CCR5 Ligand Levels and Immune Response to HIV Vaccines

ZRG 1 VACC (01) 6 1 RO1 AI52038-01
November 2001 Garzino-Demo, Alfredo
Specific Aim 3 is to study antigen specific release of CCR5 ligands in samples
obtained from volunteers participating in AIDS vaccine trials. Dr. Garzino-Demo
has provided letters of collaboration from investigators working on several
NIH-funded HIV Vaccine Trials, agreeing to make these cells available for these
studies. The data from the ELISA assay will be correlated to CTL activity and
ELISPOT assays, and ultimately to protection from infection. However, since
only cryopreserved cells will be available for these studies, and CTL
activities are not reliable on frozen cells, it is not clear what type of
correlations can be made or how the data will be interpreted.
INNOVATION: The methods proposed for use in these studies are standard methods
without much innovation. The ELISA assays are based on already commercially
available assays. It is not clear that ELISA assays based on simple repeats of
peptides will generate the desired specificity to detect the truncated -2RANTES
and LD78beta specifically. A number of concerns remain as to whether such
assays are likely to work as expected or that these will provide significant
data on correlation to protection from infections.
INVESTIGATOR: Dr. Garzino-Demo is a New Investigator and has not previously
held NIH grant or contract support. He is very familiar with these chemokines,
their detection, and their characterization and is one of the original authors
on the first papers on RANTES and MIP-lalpha and -beta. His collaborators, Dr.
Anthony DeVico, George Lewis and Farley Cleghorn are all well-established
investigators in the HIV Vaccine field and will provide their expertise in
immune responses to HIV Vaccine. Dr. Cleghorn will also carry out the
epidemiological/statistical analysis of the data obtained in this study. Dr.
Garzino-Demo and his team are well qualified to carry out the experiments
described in this proposal.
ENVIRONMENT: Dr. Garzino-Demo's laboratories at UMD Institute of Human Virology
are well equipped to carry out the proposed studies. He has demonstrated access
to the assays and clinical samples needed to carry out this work. However,
concerns about the reliability of these assays, especially on cryopreserved
specimens and lack of well-established basis for correlations and data
interpretation dampen the enthusiasm for the proposed work.
CRITIQUE 3:
SIGNIFICANCE: It important to investigate the immune correlates of HIV vaccine
protection. Chemokines have been proposed to play a very important role in
suppression of viral infection in HIV infected patients and may also be
important in people after immunization with HIV vaccines. Even though the exact
role of chemokines is controversial, it is important to study this question in
a population who will receive various HIV vaccines. _____
APPROACH: The approach in this study technically is quite straightforward.
There are two important aspects of this proposal. First, the applicant is going
to use an important resource, specimens from vaccinees participating in the NIH
HIV Vaccine Trial Network (HVTN) Phase I/Il Trials. The sample provided by this
network will be valuable for the study presented in this proposal, even though
many other aspects of immune responses will be measured by central labs or core
labs associated with the vaccine trial network. It is important to add
additional parameters to measure immune responses. Chemokine, especially CCR5