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When does humoral memory enhance infection?

Antibodies and humoral memory are key components of the adaptive immune system. We consider and computationally model mechanisms by which humoral memory present at baseline might increase rather than decrease infection load; we refer to this effect as EI-HM (enhancement of infection by humoral memor...

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Autores principales: Nikas, Ariel, Ahmed, Hasan, Moore, Mia R., Zarnitsyna, Veronika I., Antia, Rustom
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10470880/
https://www.ncbi.nlm.nih.gov/pubmed/37603552
http://dx.doi.org/10.1371/journal.pcbi.1011377
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author Nikas, Ariel
Ahmed, Hasan
Moore, Mia R.
Zarnitsyna, Veronika I.
Antia, Rustom
author_facet Nikas, Ariel
Ahmed, Hasan
Moore, Mia R.
Zarnitsyna, Veronika I.
Antia, Rustom
author_sort Nikas, Ariel
collection PubMed
description Antibodies and humoral memory are key components of the adaptive immune system. We consider and computationally model mechanisms by which humoral memory present at baseline might increase rather than decrease infection load; we refer to this effect as EI-HM (enhancement of infection by humoral memory). We first consider antibody dependent enhancement (ADE) in which antibody enhances the growth of the pathogen, typically a virus, and typically at intermediate ‘Goldilocks’ levels of antibody. Our ADE model reproduces ADE in vitro and enhancement of infection in vivo from passive antibody transfer. But notably the simplest implementation of our ADE model never results in EI-HM. Adding complexity, by making the cross-reactive antibody much less neutralizing than the de novo generated antibody or by including a sufficiently strong non-antibody immune response, allows for ADE-mediated EI-HM. We next consider the possibility that cross-reactive memory causes EI-HM by crowding out a possibly superior de novo immune response. We show that, even without ADE, EI-HM can occur when the cross-reactive response is both less potent and ‘directly’ (i.e. independently of infection load) suppressive with regard to the de novo response. In this case adding a non-antibody immune response to our computational model greatly reduces or completely eliminates EI-HM, which suggests that ‘crowding out’ is unlikely to cause substantial EI-HM. Hence, our results provide examples in which simple models give qualitatively opposite results compared to models with plausible complexity. Our results may be helpful in interpreting and reconciling disparate experimental findings, especially from dengue, and for vaccination.
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spelling pubmed-104708802023-09-01 When does humoral memory enhance infection? Nikas, Ariel Ahmed, Hasan Moore, Mia R. Zarnitsyna, Veronika I. Antia, Rustom PLoS Comput Biol Research Article Antibodies and humoral memory are key components of the adaptive immune system. We consider and computationally model mechanisms by which humoral memory present at baseline might increase rather than decrease infection load; we refer to this effect as EI-HM (enhancement of infection by humoral memory). We first consider antibody dependent enhancement (ADE) in which antibody enhances the growth of the pathogen, typically a virus, and typically at intermediate ‘Goldilocks’ levels of antibody. Our ADE model reproduces ADE in vitro and enhancement of infection in vivo from passive antibody transfer. But notably the simplest implementation of our ADE model never results in EI-HM. Adding complexity, by making the cross-reactive antibody much less neutralizing than the de novo generated antibody or by including a sufficiently strong non-antibody immune response, allows for ADE-mediated EI-HM. We next consider the possibility that cross-reactive memory causes EI-HM by crowding out a possibly superior de novo immune response. We show that, even without ADE, EI-HM can occur when the cross-reactive response is both less potent and ‘directly’ (i.e. independently of infection load) suppressive with regard to the de novo response. In this case adding a non-antibody immune response to our computational model greatly reduces or completely eliminates EI-HM, which suggests that ‘crowding out’ is unlikely to cause substantial EI-HM. Hence, our results provide examples in which simple models give qualitatively opposite results compared to models with plausible complexity. Our results may be helpful in interpreting and reconciling disparate experimental findings, especially from dengue, and for vaccination. Public Library of Science 2023-08-21 /pmc/articles/PMC10470880/ /pubmed/37603552 http://dx.doi.org/10.1371/journal.pcbi.1011377 Text en © 2023 Nikas et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Nikas, Ariel
Ahmed, Hasan
Moore, Mia R.
Zarnitsyna, Veronika I.
Antia, Rustom
When does humoral memory enhance infection?
title When does humoral memory enhance infection?
title_full When does humoral memory enhance infection?
title_fullStr When does humoral memory enhance infection?
title_full_unstemmed When does humoral memory enhance infection?
title_short When does humoral memory enhance infection?
title_sort when does humoral memory enhance infection?
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10470880/
https://www.ncbi.nlm.nih.gov/pubmed/37603552
http://dx.doi.org/10.1371/journal.pcbi.1011377
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