Analysis of protective function and immunomodulatory effects of passive immunization against HIV and EBV in mice with reconstituted human immune system components

1. Summary of the research plan

Human immunodeficiency virus (HIV) and Epstein Barr virus (EBV) interact in nearly all HIV positive individuals, because virtually all of the human adult population is infected with EBV. Many EBV associated-tumors develop at increased frequencies in HIV infected individuals because the immune control of these malignancies is compromised by HIV co-infection. This interplay and the role of protective antibody responses against both pathogens will be explored in mice with reconstituted human immune system components (huNSG mice) via three aims.

Furthermore, huNSG mice will be instrumental in our fourth aim to determine the kinetics and distribution of HIV infection using radiolabeled HIV-specific antibodies and to investigate a series of antibody therapy-based approaches with the goal of developing novel therapeutic strategies for the elimination of HIV and EBV.

The proposed research project will test the following primary hypotheses:

1. HIV infection in EBV co-infected animals influences the development of EBV-associated tumo
2. Improvement of ADCC activity of HIV- and EBV-specific antibodies and/or conjugation with radioisotopes or toxins results in efficient clearance and elimination of HIV and EBV.
3. Combination antibody therapies including HIV specific and anti-PD-1 antibodies are more effective as compared to HIV-specific antibodies alone for the elimination of HIV.
4. Antibody radiolabeling  studies  with  microPet  imaging  will  allow  us  to  evaluate  the effectiveness of HIV different therapeutic strategies for the elimination of viral reservoirs