In contrast to vaccination, whose aim is to prevent the establishment of productive infection by HIV, immunotherapy regimens using viral antigens are aimed at promoting or augmenting immune responses to HIV in patients who are already infected. The hypothesis for such approaches is that re-exposing the patient's immune system to antigen in a structured fashion may lead to the development of a more potent and directed immune response, which may reduce or eliminate the need for HAART in the infected individual. Design of therapeutic immunizations should likely have the same endpoint as HIV vaccines: expanding HIV-specific CTL. However, the methods used are likely to be different from those utilized in a vaccine. Patients receiving therapeutic immunizations are already HIV positive and thus are immunocompromised to some extent as a result of infection. Therefore, therapeutic immunizations will need to be designed in such a way as to account for the fact that CD4 cell help will be limited at best. The inclusion of adjuvants that promote CD8 cell responses that are more independent of CD4 T-cell help will be of great importance, as will the inclusion of adjuvants that promote better antigen-specific priming of CTL.
In the same vein as vaccines, immunotherapies have been studied using DNA, whole inactivated gp120-deleted virus and viral vectors [73–78]. Such therapies have shown promise both in animal models  as well as in human clinical trials [77,78]. Specifically, a study employing IL-2 in conjunction with a viral vector delivering SIV antigens showed that this type of immunization of SIVmac251 infected macaques substantially augmented SIV-specific CD8 T-cell responses . Additionally, therapeutic immunization of rhesus macaques with DNA encoding SIV antigens after infection with SIVmac251 resulted in considerably increased cellular immune responses along with long lasting reduction in viral loads after the animals were released from HAART . In regards to augmenting the responses generated by therapeutic immunization, specific cytokines seem to have great potential, especially IL-15 and IL-21. Both cytokines have been shown to induce increases in perforin and granzyme B levels in CD8 cells cultured ex vivo, giving CTL greater cytotoxic potential [71,81]. Moreover, peripheral blood mononuclear cells isolated from HIV positive patients have shown higher increases in granularity in response to IL-15 and IL-21 treatment than those taken from healthy individuals . Additionally, including IL-15 as an adjuvant in therapeutic immunization may help in the induction of antiviral CD8 cell activity by antigen presenting cells. CD8 T cells from HIV infected subjects co-cultured with mature dendritic cells restored the ability of the CD8 cells to inhibit viral replication by a non-cytotoxic mechanism . This effect was associated with the production of IL-15 by the dendritic cells . Such a result suggests that therapeutic immunization of HIV positive patients with antigen co-administered with IL-15 could also promote the stimulation of better CD8 cell anti-HIV responses. This effect is on top of the afore mentioned fact that IL-15 can induce the generation of CD8 cells that function somewhat independently of CD4 cell help .
Increased use of adjuvants in both vaccines and therapeutic immunizations for HIV infection should bring renewed vigor in attempts to induce lasting, robust immune responses against the virus. These adjuvants would boost HIV-specific immunity, modulate immune phenotype, and their use gives the scientific community a greater measure of control over what types of immune responses are driven in response to HIV antigen. Specific adjuvants including IL-12, IL-15 as well specific chemokines can strongly polarize the adaptive immune response towards a desired Th subtype. These look particularly important for clinical evaluation. Some adjuvants elicit strong responses from the innate immune system as well, such as IL-8 , and should be further studied in primate systems. This is an additional benefit of specific adjuvants, the induction of both the adaptive and innate arms of the immune system in response to HIV. While at this time there appears to be no single cytokine that is superior to others for use in vaccination and immune therapy, adjuvants such as IL-12 and IL-15 and specific chemokines such as Mip1α show promise in prophylactic vaccination approaches while IL-15 and IL-21 may prove beneficial for use in immune therapy for HIV infection.
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