAILYFFHKNFEEEIRRMFEPGQETA VPHSYFIHFRSLGLSGKSPYSSNAVGHVFNLIHFVGCYMGQVRSLNATVIAACAPHEMSVLGGYLGEEFF GKGTFERRFFRDEKELQEYEAAELTKTDVALADDGTVNSDDEDYFSGETRSPEAVYTRIIMNGGRLKRSH IRRYVSVSSNHQARPNSFAEFLNKTYSSDS Protective antigen Mice vaccinated intraperitoneally (i.p.) with 10^7 p.f.u. of a vaccinia virus recombinant expressing either the glycoprotein (rVac-G) or nucleoprotein (rVac-N) of rabies virus 3 weeks before challenge were protected against peripheral lethal infection [Ref1237:Fujii et al., 1994]. 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