394: Vaccination with Carnarypox pp65 CMV Vaccine Induces Reliable CD4+ and CD8+ T Cell Responses only in Individuals Who Lack Baseline Responses. Implications for Donor Vaccination to Boost CMV Immunity in Stem Cell Transplant Recipients

CMV reactivation after allogeniec stem cell transplant (SCT) remains a major cause of post-transplant morbidity but may be mitigated by strong T-cell responses in the transplanted donor T-cell repertoire. We vaccinated 25 subjects with “ALVAC pp-65” (sanofi pasteur, Lyon, France) to boost CMV responses in seropositive subjects and induce CMV responses in seronegative subjects. An accelerated regimen giving 1.0 ml ALVAC pp-65 on days 0 and 5 to seropositive subjects and days 0, 5, and 10 to seronegative individuals was used. CD4+ and CD8+ T-cell responses to a CMV pp65 peptide library were measured at serial timepoints post vaccination using flow cytometry to identify interferon-gamma producing T-cells. Positive responses were defined as a twofold increase of interferon-gamma production compared to unstimulated cells. Of the 25 subjects analyzed, 13 were seropositive and 12 were seronegative. As previously reported, serostatus did not correlate with baseline CD4+ and CD8+ CMV response. Indeed there were no differences in T-cell response patterns according to serostatus. We therefore segregated subjects into baseline CD4+ or CD8+ responders or non-responders irrespective of serostatus. Six of 9 CD4+ non-responders had a 2–8 fold (median 4) increase in response by day 5. In contrast, 13 of 16 subjects with a baseline CD4 response (identified by a stimulation index of ≥2 at baseline) showed decreased or undetectable responses at day 5 with variable responses thereafter. Nine of 11 CD8+ non-responders had a 2–9 fold (median 3) response by day 5. In contrast, 10 of 14 CD8+ responders showed decreased response by day 5 with variable responses thereafter. Apart from pain at the injection site, vaccine was well tolerated. These results show that ALVAC is a well tolerated vaccine with the potential to induce pp65 responses in subjects who lack baseline responses. In subjects that have baseline responses, vaccination appears to dampen immediate immune response. It is unclear if the vaccine is inducing tolerance in these individuals and if this is related to dose of the vaccine. ALVAC pp65 can elicit quick responses of varying duration in subjects that lack CD4 or CD8+ T cell responses to CMV and could therefore be used to improve the transfer of CMV immunity to SCT recipients using such donors. However, in donors that have a baseline CMV response, vaccination may be detrimental to the recipients' ability to respond to CMV.