A series of recent manuscripts by Skandorff et al., Daradoumis et al., and Ng et al. shed light on the significance of endogenous retrovirus immunity in tumor immunity and demonstrate our understanding of how to induce this immune response.

These studies address a crucial dispute in retrovirology regarding the immunological importance of the immune suppressive domain (ISD) within retroviral sequences. Skandorff and Daradoumis provide practical resolutions to this debate by examining the effects of ISD mutations on immune suppression and viral replication. Daradoumis et al. focus on full-length proteins expressed from replication deficient viral vectors to enhance T cell responses and tumor protection.

On the other hand, Skandorff et al. investigate a viral envelope without a functional ISD domain, which they reintroduce through point mutations. Both studies confirm the ability of mutated ISD to enhance the immunogenicity of full-length endogenous retrovirus proteins, particularly for T and B cell responses.

These findings highlight the critical role of endogenous retrovirus immunity and provide insights into the development of more effective live attenuated vaccines.