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Epidemiological consequences of enduring strain_specific immunity.pdf (1.98 MB)

Epidemiological consequences of enduring strain-specific immunity requiring repeated episodes of infection

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posted on 19.03.2021, 05:49 by Rebecca Chisholm, N Sonenberg, JA Lacey, MI McDonald, M Pandey, MR Davies, SYC Tong, J McVernon, N Geard
© 2020 Chisholm et al. Group A Streptococcus (GAS) skin infections are caused by a diverse array of strain types and are highly prevalent in disadvantaged populations. The role of strain-specific immunity in preventing GAS infections is poorly understood, representing a critical knowledge gap in vaccine development. A recent GAS murine challenge study showed evidence that sterilising strain-specific and enduring immunity required two skin infections by the same GAS strain within three weeks. This mechanism of developing enduring immunity may be a significant impediment to the accumulation of immunity in populations. We used an agent-based mathematical model of GAS transmission to investigate the epidemiological consequences of enduring strain-specific immunity developing only after two infections with the same strain within a specified interval. Accounting for uncertainty when correlating murine timeframes to humans, we varied this maximum inter-infection interval from 3 to 420 weeks to assess its impact on prevalence and strain diversity, and considered additional scenarios where no maximum inter-infection interval was specified. Model outputs were compared with longitudinal GAS surveillance observations from northern Australia, a region with endemic infection. We also assessed the likely impact of a targeted strain-specific multivalent vaccine in this context. Our model produced patterns of transmission consistent with observations when the maximum inter-infection interval for developing enduring immunity was 19 weeks. Our vaccine analysis suggests that the leading multivalent GAS vaccine may have limited impact on the prevalence of GAS in populations in northern Australia if strain-specific immunity requires repeated episodes of infection. Our results suggest that observed GAS epidemiology from disease endemic settings is consistent with enduring strain-specific immunity being dependent on repeated infections with the same strain, and provide additional motivation for relevant human studies to confirm the human immune response to GAS skin infection.

Funding

This work was supported in part by a University of Melbourne Early Career Researcher Grant to RHC, NHMRC project grants (APP1098319 and APP1130455), and NHMRC Centre of Research Excellence (APP1058804). SYCT is supported by an NHMRC Career Development Fellowship (CDF1145033). JM is supported by an NHMRC Principal Research Fellowship (PRF1117140). MRD is supported by a University of Melbourne C.R. Roper Fellowship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

History

Publication Date

01/01/2020

Journal

PLoS Computational Biology

Volume

16

Issue

6

Article Number

e1007182

Pagination

22p. (p. 1-22)

Publisher

Public Library of Science

ISSN

1553-7358

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The Author reserves all moral rights over the deposited text and must be credited if any re-use occurs. Documents deposited in OPAL are the Open Access versions of outputs published elsewhere. Changes resulting from the publishing process may therefore not be reflected in this document. The final published version may be obtained via the publisher’s DOI. Please note that additional copyright and access restrictions may apply to the published version.

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