CCR5 Ligand Levels and Immune Response to HIV Vaccines

ZRG 1 VACC (01) 7 1 RO1 A152038-01
November 2001 Garzino-Demo, Alfredo
ligands, measurement presented in this proposal, needs to be studied. Second,
the applicant also improved a particular ELISA assay to measure different
isoforms of chemokines. However, at this point, the assay itself needs to be
validated by conducting a rigorous study in a small group of healthy and HIV
infected patients. Some of the technical steps can be worked out with samples
from many ongoing non-human primate studies before a large investment of
resources is used in human studies.
One weakness of this proposal is that it does not specify exactly how many
patient samples will be screened even though it is possible to assay as many as
possible patient samples. Because of the unknown nature of whether chemokine
measurement has any practical utility in following HIV vaccine immunized
volunteers, it would be wise to break the whole study into a few stages, with
increasing numbers of volunteer samples in each of the stages. Only when
analysis in the early stages shows promising results would the following stages
be started. In this way, limited resources can be used more efficiently.
There is another related weakness in this proposal in that it did not emphasize
the importance of a double blind approach in this critical study or the sample
size for control groups. It is also important to mention that given the nature
of phase II vaccine trials as proposed in the application, chemokine
measurement in such studies can only be linked to those receiving vaccination,
rather than to the protection provided by vaccination because protection is
usually not measured in phase-II studies.
INNOVATION: The proposed study is needed to answer important questions in
vaccine development even though the overall approach is not highly innovative.
INVESTIGATOR: The applicant is suitable for proposed study and has significant
experience in the role of chemokine in HIV infections.
ENVIRONMENT: The Institute of Human Virology is an excellent environment for
the proposed studies.
HUMAN SUBJECTS: The 6 points for human subjects were not addressed. Volunteers
will be drawn from participants in HIV Vaccine Trials Network (HVTN) studies.
GENDER, MINORITIES AND CHILDREN: Human subjects in HTVN trials are men and
women from 18-60 years of age. The minority/ethnic status of the volunteers was
not addressed and this is unacceptable for -the studies proposed.
COMMITTEE BUDGET RECOMMENDATIONS: The proposed budget is recommended in time
and amount.
NOTICE: The NIH has modified its policy regarding the receipt of amended
applications. Detailed information can be found by accessing the
following URL address: http:/7/grants.nih.gov/grants/policy/amendedapps.htm