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Virology Research Journal
Volume 1 Issue 4 Vaccines World 2017
Notes:
Page 37
November 09-10, 2017 Vienna, Austria
21st World Congress and Exhibition on
VACCINES, VACCINATION & IMMUNIZATION
Immunological evaluation of HCV core and
its alternative reading frame protein vaccine
prototypes
Irina Sominskaya, Juris Jansons, Anastasija Dovbenko, Ivars Petrovskis and
Dace Skrastina
Latvian Biomedical Research and Study Center, Latvia
Hepatitis C remains a serious healthcare problem and there is
no prophylactic or therapeutic vaccine currently available,
although many candidates are in clinical trials. One of the
attractive targets is the nucleocapsid protein (core). HCV core (aa
1-191) is highly conserved among HCV genotypes. It binds and
packages viral genomic RNA and regulates its translation. The 5'
terminus of HCV genome also encodes core+1/ARF protein. This
protein possibly participates in HCV morphology or replication,
it can be important in gene regulation and it can affect immune
response mechanisms. A set of plasmids for eukaryotic and
prokaryotic expression carrying different in length variants of the
5' terminus of HCV genome were constructed. Obtained DNA
and proteins were purified and used in immunization of BALB/c
mice in different schemes of immunization by protein and naked
DNA (in vivo electroporation). Specific immune response was
determined and immunization with HCV core aa 1-159 and full
length ARFP proteins expressed in E. coli induced the specific
immune response. The antibody titers against HCV core reached
104 and maximum antibody titers against ARFP reached 103.
Immunization with HCV core and ARFP genes also induced
the specific immune response. Both natural and mutated HCV
core genes with prohibited frame-shift provide the same levels
of specific cellular responses. Thus, a higher expression of HCV
core from the mutated or optimized genes compared to the wild
type sequence could not provide for its better immunogenicity.
Efficacy of ARFP expression by the natural ribosome frameshift
mechanism was low and obviously insufficient to induce a
specific immune response. Thus, anti-ARFP immune response is
not competing with that against HCV core, and cannot explain
low immunogenicity of core in DNA-immunization performed
with the virus-derived genes. The immunization by DNA-prime
and protein-boost seems to combine the advantages of both
approaches and improve the immune response.
Recent Publications
• Sominskaya I, Jansons J, Dovbenko A, et al (2015)
Comparative immunogenicity in rabbits of the polypeptides
encoded by the 5' terminus of hepatitis C virus RNA. J
Immunol Res.
• Dishlers A, Skrastina D, Renhofa R, et al (2015)The hepatitis
B virus core variants that expose foreign C-terminal
insertions on the outer surface of virus-like particles. Mol
Biotechnol. 57(11-12):1038-49.
• Ivanov A V, Smirnova O A, Petrushanko I Y, et al (2015)
HCV core protein uses multiple mechanisms to induce
oxidative stress in human hepatoma Huh7 cells. Viruses
7(6):2745-70.
• Sominskaya I, Skrastina D, Petrovskis I, et al (2013) A VLP
library of C-terminally truncated hepatitis B core proteins:
correlation of RNA encapsidation with a Th1/Th2 switch in
the immune responses of mice. PLoS One. 8(9):e75938.
• Skrastina D, Petrovskis I, Petraityte R, et al (2013) Chimeric
derivatives of hepatitis B virus core particles carrying major
epitopes of the rubella virus E1 glycoprotein. Clin Vaccine
Immunol. 20(11):1719-28.
Biography
Irina Sominskaya has completed her Doctor of Biology Degree from Latvian
University, Riga, Latvia in 1992. She is the Head of Viral hepatitis group of
Latvian Biomedical Research and Study Center, Riga, Latvia. Using a
multidisciplinary approach, including molecular biology, cell biology, and
immunology technologies, the objective of group research is to gain a deeper
understanding of virus-host interactions at a fundamental level. She has 25
publications and was a project Leader of several Latvian and international
projects. She was supervisor of four doctoral degree students.
Irina Sominskaya et al., Virol Res J 2017, 1:4