Current drug treatments in HIV focus on slowing or impeding the progress of the virus once it has infected the body's host cells. Recent approaches seek to develop therapies that prevent the virus from fusing with host cells. If the virus cannot fuse, it cannot enter inside the cell (infect) and reproduce, thereby facilitating the successful fight of the body's immune system against the invasion.
Meanwhile, HIV transmission generally occurs through sexual contacts. Indeed, semen and cervico-vaginal secretions may potentially transmit HIV to the gastrointestinal, anorectal and genitourinary tracts because they contain cell-free HIV particles and numerous HIV-infected cells. Contracting HIV infection may be subdivided into two main events. The first event, considered as a very early step, corresponds to viral translocation across mucosal surface that facilitates virus penetration and spreading into the body. The second event, which usually takes place after virus translocation such as by transcytosis, represents the infection step that leads to virus entry into target cells (ex. CD4+ T lymphocytes). Therefore, the HIV vaccine should ideally elicit immune responses not only in the blood but most importantly, also at the primary entry site, which corresponds to two important anatomically compartments: genital-reproductive tracts and intestine/rectal mucosal tissues. Therefore, vaccines or therapies for preventing this very early event of HIV translocation at the mucosa levels became another important research aspect.
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Figure 1. Mucosal antibody protection for preventing early HIV transmission
HIV may cross the mucosal barrier by different mechanisms such as transport by transcytosis (1), dendrites of dendritic cells or through M cells (2). Lesions caused to the mucosal tissue could also open the door to HIV entry (3). Having local mucosal IgA and IgG recognizing conserved areas of HIV gp41 protein might prevent the virus to cross the mucosal barrier, as well as blocking the infection of cells under the mucosa, which as probably the first target cells encountered by HIV. |
Until recently, vaccine development was focusing on clade B strains, which dominate the epidemic in industrialized countries but cause only about 12% of infections globally. Development of non-clade B candidates, having clade C as a key target became a priority and Mymetics seriously intends to invest all its research effort in developing its "universal" vaccine, with a primary interest for the clade C because of its world dominance, especially in countries under development like Africa, India and Asia. |
