CCR5 Ligands in HIV Vaccines

CCR5 ligands, as MDC is barely detectable at day 3, while its concentration rises at day 6 and, more robustly,
at day 9 (Fig. 4). In contrast, we could not observe increase of 1309 production by any stimulus, including
PHA (Fig. 4).
Data on cryopreserved samples are forthcoming.
In summary, our preliminary data shows that we can organize the study of a large cohort of human subject
(1), where we can measure chemokine release in response to antigen, and analyze in relationship to clinical
parameters. In addition, we have determined that chemokines are relevant to vaccination, as they are released
upon stimulation with recall antigen. In our experience, chemokine production from cells is a reproducible
parameter, so that it can be reliably used in cohort study to evaluate the impact of chemokines in the immune
response to antigen stimulation. Finally, we have shown that we can develop assays for chemokine isoforms
that are potentially relevant to HIV infection.
In conclusion, we think that these data fully support the hypothesis that chemokines release constitute a
reliable, reproducible, and informative marker of immune response that can be measured in vaccine trials and
that is equally or more sensitive than proliferative assays. Previous reports have shown that all of the subjects
immunized with canarypox-based HIV immunogen were responders when tested with a proliferation assay
similar to the one that we used (2). Since our preliminary data support the concept that chemokine assay is
equally or more sensitive than the proliferation assay, we fully expect that cell samples from 30 vaccinated
subjects and a similar number of placebo recipient will provide a sample with adequate statistical power to test
our hypotheses. For example, assuming a low 50% rate in vaccinees for MIP-lc~ and -3 and a 5% false
positive response rate in placebo recipients, we have greater than 90% power to detect these differences with a
sample of 30 vaccinees.