A Rabies Composition Comprising Pika Adjuvant

Abstract

The present disclosure provides a rabies composition comprising IPRV and PIKA adjuvant, and the pharmaceutical use thereof. The present disclosure also discloses a method for prophylaxis or therapeutic treatment of rabies virus infection, the method comprises a step of administering the rabies vaccine composition to a host. The rabies composition is more stable and safe, and is able to induce earlier and higher titers of neutralizing antibody.

1 . A rabies vaccine composition, comprising:
 a) inactivated purified rabies virus (IPRV),   b) PIKA adjuvant, and   c) human serum albumin (HSA);   
       wherein
 the amount of IPRV is from 0.2 IU to 4.0 IU per unit dose, 
 the amount of PIKA adjuvant is from 250 μg to 5000 μg per unit dose, and 
 the amount of HSA is from 0.1% to 0.9% by concentration. 
 
     
     
         2 . The rabies vaccine composition according to  claim 1 , wherein the amount of said IPRV is selected from the group consisting of 0.2 IU, 0.5 IU, 1.0 IU, 1.5 IU, 2.0 IU, 2.5 IU, 3.0 IU, 3.5 IU, 4.0 IU per unit dose, and the range between any two of the following amounts: 0.2 IU, 0.5 IU, 1.0 IU, 1.5 IU, 2.0 IU, 2.5 IU, 3.0 IU, 3.5 IU, and 4.0 IU per unit dose 
     
     
         3 . The rabies vaccine composition according to  claim 2 , wherein the amount of said IPRV is from 0.5 IU to 3.0 IU per unit dose; preferably from 1.0 IU to 2.5 IU per unit dose. 
     
     
         4 . The rabies vaccine composition according to  claim 1 , wherein the amount of said PIKA adjuvant is selected from the group consisting of 250 μg, 500 μg, 1000 μg, 1500 μg, 2000 μg, 3000 μg, 4000 μg, 5000 μg per unit dose, and the range between any two of the following amounts: 250 μg, 500 μg, 1000 μg, 1500 μg, 2000 μg, 3000 μg, 4000 μg, and 5000 μg per unit dose. 
     
     
         5 . The rabies vaccine composition according to  claim 4 , wherein the amount of said PIKA adjuvant is between from 500 μg to 4000 μg per unit dose, or from 1000 μg to 3000 μg, or from 1500 μg to 2500 μg, optionally about 2000 μg per unit dose. 
     
     
         6 . The rabies vaccine composition according to  claim 1 , wherein the amount of said HSA is selected from the group consisting of 0.2%, 0.25%, 0.3%, 0.35%, 0.4%, 0.45%, 0.5%, 0.6% by concentration, and the range between any two of the following amounts: 0.2%, 0.25%, 0.3%, 0.35%, 0.4%, 0.45%, 0.5%, and 0.6% by concentration. 
     
     
         7 . The rabies vaccine composition according to  claim 1 , wherein the ratio of IPRV to PIKA adjuvant is selected from the group consisting of: 1 IU/100 μg, 1 IU/125 μg, 1 IU/200 μg, 1 IU/250 μg, 1 IU/300 μg, 1 IU/350 μg, 1 IU/400 μg, 1 IU/450 μg, 1 IU/500 μg, 1 IU/550 μg, 1 IU/600 μg, 1 IU/700 μg, 1 IU/800 μg, 1 IU/1000 μg, 1 IU/1500 μg, 1 IU/2000 μg, and the ratio between any two of the following ratios: 1 IU/100 μg, 1 IU/125 μg, 1 IU/200 μg, 1 IU/250 μg, 1 IU/300 μg, 1 IU/350 μg, 1 IU/400 μg, 1 IU/4501 μg, 1 IU/500 μg, 1 IU/550 μg, 1 IU/600 μg, 1 IU/700 μg, 1 IU/800 μg, 1 IU/1000 μg, 1 IU/1500 μg, and 1 IU/2000 μg; optionally the ratio of IPRV to PIKA adjuvant is 1 IU/500 μg. 
     
     
         8 . The rabies vaccine composition according to any of  claims 1 - 7 , wherein the amount of IPRV is 2.0 IU per unit dose, and the amount of PIKA adjuvant is 1000 μg per unit dose. 
     
     
         9 . The rabies vaccine composition according to any of  claims 1 - 8 , wherein the amount of IPRV is 2.0 IU per unit dose, the amount of PIKA adjuvant is 2000 μg per unit dose, and the amount of HSA is 0.3% by concentration. 
     
     
         10 . The rabies vaccine composition according to any of  claims 1 - 7 , wherein the amount of IPRV is 1.5 IU per unit dose, the amount of PIKA adjuvant is 2000 μg per unit dose, and the amount of HSA is 0.3% by concentration. 
     
     
         11 . The rabies vaccine composition according to any of  claims 1 - 7 , wherein the amount of IPRV is 4.0 IU per unit dose, and the amount of PIKA adjuvant is 1000 μg per unit dose, and the amount of HSA is 0.5% by concentration. 
     
     
         12 . The rabies vaccine composition according to  claim 1 , said composition further comprises pharmaceutical acceptable buffer; and the pH of said buffer is between pH 7.0 to pH 8.0. 
     
     
         13 . The rabies vaccine composition according to  claim 1 , wherein the said composition does not comprise gelatin. 
     
     
         14 . The rabies vaccine composition according to  claim 1 , wherein the said composition further comprises maltose, wherein the amount of said maltose is between 1.0% and 6.0% by concentration. 
     
     
         15 . The rabies vaccine composition according to any one of  claims 1 - 14 , wherein said IPRV is selected from the group consisting of CTN strain, PM strain, aG strain and PV strain; optionally CTN-1 strain, Pitman-Moore L503 strain or PV-2061 strain. 
     
     
         16 . The rabies vaccine composition according to  claim 1 , wherein the said IPRV is prepared in Vero cell or primary hamster kidney cell. 
     
     
         17 . The rabies vaccine composition according to any one of  claims 1 - 16 , wherein said composition is in a liquid form, optionally in solution or in suspension. 
     
     
         18 . The rabies vaccine composition according to any one of  claims 1 - 17 , wherein the concentration of said IPRV is from 0.05 IU/ml to 40.0 IU/ml. 
     
     
         19 . The rabies vaccine composition according any one of  claims 1 - 18 , wherein said unit dose is prepared into a volume which is selected from the group consisting of 0.1 ml, 0.15 ml, 0.2 ml, 0.5 ml, 1.0 ml, 1.5 ml, 2.0 ml, and any volume between any two of the following volumes: 0.1 ml, 0.15 ml, 0.2 ml, 0.5 ml, 1.0 ml, 1.5 ml, and 2.0 ml. 
     
     
         20 . A rabies vaccine composition, which is the solid form of the rabies vaccine composition according to any one of  claims 1 - 19 , optionally said solid form is lyophilized form. 
     
     
         21 . A pharmaceutical kit, comprising or consisting of:
 a) the rabies vaccine composition of any of  claims 1 - 20 ,   b) a vial,   c) an instruction for use, and   d) optionally water for injection,   
       preferably, said instruction for use suggests the following administration regimen:
 1) 2-2-1 regimen for post exposure treatment: 2 unit dose administered on days 0, 2 unit dose administered on days 3 and 1 unit dose administered on days 7 post exposure; and/or 
 2) 2-1 regimen for prophylaxis: 2 unit dose administered on days 0, and 1 unit dose administered on days 7. 
 
     
     
         22 . Use of rabies vaccine composition according to any one of  claims 1 - 20  in manufacture of a medicament for the treatment or prophylaxis of rabies virus infection. 
     
     
         23 . A method for treatment or prevention of rabies caused by rabies virus infection, the method comprises a step of administering the rabies vaccine composition of any of  claims 1  to  20  to a host, wherein said host has been exposed to rabies virus. 
     
     
         24 . A method for inducing an immune response to rabies virus infection, the method comprises a step of administering the rabies vaccine composition of any of  claims 1  to  20  to a host, wherein said host has been exposed to rabies virus. 
     
     
         25 . The method according to  claim 23  or  24 , wherein the rabies vaccine composition of any of  claims 1  to  20  is administered to a host for 5 times within 7 days post exposure of rabies virus. 
     
     
         26 . The method according to  claim 25 , wherein the rabies vaccine composition of any of  claims 1  to  20  is administered to a host based on the following regimen:
 a first administration on 0 day post exposure, 
 a second administration on 0 day post exposure, 
 a third administration on 2 or 3 day post exposure, 
 a fourth administration on 2 or 3 day post exposure, and 
 a fifth administration on 6 or 7 day post exposure, respectively. 
 
     
     
         27 . The method according to  claim 23  or  24 , wherein the rabies vaccine composition of any of  claims 1  to  20  is administered to a host based on the following regimen:
 a 1 st  and a 2 nd  administration on 0 day post exposure, 
 a 3 rd  and a 4 th  administration on 2 or 3 day post exposure, and 
 a 5 th  and/or a 6 th  administration on 7 day post exposure, respectively. 
 
     
     
         28 . A method for prophylaxis of rabies caused by rabies virus infection, the method comprises a step of administering the rabies vaccine composition of any of  claims 1  to  20  to a host, wherein said host is not exposed to rabies virus. 
     
     
         29 . A method of inducing an immune response to a rabies virus, the method comprises a step of administering the rabies vaccine composition of any of  claims 1  to  20  to a host, wherein said host is not exposed to rabies virus. 
     
     
         30 . The method according to  claim 28  or  29 , wherein the rabies vaccine composition of any of  claims 1  to  20  is administered to a host for 3 times within 7 days. 
     
     
         31 . The method according to  claim 30 , wherein the rabies vaccine composition of any of  claims 1  to  20  is administered to a host based on the following regimen:
 a first administration on day 0, 
 a second administration on day 0, and 
 a third administration on day 7, respectively. 
 
     
     
         32 . The method according to any one of  claims 23 - 29 , wherein said administration is by intramuscular injection, intradermal delivery, transdermal delivery, subcutaneous injection, parenteral injection, intraperitoneal injection, intravenous injection, inhalation, rectal delivery, nasal delivery, oral delivery, or topical delivery. 
     
     
         33 . The method according to any one of  claims 23 - 29 , wherein said host is human or non-human animal. 
     
     
         34 . The rabies vaccine composition according to any one of  claims 1 - 20  for use in a method of medical treatment, wherein the method involves administering the rabies vaccine composition five or six times within seven days. 
     
     
         35 . The rabies vaccine composition for use according to  claim 34 , wherein the method of treatment involves administering the rabies vaccine composition based on the following regimen:
 a 1 st  and a 2 nd  administration on 0 day post exposure,   a 3 rd  and a 4 th  administration on 2 or 3 day post exposure, and   a 5 th  and/or a 6 th  administration on 7 day post exposure, respectively.   
     
     
         36 . The rabies vaccine composition according to any one of  claims 1 - 20  for use in a method of prevention of rabies, wherein the method involves administering the rabies vaccine composition three times within seven days. 
     
     
         37 . The rabies vaccine composition for use according to  claim 36 , wherein the method of prevention involves administering the rabies vaccine composition base on the following regimen:
 a first administration on day 0,   a second administration on day 0, and   a third administration on day 7, respectively.