Delayed emergence of bovine leukemia virus after vaccination with a protective cytotoxic T cell-based vaccine

In a previous study eight MHC class I-matched sheep were vaccinated with a minimal cytotoxic T lymphocyte (CTL) peptide epitope vaccine and were chall enged with the retrovirus, bovine leukemia virus (BLV). Half the vaccinated animals remained PCR negative after challenge, whereas the remaining half and the placebo group became PCR positive within 4 weeks postchallenge (His lop AD, Good MF, Mateo L, Gardner J, Gatei MH, Daniel RCW, Meyers BV, Lavin MF, and Suhrbier A: Nat Med 1998; 4: 1193). Here we show that neither epit ope mutations nor processing differences explained why half the peptide-vac cinated animals failed to resist the BLV challenge. However, in these anima ls the development of BLV-induced lymphosarcomas was significantly delayed compared with the placebo group, suggesting a role for CTLs in preventing r etrovirus-induced cancers. Importantly, two of the initially protected anim als become PCR positive after similar to1.5 years, indicating extended supp ression but not elimination of challenge virus by vaccine-induced CTLs. The late emergence of virus could not be explained by epitope escape mutations or the loss of memory CTL responses. We speculate that high levels of effe ctor CTL may be needed to protect animals from a postchallenge viremia and maintenance of such effector CTLs, rather than memory CTLs, may be required to prevent subsequent emergence of virus from latent pools.