Truncated Core/NS3 Fusion Protein of HCV Adjuvanted with Outer Membrane Vesicles of Neisseria meningitidis Serogroup B: Potent Inducer of the Murine Immune System

Authors
Soheila Hekmat 1
Seyed Mehdi Sadat 1
Mohammad Mehdi Aslani 2
Mehdi Mahdavi 3
Azam Bolhassani 1
Fateme Asgar Halvaee 1
Seyed Mohammad Mahdi Ghahari 1
Mohammad Reza Aghasadeghi 1
Seyed Davar Siadat 4
1 Department of Hepatitis and AIDs, Pasteur Institute of Iran, Tehran, Iran
2 Department of Microbiology, Pasteur Institute of Iran, Tehran, Iran
3 Recombinant Vaccine Research Center, Tehran University of Medical Sciences, Tehran, Iran
4 Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran, Iran
10.29252/ibj.23.4.235
Abstract
Background: A licensed vaccine against hepatitis C virus (HCV) has not become available to date. The stability and antigenicity of a targeted synthesized recombinant fusion protein consisting of a truncated core and NS3 (rC/N) of HCV had been predicted. Although safe antigens, recombinant proteins are not efficacious vaccines without adjuvants. The present study evaluated the immunogenicity of rC/N as a bipartite antigen accompanied by Neisseria meningitidis serogroup B outer membrane vesicles (NMB OMVs) in BALB/c mice. Methods: The NMB OMVs were produced and evaluated accurately. The administrations were as follows: rC/N-OMV, rC/N-Freund’s complete/incomplete adjuvant (CIA), rC/N-MF59, rC/N, OMV, MF59, and PBS. The production of Th1 (IFN-γ, IL-2)/Th2 (IL-4)/Th17 (IL-17) cytokines and granzyme B (cytotoxic indicator) by splenic mononuclear cells and the humoral concentration of total IgG/IgG1 (Th2)/IgG2a (Th1) in sera of mice were measured using mouse ELISA kits. Results: Concentrations of Th1/Th2/Th17 cytokines, granzyme B, and immunoglobulins in the spleens and sera of immunized mice, which had received antigen plus each adjuvant (rC/N-OMV, rC/N-Freund’s CIA and rC/N-MF59), significantly raised compared to the controls (rC/N, OMV, MF59 and PBS). Th1-type responses were dominant over Th2-type responses in vaccinated mice with rC/N-OMV, and Th2 type responses increased dominantly in vaccinated mice with rC/N-MF59 (p < 0.05). Conclusion: NMB OMVs were able to increase Th1 immune responses dramatically more than MF59 and Freund’s CIA. The formulation of rC/N with NMB OMVs showed its ability to induce Th1, Th2, and Th17 immune responses. rC/N-NMB OMVs is a promising approach for the development of an HCV therapeutic vaccine.
Keywords
Adjuvants
Hepatitis C Virus
Immunization
Vaccines