Population coverage by HLA class-I restricted cytotoxic T-lymphocyte epitopes

Vaccination using cytotoxic T-lymphocyte (CTL) epitopes has become a widely used immunization strategy, especially because their structure makes them an attractive alternative to the delivery of whole proteins as immunogens. Nonetheless, their use is limited, in particular because of their specifici ty, being recognized only by cognate HLA alleles. The potential for immuniz ing a substantial portion of an ethnically diverse population using a modes t number of peptides has been aided by the identification of HLA supertypes . However, the derivation of epitopes is often guided by methods that do no t guarantee cross-reactivity, so we consider the feasibility of providing v accine coverage to a multi-ethnic population under different: assumptions. In particular, two large datasets are used to estimate the number of peptid es needed to provide greater than or equal to 90% group-specific coverage o f a multi-ethnic population, when specificity is assumed to be either to a single serologic or molecular type. These assumptions are evaluated utilizi ng a clinically important epitope repertoire derived from two human cytomeg alovirus proteins, and data on the in vitro memory response elicited by the se peptides is presented. In summary, our combined theoretical and empiric studies suggest that 90% coverage of some ethnic groups is attainable with 11 uniquely defined HLA-restricted CTL epitopes. The derivation of four or more additional CTL epitopes is needed to attain 90% coverage of Blacks or Asians, the minimally covered groups. Ninety percent coverage of all major ethnic groups in a multi-ethnic population appears feasible without relying on cross-reactivity, but may require two to three times more CTL epitopes than estimated for serologic data, homogenous populations, or HLA alleles g rouped as supertypes.