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Antigenic diversity, transmission mechanisms, and the evolution of pathogens.

ABSTRACT: Pathogens have evolved diverse strategies to maximize their transmission fitness. Here we investigate these strategies for directly transmitted pathogens using mathematical models of disease pathogenesis and transmission, modeling fitness as a function of within- and between-host pathogen dynamics. The within-host model includes realistic constraints on pathogen replication via resource depletion and cross-immunity between pathogen strains. We find three distinct types of infection emerge as maxima in the fitness landscape, each characterized by particular within-host dynamics, host population contact network structure, and transmission mode. These three infection types are associated with distinct non-overlapping ranges of levels of antigenic diversity, and well-defined patterns of within-host dynamics and between-host transmissibility. Fitness, quantified by the basic reproduction number, also falls within distinct ranges for each infection type. Every type is optimal for certain contact structures over a range of contact rates. Sexually transmitted infections and childhood diseases are identified as exemplar types for low and high contact rates, respectively. This work generates a plausible mechanistic hypothesis for the observed tradeoff between pathogen transmissibility and antigenic diversity, and shows how different classes of pathogens arise evolutionarily as fitness optima for different contact network structures and host contact rates.

SUBMITTER: Lange A

PROVIDER: S-EPMC2759524 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature

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Antigenic diversity, transmission mechanisms, and the evolution of pathogens.

Lange Alexander A Ferguson Neil M NM

PLoS computational biology 20091016 10

Pathogens have evolved diverse strategies to maximize their transmission fitness. Here we investigate these strategies for directly transmitted pathogens using mathematical models of disease pathogenesis and transmission, modeling fitness as a function of within- and between-host pathogen dynamics. The within-host model includes realistic constraints on pathogen replication via resource depletion and cross-immunity between pathogen strains. We find three distinct types of infection emerge as max ...[more]

PMID: 19847288

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Project description:Avian A/H7 influenza viruses are a global threat to animal and human health. These viruses continue to cause outbreaks in poultry and have caused the highest number of reported zoonotic infections to date, highlighting their pandemic threat. Evidence for antigenic diversification of avian A/H7 influenza viruses exists; however, knowledge of the drivers and molecular basis of antigenic evolution of these viruses is limited. Here, antigenic cartography was used to analyze the global antigenic diversity of A/H7 influenza viruses and to determine the molecular basis of antigenic change in A/H7N9 viruses. A phylogenetic tree based on all available A/H7 HA sequences was generated, from which 52 representative, genetically diverse, antigens were selected for antigenic characterization using hemagglutination inhibition assays. The resulting data were used to compute an antigenic map using multidimensional scaling algorithms. High antigenic relatedness was observed between antigens and sera belonging to genetically divergent A/H7 (sub)lineages. The most striking antigenic change relative to the timespan of virus isolation was observed for the A/H7N9 viruses isolated between 2013 and 2019 in China. Amino acid changes at positions 116, 118, 125, 130, 151, and 217 in the hemagglutinin globular head were found to be the main determinants of antigenic evolution between A/H7N9 influenza virus prototypes. The A/H7 antigenic map and knowledge of the molecular determinants of their antigenic evolution will aid pandemic preparedness against A/H7 influenza viruses, specifically regarding the design of novel vaccines and vaccination strategies. IMPORTANCE A/H7 avian influenza viruses cause outbreaks in poultry globally, resulting in outbreaks with significant socio-economical impact and zoonotic risks. Occasionally, poultry vaccination programs have been implemented to reduce the burden of these viruses, which might result in an increased immune pressure accelerating antigenic evolution. In fact, evidence for antigenic diversification of A/H7 influenza viruses exists, posing challenges to pandemic preparedness and the design of vaccination strategies efficacious against drifted variants. Here, we performed a comprehensive analysis of the global antigenic diversity of A/H7 influenza viruses and identified the main substitutions in the hemagglutinin responsible for antigenic evolution in A/H7N9 viruses isolated between 2013 and 2019. The A/H7 antigenic map and knowledge of the molecular determinants of their antigenic evolution add value to A/H7 influenza virus surveillance programs, the design of vaccines and vaccination strategies, and pandemic preparedness.

Dataset Information

Antigenic diversity, transmission mechanisms, and the evolution of pathogens.

Publications

Antigenic diversity, transmission mechanisms, and the evolution of pathogens.

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