Human Ad19a/64 HERV-W Vaccines Uncover Immunosuppression Domain-Dependent T-Cell Response Differences in Inbred Mice

Area of Science:

• Immunology
• Oncology
• Virology

Background:

• Human endogenous retrovirus type W (HERV-W) expression is associated with cancer.
• HERV-W antigens are potential targets for therapeutic cancer vaccines.
• Previous studies used mutated retroviral envelopes to enhance vaccine immunogenicity.

Purpose of the Study:

• To evaluate the immunogenicity of wild-type versus mutated HERV-W envelope immunosuppressive domain (ISD) for cancer vaccine development.
• To identify the most effective HERV-W cancer vaccine candidate.

Main Methods:

• In vitro and in vivo evaluation of HERV-W envelope vaccines (wild-type and ISD-mutated).
• Assessment of murine antigen-presenting cell activation and specific T-cell responses.
• Survival analysis in mice bearing HERV-W envelope-expressing tumors.

Main Results:

• The wild-type HERV-W vaccine induced higher murine antigen-presenting cell activation and specific T-cell responses compared to the ISD-mutated vaccine.
• The wild-type HERV-W vaccine significantly increased survival probability in mice with HERV-W tumors.

Conclusions:

• Wild-type HERV-W envelope vaccines are more immunogenic and effective than ISD-mutated versions.
• These findings support the development of HERV-W-based cancer vaccines for HERV-W-positive cancers.