Patterns of antigenic diversity and the mechanisms that maintain them

Abstract

Many of the remaining challenges in infectious disease control involve pathogens that fail to elicit long-lasting immunity in their hosts. Antigenic variation is a common reason for this failure and a contributor to the complexity of vaccine design. Diversifying selection by the host immune system is commonly, and often correctly, invoked to explain antigenic variability in pathogens. However, there is a wide variety of patterns of antigenic variation across space and time, and within and between hosts, and we do not yet understand the determinants of these different patterns. This review describes five such patterns, taking as examples two bacteria (Streptococcus pneumoniae and Neisseria meningitidis), two viruses (influenza A and HIV-1), as well as the pathogens (taken as a group) for which antigenic variation is negligible. Pathogen-specific explanations for these patterns of diversity are critically evaluated, and the patterns are compared against predictions of theoretical models for antigenic diversity. Major remaining challenges are highlighted, including the identification of key protective antigens in bacteria, the design of vaccines to combat antigenic variability for viruses and the development of more systematic explanations for patterns of antigenic variation.

Figure 1

Antigenic diversity, pattern 1: constant high level of standing between-host diversity consistent over space and time; little within-host diversity, exemplified by Streptococcus pneumoniae. (a) Schematic of this pattern. Triangles, individual hosts within populations (rectangles); circles, pathogens within a host; colours, antigenic variants. (b) Serogroup representation among invasive isolates of S. pneumoniae at Boston City Hospital over four decades; data from Babl et al. (2001).

Figure 2

Antigenic diversity, pattern 2: substantial between-host diversity, changing over time and by geographic region; little within-host diversity, exemplified by Neisseria meningitidis. (a) Schematic as in figure 1a. (b) Global serogroup distribution of N. meningitidis strains mainly responsible for invasive disease; adapted from Stephens (2007).

Figure 3

Antigenic diversity, pattern 3: little diversity within-host or within the host population at a given time point, but rapid change over time, exemplified by influenza A virus. (a) Schematic as in figure 1a. (b) Phylogeny of haemagluttinin variants present in New York state and globally 1997–2005; reprinted from figure 2 of Nelson et al. (2006). Colours here represent years and are not connected with (a).

Figure 4

Antigenic diversity, pattern 4: substantial within-host diversity over time; little diversity at any single time point, and ongoing positive selection; global population does not reflect this selection but is highly diverse, exemplified by HIV-1. (a) Schematic as in figure 1a. (b) Within- and between-host phylogenies; reprinted from Fig. 1 of Grenfell et al. (2004)

Figure 5

Antigenic diversity, pattern 4: antigenic homogeneity, within and between hosts, over time. Schematic representation as in figure1a.