CCR5 Ligand Levels and Immune Response to HIV Vaccines

ZRG 1 VACC (01) 4 1 R01 A152038-01
November 2001 Garzino-Demo, Alfredo
and HIVNET 26, who have received a prime (recombinant Canary pox candidate
vaccines ALVAC VCP 205 and ALVAC VCP 1452 and gpl20 boost (HIV SF2 and MN). The
limitation is that only frozen cells are available so comparison to fresh cells
will not be possible. They state they will have 20x10E6 cells available. The
question is what is the recovery and viability of these samples. They will only
get correlative data and no information on protection will be available. They
do provide information on data analysis and statistical analysis of the
correlative data that appears to be appropriate. They discuss access to samples
from future HVTN trials but these are not discussed in detail.
INNOVATION: The ability to better define the protective role of chemokines in
HIV vaccine responses is clearly important. This proposal however simply
proposes technical advances in chemokine measurement and at best correlative
data measurement in early phase vaccine trials.
INVESTIGATORS: The PI, Alfredo Garzino-Demo, is an Assistant Professor in the
Institute of Human Virology at the University of Maryland. He lists
publications relevant to the current application related to chemokine
measurements. He is well qualified to carry out the proposed studies. Dr.
Anthony DeVico, one co-investigator, is an associate professor, Institute of
Human Virology, University of Maryland. He has extensive experience in
chemokine biology as evidenced by publications and grants. He is well
qualified. Dr. George Lewis, a second co-investigator, is a professor and
director of Vaccine Research at the Institute of Human Virology, University of
Maryland, who has extensive experience in vaccine development and studies of
immune response. He is well qualified.
ENVIRONMENT: This is clearly an outstanding environment to carry out the
proposed studies. All resources are available to the PI to perform the required
experiments.
HUMAN SUBJECTS: No issues.
CRITIQUE 2:
SIGNIFICANCE: A better understanding of host factors that govern resistance to
infection with HIV or can be used, as indicators of immune status will be of
significant value in the design and evaluation of effective vaccine approaches
to block the spread of AIDS. In this proposal, the authors propose to examine
the role of chemokine receptors, such as RANTES, macrophage inflammatory
protein (MIP)-lalpha and MIP-lbeta, which potently inhibit HIV binding to the
CCR5 co-receptor, in blocking HIV infection in vitro. The authors cite several
studies that correlate the presence of higher chemokine levels with natural
higher levels of these chemokines in individuals who remain seronegative
despite high-risk exposure to HIV infection. The ability of PHA stimulated
peripheral blood mononuclear cells to release these chemokines upon stimulation
in vitro has also been shown to correlate with decreased risk of disease
progression.
This study proposes to examine the role of these chemokine levels as surrogate
markers or as predictors of HIV disease outcome. Measurement of chemokine
levels in plasma or serum is highly inaccurate, due to the tendency of these