Mucosal AIDS Vaccines

Abstract

Debates are still being waged over what is the best strategy for developing a potent AIDS vaccine. All the obvious approaches to making AIDS vaccines have been tried in the past two decades without much success. It is clear that new thinking and a revision of prevailing dogmas needs to be in place if we really want a vaccine. Conventional envelope-based antibody-inducing vaccines do not appear to hold promise, and broadly-neutralizing antibodies are now being searched as an alternative to the failed approach with subunit vaccines. The current consensus is that cellular immune responses, especially those mediated by CD8 cytotoxic/suppressor (CTL) and CD4 helper T lymphocytes, are needed to control HIV. Vaccines capable of inducing cell-mediated responses are, therefore, considered critical for controlling the spread of HIV. DNA-based vaccines triggering CTL reaction are currently thought to be an answer, but will they fulfill the promise? In the following paragraphs, a critical assessment of the state of the art will be provided in an attempt to analyze what we know and still don't know. The focus of this review is primarily on mucosal vaccines-a relatively new area in AIDS research. The update on V-1 Immunitor, the first mucosal AIDS vaccine available commercially, is provided within this context. Some of the reviewed concepts may be disputable, but without departure from the uninspiring consensus no substantial progress in the AIDS vaccine field can be envisioned.

Production of a Short Recombinant C4V3 HIV-1 Immunogen That Induces Strong Anti-HIV Responses by Systemic and Mucosal Routes Without the Need of Adjuvants

“…Although few studies have demonstrated the induction of mucosal IgA after i.m. immunization (7,12,13), it is generally accepted that systemic immunization is not effective for the induction of mucosal immune responses (8).…”

Therapeutic AIDS Vaccines

“…These observations indicate that mucosal and/or systemic allo-or auto-immunization reduces HIV infection and this approach needs to be investigated further in preventive and therapeutic vaccinations for AIDS. This research combined with new developments in innate mucosal immunity in response to commensal pathogens points the direction for future studies [172].…”

AIDS Vaccines and Reproductive Immunology

“…The difference from other blood-derived vaccines in this category is that this particular vaccine is formulated as a pill to be taken orally, hence targeting mucosal immune response. AIDS patients treated with V1 displayed body weight gain, rise in T cell counts, decrease in viremia, serodeconversion, reduced incidence in opportunistic infections, and general clinical improvement [59][60][61][62][63][64][65][66][67]. V1-treated patients had also higher survival rate -a major clinical endpoint that has never been achieved in published therapeutic vaccine trials [68].…”

“…While most of the critiques have already been addressed in above cited publications [60,63] it is understandable that such an innovative approach is initially met with skepticism and it will take time to overcome the incredulity barrier.…”