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What Controls the Acute Viral Infection Following Yellow Fever Vaccination?

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Abstract

Does target cell depletion, innate immunity, or adaptive immunity play the dominant role in controlling primary acute viral infections? Why do some individuals have higher peak virus titers than others? Answering these questions is a basic problem in immunology and can be particularly difficult in humans due to limited data, heterogeneity in responses in different individuals, and limited ability for experimental manipulation. We address these questions for infections following vaccination with the live attenuated yellow fever virus (YFV-17D) by analyzing viral load data from 80 volunteers. Using a mixed effects modeling approach, we find that target cell depletion models do not fit the data as well as innate or adaptive immunity models. Examination of the fits of the innate and adaptive immunity models to the data allows us to select a minimal model that gives improved fits by widely used model selection criteria (AICc and BIC) and explains why it is hard to distinguish between the innate and adaptive immunity models. We then ask why some individuals have over 1000-fold higher virus titers than others and find that most of the variation arises from differences in the initial/maximum growth rate of the virus in different individuals.

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Authors and Affiliations

  1. Department of Biology, Emory University, Atlanta, GA, USA

    James Moore, Hasan Ahmed, Jonathan Jia & Rustom Antia

  2. Department of Microbiology and Immunology, Emory University, Atlanta, GA, USA

    Rama Akondy

  3. Emory Vaccine Center, Emory University, Atlanta, GA, USA

    Rafi Ahmed

Authors
  1. James Moore
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  2. Hasan Ahmed
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  3. Jonathan Jia
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  4. Rama Akondy
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  5. Rafi Ahmed
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  6. Rustom Antia
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Corresponding author

Correspondence to James Moore.

Additional information

This work was supported by four NIH Grants NIH U54GM111274, NIH R01AI110720 (to R. Antia), NIH U19AI11789102 (to R.Antia and R.Ahmed), and U19AI057266 (to R. Ahmed).

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Moore, J., Ahmed, H., Jia, J. et al. What Controls the Acute Viral Infection Following Yellow Fever Vaccination?. Bull Math Biol 80, 46–63 (2018). https://doi.org/10.1007/s11538-017-0365-3

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  • DOI: https://doi.org/10.1007/s11538-017-0365-3

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