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

Rebecca H Chisholm; Nikki Sonenberg; Jake A Lacey; Malcolm I McDonald; Manisha Pandey; Mark R Davies; Steven Y C Tong; Jodie McVernon; Nicholas Geard

doi:10.1371/journal.pcbi.1007182

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

PLoS Comput Biol. 2020 Jun 5;16(6):e1007182. doi: 10.1371/journal.pcbi.1007182. eCollection 2020 Jun.

Authors

Rebecca H Chisholm^{1

2}, Nikki Sonenberg², Jake A Lacey³, Malcolm I McDonald⁴, Manisha Pandey⁵, Mark R Davies⁶, Steven Y C Tong^{3

7

8}, Jodie McVernon⁹, Nicholas Geard^{9

10}

Affiliations

¹ Department of Mathematics and Statistics, La Trobe University, Melbourne, Victoria, Australia.
² Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia.
³ Doherty Department University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Victoria, Australia.
⁴ Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Queensland, Australia.
⁵ Institute for Glycomics, Gold Coast Campus, Griffith University, Brisbane, Queensland, Australia.
⁶ Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
⁷ Victorian Infectious Diseases Service, The Royal Melbourne Hospital, at the Peter Doherty Institute for Infection and Immunity, Victoria, Australia.
⁸ Menzies School of Health Research, Charles Darwin University, Darwin, Australia.
⁹ Victorian Infectious Diseases Reference Laboratory Epidemiology Unit at the Peter Doherty Institute for Infection and Immunity, The University of Melbourne and Royal Melbourne Hospital, Victoria, Australia.
¹⁰ School of Computing and Information Systems, Melbourne School of Engineering, The University of Melbourne, Melbourne, Victoria, Australia.

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Australia / epidemiology
Australia / ethnology
Basic Reproduction Number
Disease Models, Animal
Humans
Mice
Models, Theoretical
Population Dynamics
Population Groups
Skin Diseases / epidemiology*
Skin Diseases / immunology
Skin Diseases / microbiology
Skin Diseases / prevention & control
Streptococcal Infections / epidemiology*
Streptococcal Infections / immunology
Streptococcal Infections / prevention & control
Streptococcal Vaccines
Streptococcus pyogenes*

Substances

Streptococcal Vaccines

Grants and 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.