Hepatology (Baltimore, Md.) · 2026
T- and B-cell-targeting DNA/MVA HCV vaccines induce strong and broad cellular and humoral immunity in mice and rhesus macaques.
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Rahman Sheikh Abdul, Gangadhara Sailaja, Gridley John, Mala Uchurappa, Elrod Elizabeth J, Bédard Nathalie, Bruneau Julie, Shoukry Naglaa H, Grakoui Arash, Amara Rama Rao
Аннотация
BACKGROUND AND AIMS: The hepatitis C virus (HCV) is a major cause of liver cirrhosis and cancer in humans, and an effective vaccine is urgently needed. Here, we evaluated the immunogenicity of a DNA prime and modified vaccinia Ankara (MVA) boost vaccine expressing H77 genotype 1a HCV immunogens to induce both T- and B-cell responses.
APPROACH AND RESULTS: The non-structural (NS) immunogens expressed NS3, NS4, and NS5. The structural plus p7 immunogen (S-p7) expressed Core, E1, E2, and p7. We tested the immunogenicity of these vaccines in mice and rhesus macaques (RMs) with 2 or 3 doses of DNA followed by 1 or 2 doses of MVA. The NS immunogens induced CD4 and CD8 T-cell responses against multiple NS proteins, with a dominant CD4 T-cell response to NS3 and NS5, and a dominant CD8 T-cell response to NS3. The S-p7 immunogen induced E2-binding IgG titer with neutralizing activity against autologous and heterologous HCV pseudovirus particles. In addition, the S-p7 immunogen induced a CD4 and CD8 T-cell response directed against E1 (0.08% and 0.09%, respectively) and E2 (0.13% and 0.18%, respectively) in RMs. Co-delivery of S-p7 and NS vaccines elicited a T-cell response against the majority of HCV proteins, which was comparable to the T-cell response observed in humans with HCV resolution.
CONCLUSIONS: These findings show that the DNA/MVA prime/boost vaccination induces a strong and broad CD4 and CD8 T-cell response to multiple HCV proteins and a neutralizing antibody response. These results aid in the development of vaccines for HCV.
APPROACH AND RESULTS: The non-structural (NS) immunogens expressed NS3, NS4, and NS5. The structural plus p7 immunogen (S-p7) expressed Core, E1, E2, and p7. We tested the immunogenicity of these vaccines in mice and rhesus macaques (RMs) with 2 or 3 doses of DNA followed by 1 or 2 doses of MVA. The NS immunogens induced CD4 and CD8 T-cell responses against multiple NS proteins, with a dominant CD4 T-cell response to NS3 and NS5, and a dominant CD8 T-cell response to NS3. The S-p7 immunogen induced E2-binding IgG titer with neutralizing activity against autologous and heterologous HCV pseudovirus particles. In addition, the S-p7 immunogen induced a CD4 and CD8 T-cell response directed against E1 (0.08% and 0.09%, respectively) and E2 (0.13% and 0.18%, respectively) in RMs. Co-delivery of S-p7 and NS vaccines elicited a T-cell response against the majority of HCV proteins, which was comparable to the T-cell response observed in humans with HCV resolution.
CONCLUSIONS: These findings show that the DNA/MVA prime/boost vaccination induces a strong and broad CD4 and CD8 T-cell response to multiple HCV proteins and a neutralizing antibody response. These results aid in the development of vaccines for HCV.