TY - JOUR
T1 - Immunization with recombinant vaccinia viruses expressing structural and part of the nonstructural region of tick-borne encephalitis virus cDNA protect mice against lethal encephalitis
AU - Dmitriev, Igor P.
AU - Khromykh, Alexander A.
AU - Ignatyev, George M.
AU - Gainullina, Margarita N.
AU - Ageenko, Valentina A.
AU - Dryga, Sergey A.
AU - Vorobyeva, Maya S.
AU - Sandakhchiev, Lev S.
N1 - Funding Information:
This work was supported in part by grant 95-04-12463a from the Rassian Foundation for Fundamental Researches. The authors are grateful to A.G. Pletnev and K.V. Pugachev for supplying cDNA clones of TBEV strain Sofin, P.F. Safronov and T.P. Mikriukova for supplying cDNA clones of TBEV strain “205”, and L.E. Matveev for anti-E monoclonal antobodies 2H3. We also thank M.H. Rasshepkina for assistance in animal protection experiments, M.Yu. Rukavishnikov for help with the
PY - 1996/1/26
Y1 - 1996/1/26
N2 - Three recombinant vaccinia viruses containing different fragments of tick-borne encephalitis virus (TBEV) cDNA representing the 5′-noncoding region (5′NCR), all structural and part of the nonstructural regions were constructed. Western blot analysis showed that E and NS1 proteins were expressed and processed correctly in cells infected with recombinant viruses vC-NS1 (coding for C-prM-E-NS1 region) and vC-NS3 (coding for C-prM-E-NS1-NS2A-NS2B-NS3 region). In contrast, in cells infected with recombinant virus v5′C-NS2A (coding for 5′NCR and C-prM-E-NS1-NS2A regions) expression of NS1 protein was greatly reduced and no E protein was detected. Immunization of mice with vC-NS3 induced high levels of TBEV-specific antibodies and protected them against intraperitoneal challenge with 107 LD50 of TBEV. The level of protection was very similar to the level of protection achieved by immunization with commercially available inactivated TBEV vaccine. Although the immunization of mice with recombinants vC-NS1 and v5′C-NS2A induced much lower levels of TBEV-specific antibodies, they were still protected against intraperitoneal challenge with 104 and 103.6 LD50 of TBEV, respectively. The high level of protection against TBEV infection achieved by the immunization of mice with the recombinant vaccinia virus vC-NS3 makes this virus a very attractive candidate for development of a live recombinant vaccine against TBEV.
AB - Three recombinant vaccinia viruses containing different fragments of tick-borne encephalitis virus (TBEV) cDNA representing the 5′-noncoding region (5′NCR), all structural and part of the nonstructural regions were constructed. Western blot analysis showed that E and NS1 proteins were expressed and processed correctly in cells infected with recombinant viruses vC-NS1 (coding for C-prM-E-NS1 region) and vC-NS3 (coding for C-prM-E-NS1-NS2A-NS2B-NS3 region). In contrast, in cells infected with recombinant virus v5′C-NS2A (coding for 5′NCR and C-prM-E-NS1-NS2A regions) expression of NS1 protein was greatly reduced and no E protein was detected. Immunization of mice with vC-NS3 induced high levels of TBEV-specific antibodies and protected them against intraperitoneal challenge with 107 LD50 of TBEV. The level of protection was very similar to the level of protection achieved by immunization with commercially available inactivated TBEV vaccine. Although the immunization of mice with recombinants vC-NS1 and v5′C-NS2A induced much lower levels of TBEV-specific antibodies, they were still protected against intraperitoneal challenge with 104 and 103.6 LD50 of TBEV, respectively. The high level of protection against TBEV infection achieved by the immunization of mice with the recombinant vaccinia virus vC-NS3 makes this virus a very attractive candidate for development of a live recombinant vaccine against TBEV.
KW - Protectivity
KW - Recombinant vaccinia virus
KW - Tick-borne encephalitis virus
KW - Vaccine candidate
UR - http://www.scopus.com/inward/record.url?scp=0030044237&partnerID=8YFLogxK
U2 - 10.1016/0168-1656(95)00141-7
DO - 10.1016/0168-1656(95)00141-7
M3 - Article
C2 - 8717392
AN - SCOPUS:0030044237
SN - 0168-1656
VL - 44
SP - 97
EP - 103
JO - Journal of Biotechnology
JF - Journal of Biotechnology
IS - 1-3
ER -