scholarly journals Multiscale Immune Selection and the Transmission-Diversity Feedback in Antigenically Diverse Pathogen Systems

2018 ◽  
Vol 192 (6) ◽  
pp. E189-E201 ◽  
Author(s):  
Thomas Holding ◽  
John Joseph Valletta ◽  
Mario Recker
Keyword(s):  
Immune Selection ◽  
Transmission Diversity

scholarly journals Multi-scale immune selection and the transmission-diversity feedback of Plasmodium falciparum malaria

2017 ◽  
Author(s):  
Thomas Holding ◽  
John Joseph Valletta ◽  
Mario Recker
Keyword(s):  
Plasmodium Falciparum ◽  
Disease Transmission ◽  
Antigenic Variation ◽  
Population Level ◽  
Plasmodium Falciparum Malaria ◽  
Malaria Prevalence ◽  
Feedback Mechanism ◽  
Immune Selection ◽  
Antigenic Diversity ◽  
Transmission Diversity

AbstractAntigenic diversity is a key factor underlying the complex epidemiology of Plasmodium falciparum malaria. Within-host clonal antigenic variation limits host exposure to the parasite’s antigenic repertoire, while the high degree of diversity at the population-level requires multiple exposures for hosts to acquire anti-disease immunity. This diversity is predominantly generated through mitotic and meiotic recombination between individual genes and multi-gene repertoires and is therefore expected to respond dynamically to changes in transmission and immune selection. We hypothesised that this coupling creates a positive feedback mechanism whereby infection and disease transmission promotes the generation of diversity, which itself facilitates immune evasion and hence further infection and transmission. To investigate the link between diversity and malaria prevalence in more detail we developed an individual-based model in which antigenic diversity emerges as a dynamic property from the underlying transmission processes. We show that the balance between stochastic extinction and the generation of new antigenic variants is intrinsically linked to within-host and between-host immune selection, which in turn determines the level of diversity that can be maintained in a given population. We further show that the transmission-diversity feedback can lead to temporal lags in the response to natural or intervention-induced perturbations in transmission rates. These results will add to our understanding of the epidemiological dynamics of P. falciparum malaria in different transmission settings and will have important implications for monitoring and assessing the effectiveness of disease control efforts.

scholarly journals An Antigenic Thrift-Based Approach to Influenza Vaccine Design

Vaccines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 657
Author(s):  
Jai S. Bolton ◽  
Hannah Klim ◽  
Judith Wellens ◽  
Matthew Edmans ◽  
Uri Obolski ◽  
...  
Keyword(s):  
Influenza Vaccine ◽  
Influenza Season ◽  
Vaccine Design ◽  
Antigenic Drift ◽  
Influenza Vaccines ◽  
Immune Protection ◽  
Immune Selection ◽  
Drift Theory ◽  
Gradual Accumulation ◽  
Additional Constraints

The antigenic drift theory states that influenza evolves via the gradual accumulation of mutations, decreasing a host’s immune protection against previous strains. Influenza vaccines are designed accordingly, under the premise of antigenic drift. However, a paradox exists at the centre of influenza research. If influenza evolved primarily through mutation in multiple epitopes, multiple influenza strains should co-circulate. Such a multitude of strains would render influenza vaccines quickly inefficacious. Instead, a single or limited number of strains dominate circulation each influenza season. Unless additional constraints are placed on the evolution of influenza, antigenic drift does not adequately explain these observations. Here, we explore the constraints placed on antigenic drift and a competing theory of influenza evolution – antigenic thrift. In contrast to antigenic drift, antigenic thrift states that immune selection targets epitopes of limited variability, which constrain the variability of the virus. We explain the implications of antigenic drift and antigenic thrift and explore their current and potential uses in the context of influenza vaccine design.

scholarly journals Exploiting knowledge of immune selection in HIV-1 to detect HIV-specific CD8 T-cell responses

Vaccine ◽  
2010 ◽  
Vol 28 (37) ◽  
pp. 6052-6057 ◽  
Author(s):  
Coral-Ann M. Almeida ◽  
Steven G. Roberts ◽  
Rebecca Laird ◽  
Elizabeth McKinnon ◽  
Imran Ahmad ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Immune Selection ◽  
Cell Responses ◽  
Hiv 1

scholarly journals Mutational escape from CD8+ T cell immunity

2005 ◽  
Vol 201 (11) ◽  
pp. 1709-1714 ◽  
Author(s):  
David G. Bowen ◽  
Christopher M. Walker
Keyword(s):  
Mhc Class I ◽  
T Lymphocyte ◽  
Selection Pressure ◽  
Cytotoxic T Lymphocyte ◽  
Viral Persistence ◽  
Cd8 T Cell ◽  
Viral Escape ◽  
Immune Selection ◽  
Cell Immunity

The mechanisms by which the hepatitis C virus (HCV) establishes persistence are not yet fully understood. Previous chimpanzee and now human studies suggest that mutations within MHC class I–restricted HCV epitopes might contribute to viral escape from cytotoxic T lymphocyte (CTL) responses. However, there are several outstanding questions regarding the role of escape mutations in viral persistence and their fate in the absence of immune selection pressure.

scholarly journals Scaling laws describe memories of host–pathogen riposte in the HIV population

2015 ◽  
Vol 112 (7) ◽  
pp. 1965-1970 ◽  
Author(s):  
John P. Barton ◽  
Mehran Kardar ◽  
Arup K. Chakraborty
Keyword(s):  
Neural Networks ◽  
Immune Responses ◽  
Scaling Laws ◽  
Mechanistic Model ◽  
Solvable Model ◽  
Effective Control ◽  
Immune Selection ◽  
Exactly Solvable ◽  
Host Pathogen ◽  
Human Immune

The enormous genetic diversity and mutability of HIV has prevented effective control of this virus by natural immune responses or vaccination. Evolution of the circulating HIV population has thus occurred in response to diverse, ultimately ineffective, immune selection pressures that randomly change from host to host. We show that the interplay between the diversity of human immune responses and the ways that HIV mutates to evade them results in distinct sets of sequences defined by similar collectively coupled mutations. Scaling laws that relate these sets of sequences resemble those observed in linguistics and other branches of inquiry, and dynamics reminiscent of neural networks are observed. Like neural networks that store memories of past stimulation, the circulating HIV population stores memories of host–pathogen combat won by the virus. We describe an exactly solvable model that captures the main qualitative features of the sets of sequences and a simple mechanistic model for the origin of the observed scaling laws. Our results define collective mutational pathways used by HIV to evade human immune responses, which could guide vaccine design.

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