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163 New Immune Strategies to Reduce CCR5 Expression and Block HIV Infection

Lopalco, L; Diomede, L; Merati, V; Clemente, F; Asti, V; Pastori, C

JAIDS Journal of Acquired Immune Deficiency Syndromes: April 2011 - Volume 56 - Issue - p 69
doi: 10.1097/01.qai.0000397350.38298.53

Immunobiology of HIV Unit, Division of Immunology, Infectious Diseases and Transplantation, San Raffaele Scientific Institute, Milan, Italy

CCR5 is one the main co-receptors for HIV and the predominant one for HIV during mucosal infection which represents >95% of new infections worldwide. Antibodies against cell surface receptors can either block ligand binding or cause internalization of the receptor thus decreasing their concentration on the cell surface, either of which would block HIV-1 infection. Thus CCR5 could become an important target for therapeutic and vaccine designs.

The main objective of our vaccine approach is to overcome tolerance to “self” CCR5 epitopes to raise immune responses that will counter the expression of CCR5 on host cells. This has been achieved by the parallel testing of viral vectors, which are able to support antigen presentation of proteins and most importantly support the presentation of conformation dependent epitopes on their surface. As the achievement of strong and long-lasting antibody responses requires a careful timing of administration and a proper adjuvant formulation, especially when conformation-sensitive epitopes are targeted, we focus on specific formulations that promote humoral responses. We used a different combination of imunization routes including intraperitoneal, intranasal, intrarectal and intramuscular. Each immunization with antigens of interest has been performed in the presence of different suitable adjuvant molecules, such as Freund, RIBI, Alum and Montanide.

Preliminary results showed that the use of proper adjuvant formulation and a combination of intraperitoneal plus intranasal immunizations selectively promote CCR5 specific IgG and IgA secretion with expected properties.

Results from these studies provide essential directions for the development of a durable HIV infection prevention measure not restricted by HIV-1 isolate variability. Moreover, this strategy may be combined with other immunization modality to confer more effective protection via multiple targets.

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