The studies proposed in this application utilize a new drug/vaccine delivery system in a unique nonhuman maternal/infant primate model (baboon). This model may be well suited to study immune responses of potential HIV vaccines for interrupting perinatal transmission of HIV and other pathogens. The maternal/infant baboon model has been well studied and was shown to have many physiological and developmental similarities with humans thereby showing potential to be a clinically relevant model. The unique feature of this model is that the fetus is chronically catheterized. Sampling of blood and amniotic fluid can be collected without disturbing the normal placental circulation. Preliminary immunology studies have been performed by the applicants to standardize immune monitoring through ontological development. These studies have shown that the immune function of fetal baboon cells can be determined. The drug/vaccine deliver system, cochleates, represent stable phospholipid-calcium solid precipitates. They are spiral, """"""""jelly roll like"""""""" structures, with no internal aqueous space in which bioactive molecules can be enveloped and protected from degradation. Cochleates containing proteins, peptides, or DNA represent a subunit vaccine delivery system which may be effective orally, intranasally, and parenterally. The applicants propose to administer a series of formulations of cochleates containing Sendai (para influenza type 1) glycoproteins and a V3 loop peptide separately and co-formulated. The antigens proposed for use in this model system are well defined and characterized, and have relevant immunologic activities. However, they do not necessarily constitute ideal immunogens for preventative or therapeutic HIV vaccines. The Sendai serves as a immunomodulating agent, which may also facilitate transplacental delivery. The HIV-related immunogen is a 32 amino acid peptide of the V3 loop of HIV- 1 gp 1 60. This peptide has been chosen because it is highly immunogenic and capable of stimulating neutralizing antibodies, T-helper, and T-cytolytic activity which are all measurable in the proposed maternal/fetal baboon model.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AI042703-02
Application #
2877653
Study Section
Special Emphasis Panel (ZAI1-VSG-A (O1))
Project Start
1997-09-30
Project End
1999-09-29
Budget Start
1998-09-30
Budget End
1999-09-29
Support Year
2
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of Medicine & Dentistry of NJ
Department
Pediatrics
Type
Schools of Medicine
DUNS #
605799469
City
Newark
State
NJ
Country
United States
Zip Code
07107