Evaluation and strategies to generate mucosal antibodies against HIV-1 infection

• Main Author: Klein, Katja
• Published: St George's, University of London 2012
• Subjects: 616.979201
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.568768

Mucosal HIV infection is currently the leading cause of the global AIDS epidemic, with most infections occurring through sexual intercourse. A truly effective vaccine capable of protecting vaccines from HIV acquisition will likely require mucosal mediated immune protection. Previous non-human primate studies have provided the proof of concept that neutralising antibodies can prevent infection, however the levels of antibody at mucosal surfaces required for protection have not been fully characterised. Furthermore, to date no effective vaccination strategy has been shown to efficiently induce protective mucosal humoral responses. In spite of this, recent evidence suggests that directly targeting vaccines towards mucosal surfaces may enhance local immune responses. Thus this thesis has two hypotheses. First to determine the levels of mucosal antibody required to provide sterilising protection in the macaque model. Second using the murine model to develop strategies to enhance vaccine antigen delivery across mucosal surfaces, as an approach to induce mucosal humoral immune responses. We demonstrate that the presence of neutralising 2F5 IgG antibody at the time of vaginal challenge is able to give sterilising protection in the macaque model, and that the whole IgG molecule was essential for protection, while the Fab' portion was inefficient. Furthermore we show that permeation enhancer can play an important role in the delivery of vaccine antigens across mucosal surfaces, where the vaginal route of immunisation is the least effective one. In summary, we present supporting data for the role of humoral immune responses in protection against HIV infection and ways in which to increase the bioavailability of mucosally applied antigens to initiate the development of mucosal antibodies