Genetic Subtypes, Humoral Immunity, and Human Immunodeficiency Virus Type 1 Vaccine Development

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Abstract
Successful vaccination programs, particularly against influ- enza 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 vi- rus 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 geograph- ical area where a vaccine candidate is to be tested? The an- swers lie, at least in part, in a consideration of the humoral response to HIV-1 and, in particular, in the relationships be- tween the HIV-1 genetic subtypes and antigenic and neutral- ization 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 mislead- ing, or sometimes artifactual, results. Broadly similar issues are raised when considering the relationship between cellular im- mune 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 (9, 30, 39, 79). 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 im- munity to HIV-1 (15).

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