Models of RNA virus evolution and their roles in vaccine design

Ojosnegros, Samuel; Beerenwinkel, Niko

Vaccine design strategies based on whole viral protein sequences make extensive use of phylogenetics. In addition to the basic methods discussed above, HIV-specific probabilistic models of protein evolution have been constructed which allow for improved phylogenetic inference using likelihood or Bayesian methods [103] . The reconstructed phylogenetic tree can guide the selection of viral genomes to be included in the vaccine. Different selection strategies have been proposed to stimulate a broad immune response and to minimize the amount of sequence divergence between the antigen and contemporaneously circulating viruses. Natural strains that represent the total observed sequence space or derived consensus sequences have been selected as vaccine strains [104] [105] [106] . Probabilistic phylogenetic models also allow for inferring the DNA sequences at internal nodes of the tree which represent extinct common ancestors. The most recent common ancestor (MRCA) of a given set of viruses is the root of the phylogenetic tree for these sequences [107] . It has been proposed as a vaccine strain stimulating cross-reactive immune responses against all of its descendants [104, 108] . However, in asymmetric phylogenies, both the consensus sequence and the MRCA can perform poorly at minimizing the distance to contemporary strains [109] . To address this limitation, the center of tree node has been proposed. It is calculated as the node minimizing the least squares distance to all leaves of the phylogenetic tree [110] .