Peptide vaccines have been shown effective in preventing animal infection in some instances, and various formulations are under evaluation for their potential clinical use in humans. In the case of the Human Immunodeficiency Virus type-1 (HIV-1) infection, viral escape from immune surveillance restricts relevant neutralizing humoral responses to a handful of sites of vulnerability on the envelope glycoprotein. The membrane-proximal external region (MPER) on the gp41 transmembrane subunit has been identified as the only linear B-epitope that embodies an HIV vulnerability site. Thus, focusing humoral responses to MPER by peptide-based immunogens is a pursued goal in HIV vaccine development. The location of this sequence in the vicinity of the membrane interface, its composition (rich in aromatic residues), and the requirement of long-hydrophobic heavy-chain third complementarity-determining region loops for antibody-mediated neutralization suggests that in addition to the specific amino acid composition, antigenicity and immunogenicity of MPER can be modulated by membrane lipids. In this chapter, we give an overview of applications of lipid vesicles (liposomes) to the development of MPER-targeting vaccines, both as type-B adjuvants and epitope structure-shaping devices.
Among the rapidly growing arsenal of anti-cancer preventive and therapeutic options, vaccination is the one showing great promise. With the successful application of the three FDA-approved vaccines for HPV, HBV and metastatic prostate cancer and ongoing clinical trials for others, the quest is now to understand whether and how vaccination can help late stage cancer patients. Results of a recent work carried out in Norway has managed to successfully shed light on both fronts.
In this study, the unique immune response of a stage IV lung cancer patient who had gone into complete remission after having received just one single injection of a peptide vaccine was analyzed. This vaccine (GV1001), which is a 16-mer peptide matching the cancer cell-specific hTERT telomerase, elicited a very broad immune response in T helper cells of the patient. An in-depth immunological analysis of patient's peripheral blood mononuclear cells showed extensive intramolecular epitope spreading in CD4+ T (helper) cells. In addition, CD8+ T (cytotoxic) cells were also found to have recognized novel epitopes embedded within GV1001. Using a library of overlapping hTERT peptides, this team of researchers could further identify unique, reactive epitopes other than the vaccination peptide. These findings not only offer hope to advanced cancer patients, but also can offer insights for the design of future vaccines where manipulation of more than one cell type and incorporation of multiple epitopes would elicit a more efficient response towards eradicating tumor cells.
