Current status and perspectives of plant-based candidate vaccines against the human immunodeficiency virus (HIV).

Genetically engineered plants are economical platforms for the large-scale production of recombinant proteins and have been used over the last 21 years as models for oral vaccines against a wide variety of human infectious and autoimmune diseases with promising results. The main inherent advantages of this approach consist in the absence of purification needs and easy production and administration. One relevant infectious agent is the human immunodeficiency virus (HIV), since AIDS evolved as an alarming public health problem implicating very high costs for government agencies in most African and developing countries. The design of an effective and inexpensive vaccine able to limit viral spread and neutralizing the viral entry is urgently needed. Due to the limited efficacy of the vaccines assessed in clinical trials, new HIV vaccines able to generate broad immune profiles are a priority in the field. This review discusses the current advances on the topic of using plants as alternative expression systems to produce functional vaccine components against HIV, including antigens from Env, Gag and early proteins such as Tat and Nef. Ongoing projects of our group based on the expression of chimeric proteins comprising C4 and V3 domains from gp120, as an approach to elicit broadly neutralizing antibodies are mentioned. The perspectives of the revised approaches, such as the great need of assessing the oral immunogenicity and a detailed immunological characterization of the elicited immune responses, are also discussed.

HIV-1 infection and HIV-1 Tat protein permit the survival and replication of a non-pathogenic trypanosomatid in macrophages through TGF-beta1 production.

Monoxenic trypanosomatids, which usually are non-pathogenic in humans, have been detected in AIDS patients, but the mechanisms underlying the establishment of these protozoa in HIV-1-infected individuals are poorly understood. Here we addressed the role of HIV-1 and the HIV-1 Tat protein in the replication of the monoxenic trypanosomatid Blastocrithidia culicis in HIV-1-infected primary human macrophages. We found that HIV-1 and B. culicis replication augmented almost three times in co-infected macrophages, and that Tat antiserum significantly reduced the exacerbated protozoan growth. Exposure of B. culicis only infected macrophages to Tat protein also resulted in enhanced protozoan proliferation, reaching a twofold increase at 100 ng/mL. Electron microscopy analysis revealed that B. culicis and HIV-1 co-habit the same cells, and showed protozoan dividing forms inside macrophages. Protozoan replication diminished when B. culicis only infected macrophages were treated with Tat protein in the presence of anti-TGF-beta1 antibodies, suggesting a participation of this cytokine in the augmentation of protozoan multiplication. In fact, exogenous TGF-beta1 promoted the trypanosomatid replication in macrophages. Overall, our results suggest that HIV-1 infection deactivates the macrophage microbicidal activity, permitting the survival and multiplication of an otherwise non-pathogenic protozoan in these cells, a process partially mediated by Tat protein, via TGF-beta1 secretion.