Immunogen sequence: the fourth tier of AIDS vaccine design.

While worldwide efforts to develop an effective HIV-1 vaccine are underway, the virus continues to spread, particularly in developing countries where the delivery of antiviral therapies presents formidable challenges. Vaccine research has largely focused on three general aspects: vectors, adjuvants, and immunization schedules. Our group favor the use of computational methods to design potential immunogens that capture the genetic and biological features of circulating viruses. These methods allow researchers to predict, in silico, the presence of potential glycosylation sites, humoral immune responses, and epitope coverage. This review shall compare three computational approaches for immunogen design: the consensus sequence, which has at each site the modal nucleotide or amino acid residue across a sequence alignment; the most recent common ancestor, the sequence estimated at the basal node of the clades seen in the HIV-1 phylogeny; and the center of tree method, which minimizes the evolutionary distance to all sequences in the data set.