AAV vector has recently been used to deliver single chain Fv immunoadhesin (scFVI) versions of rhesus monkey antibodies with neutralizing activity against SIV. High, persisting levels of scFVI were achieved in 6 of 9 rhesus monkeys and these six exhibited a sterilizing barrier against SIV challenge. Three of the nine monkeys developed antibody responses to the scFVI that they received and these three were not protected against SIV challenge. Two different approaches will be compared for AAV vector delivery of the authentic IgG verison of these scFVIs. We will determine whether delivery of authentic IgG decreases the frequency with which anti-anti responses are observed. We will determine whether AAV vector can be used to deliver dimeric secretory IgA and whether secretory IgA provides a more effective barrier to SIV infection by the mucosal route. Finally, we will determine whether antibody-dependent cellular cytotoxicity is important for the protective effects of the IgG versions of 4L6 and 5L7. Results from these experiments in rhesus monkeys will inform and guide development of analogous vectors for the prevention of HIV-1 infection in humans.

Public Health Relevance

Successful strategies have not been devised for the elicitation of antibodies with potent broadly-neutralizing activity against field strains of HIV-1. Use of AAV vector to deliver predefined antibodies with potent, broadly-neutralizing activity is a novel promising strategy for creating a sterilizing barrier to HIV-1 infection. Results from the proposed experiments in rhesus monkeys will uniform and guide development of such vectors for the prevention of HIV-1 infection in humans.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Program--Cooperative Agreements (U19)
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Special Emphasis Panel (ZAI1-LR-A)
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Beth Israel Deaconess Medical Center
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Okoye, Afam A; Hansen, Scott G; Vaidya, Mukta et al. (2018) Early antiretroviral therapy limits SIV reservoir establishment to delay or prevent post-treatment viral rebound. Nat Med 24:1430-1440
Abbink, Peter; Larocca, Rafael A; Dejnirattisai, Wanwisa et al. (2018) Therapeutic and protective efficacy of a dengue antibody against Zika infection in rhesus monkeys. Nat Med 24:721-723
Walters, Lucy C; Harlos, Karl; Brackenridge, Simon et al. (2018) Pathogen-derived HLA-E bound epitopes reveal broad primary anchor pocket tolerability and conformationally malleable peptide binding. Nat Commun 9:3137
Aid, Malika; Abbink, Peter; Larocca, Rafael A et al. (2017) Zika Virus Persistence in the Central Nervous System and Lymph Nodes of Rhesus Monkeys. Cell 169:610-620.e14
Abbink, Peter; Larocca, Rafael A; Visitsunthorn, Kittipos et al. (2017) Durability and correlates of vaccine protection against Zika virus in rhesus monkeys. Sci Transl Med 9:
Keele, Brandon F; Li, Wenjun; Borducchi, Erica N et al. (2017) Adenovirus prime, Env protein boost vaccine protects against neutralization-resistant SIVsmE660 variants in rhesus monkeys. Nat Commun 8:15740
Barouch, Dan H; Thomas, Stephen J; Michael, Nelson L (2017) Prospects for a Zika Virus Vaccine. Immunity 46:176-182
Ackerman, Margaret E; Barouch, Dan H; Alter, Galit (2017) Systems serology for evaluation of HIV vaccine trials. Immunol Rev 275:262-270
McMichael, Andrew J; Picker, Louis J (2017) Unusual antigen presentation offers new insight into HIV vaccine design. Curr Opin Immunol 46:75-81
Tomalka, Jeffrey; Ghneim, Khader; Bhattacharyya, Sanghamitra et al. (2016) The sooner the better: innate immunity as a path toward the HIV cure. Curr Opin Virol 19:85-91

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