Successful vaccination programs, particularly against influenza virus infection, have provided us with an awareness of the need to immunize against the predominant circulating viral strains or genetic subtypes. The lessons and language derived from experience with influenza (and a few other) viruses have often been directly translated to human immunodeficiency virus type 1 (HIV-1) vaccine development. But how appropriate is this? Should an HIV-1 vaccine antigen always be based on the dominant genetic subtype that circulates in the geographical area where a vaccine candidate is to be tested? The answers lie, at least in part, in a consideration of the humoral response to HIV-1 and, in particular, in the relationships between the HIV-1 genetic subtypes and antigenic and neutralization serotypes. Here, we will review what is known about these relationships and seek to clarify confusion that has been created by the use of serological assays that generate misleading, or sometimes artifactual, results. Broadly similar issues are raised when considering the relationship between cellular immune responses and the HIV-1 genetic subtypes, but we will not discuss these here. Instead, we refer the reader to recent articles written by leading cellular immunologists . Significantly, a recent study on the cross-clade activity of cytotoxic T-lymphocyte responses in HIV-1-infected Ugandans argued that the use of nonendemic vaccine strains may be initially justified from the perspective of inducing cellular immunity to HIV-1.
