Hcv Core/Ns3 Protein Immunization With “N-Terminal Heat Shock Gp96 Protein (Rnt (Gp96))” Induced Strong and Sustained Th1-Type Cytokines in Immunized Mice Publisher



Hajikhezri Z¹ ; Roohvand F² ; Maleki M³ ; Shahmahmoodi S^{1, 4} ; Amirzargar AA^{5, 6} ; Keshavarz A¹ ; Seyed N⁷ ; Farahmand M¹ ; Samimirad K¹ Show Affiliations
Source: Vaccines Published:2021

Abstract

Feeble cellular responses induced by T cell-based vaccines are a major challenge for the development of an effective vaccine against Hepatitis C virus (HCV) infection. To address this challenge, the potential of N-terminal fragment of gp96 heat shock protein (rNT (gp96) as an adjuvant was evaluated and compared to that of the CpG (as a recognized Th1-type adjuvant) in the formulation of HCV core/NS3 antigens in three immunization strategies of protein/protein, DNA/DNA, and DNA/protein. Immunized mice were evaluated for elicited immune responses in week 3 (W3) and 11 post-immunizations. Our results demonstrated that the protein (subunit) vaccine formulated with rNT (gp96) in protein/protein strategy (core/NS3 + gp96) was significantly more efficient than CpG oligodeoxynucleotides (CpG ODN) formulation and all other immunization strategies in the induction of Th1-type cytokines. This group of mice (core/NS3 + gp96) also elicited a high level of anti-Core-NS3 total immunoglobulin G (IgG) with dominant IgG2a isotype at W3. Thus, the co-administration of recombinant NT (gp96) protein with rHCV proteins might be a promising approach in the formulation of HCV subunit vaccine candidates for induction of high levels of Th1 cytokines and humoral responses. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.