Nanotechnology against HIV-1: safety and biodistribution of prophylactic microbicides and use as transfectants for a DC-based therapeutic vaccine
Author
Martín Moreno, AlbaAdvisor
Muñoz Fernández, María ÁngelesEntity
UAM. Departamento de Biología Molecular; Hospital General Universitario Gregorio MarañónDate
2020-02-14Subjects
Virus inmunodeficiencia humana (VIH) - Tratamiento - Tesis doctorales; Virus inmunodeficiencia humana (VIH) - Prevención - Mujeres - Tesis doctorales; Biología y Biomedicina / BiologíaNote
Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de lectura: 14-02-2020Esta tesis tiene embargado el acceso al texto completo hasta el 14-08-2021
Esta obra está bajo una licencia de Creative Commons Reconocimiento-NoComercial-SinObraDerivada 4.0 Internacional.
Abstract
Human Immunodeficiency Virus (HIV) has been a challenging riddle for the scientific community and the
health system since its discovery in 1984. According to UNAIDS data, almost 38 million people are
currently living with HIV worldwide and only 23.3 have access to antiretroviral therapy (ART). Far from
reaching the 2020 objectives, there is a prevention crisis, as the number of new infections decrease at a
disturbing low rate, despite all the prophylactic methods available. Microbicides are rising as promising
alternatives in response to the need of efficient, immediate and inconspicuous preventive methods,
especially of women in developing countries.
G2-S16 dendrimer is a microbicide designed for a topical application in the vagina and has been shown
to be efficient in the prevention of HIV-1 infection. It is currently on the way to clinical trials. In this
study, we test the safety of G2-S16 regarding its effect on the immune cells found in the female
reproductive tract. The results showed that G2-S16 dendrimer does not modify TLR expression in
epithelial cells, dendritic cells (DCs), macrophages (MΦs), or CD4+ T cells, nor does it affect their
differentiation or activation of DCs, MΦs, CD4+ and CD8+ T cells, or B cells. In vivo studies in mice
suggested that G2-S16 dendrimer is safe for vaginal and intravenous application, as it does not harm the
vaginal epithelium, hematocrit, or structure and function of the organs studied (brain, heart, kidney,
liver and spleen).
HIV transmission correlates with unintended pregnancies, highlighting the health and social benefits of a
gel of dual microbicide and contraceptive effect. We combined the contraceptive drug Platycodin D with
G2-S16 and the results demonstrate that both compounds keep their effect in combination.
Another scientific challenge in the fight against HIV is the finding of a functional cure. HIV is nowadays a
chronic infection thanks to antiretroviral therapy, but it has issues like the appearing resistances, or lack
of adhesion of the patients. A DC-based therapeutic vaccine would address these issues. We aimed to
design a vaccine, testing two nanocompounds to transfect DCs with a HIV-derived peptide, maturing DCs
in vitro, and studying their ability to stimulate a HIV-specific T and B cell immune response.
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