Phage display demonstrates durable differences in serological profile by route of inoculation in primary infections of non-human primates with Dengue Virus 1

Abstract Natural dengue virus (DENV) infections occur by mosquito bite but how the inoculation route affects the humoral immune response is unknown. We serologically profiled 20 non-human primates (NHP) from a prior study of DENV1 infection where animals were inoculated by mosquito (N = 10) or subcu...

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Autores principales:	Jayant V. Rajan, Michael McCracken, Caleigh Mandel-Brehm, Greg Gromowski, Simon Pollett, Richard Jarman, Joseph L. DeRisi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7a8a2bf739784470a54494e0dbf65fe5
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spelling	oai:doaj.org-article:7a8a2bf739784470a54494e0dbf65fe52021-12-02T14:49:18ZPhage display demonstrates durable differences in serological profile by route of inoculation in primary infections of non-human primates with Dengue Virus 110.1038/s41598-021-90318-z2045-2322https://doaj.org/article/7a8a2bf739784470a54494e0dbf65fe52021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-90318-zhttps://doaj.org/toc/2045-2322Abstract Natural dengue virus (DENV) infections occur by mosquito bite but how the inoculation route affects the humoral immune response is unknown. We serologically profiled 20 non-human primates (NHP) from a prior study of DENV1 infection where animals were inoculated by mosquito (N = 10) or subcutaneous injection (N = 10). Using a comprehensive, densely tiled and highly redundant pan-flavivirus programmable phage library containing 91,562 overlapping 62 amino acid peptides, we produced a high-resolution map of linear peptide sequences enriched during DENV seroconversion. Profiles in mosquito-inoculated and subcutaneously-inoculated animals were similar up to 90 days after primary infection, but diverged at 1 year with differences in sero-reactivity in the Envelope (E; residues 215–406; p < 0.08), and Nonstructural-3 (NS3; residues 549–615; p < 0.05) proteins in mosquito-inoculated versus subcutaneously-inoculated animals. Within the E protein, residues 339–384 in domain III accounted for > 99% of the observed sero-reactivity difference. Antibody breadth did not vary by mode of inoculation. The differential reactivity to E domain III seen by phage display validated orthogonally by ELISA, but did not correlate with late neutralization titers. Serological profiling of humoral immune responses to DENV infection in NHP by programmable phage display demonstrated durable differences in sero-reactivity by route of inoculation.Jayant V. RajanMichael McCrackenCaleigh Mandel-BrehmGreg GromowskiSimon PollettRichard JarmanJoseph L. DeRisiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jayant V. Rajan Michael McCracken Caleigh Mandel-Brehm Greg Gromowski Simon Pollett Richard Jarman Joseph L. DeRisi Phage display demonstrates durable differences in serological profile by route of inoculation in primary infections of non-human primates with Dengue Virus 1
description	Abstract Natural dengue virus (DENV) infections occur by mosquito bite but how the inoculation route affects the humoral immune response is unknown. We serologically profiled 20 non-human primates (NHP) from a prior study of DENV1 infection where animals were inoculated by mosquito (N = 10) or subcutaneous injection (N = 10). Using a comprehensive, densely tiled and highly redundant pan-flavivirus programmable phage library containing 91,562 overlapping 62 amino acid peptides, we produced a high-resolution map of linear peptide sequences enriched during DENV seroconversion. Profiles in mosquito-inoculated and subcutaneously-inoculated animals were similar up to 90 days after primary infection, but diverged at 1 year with differences in sero-reactivity in the Envelope (E; residues 215–406; p < 0.08), and Nonstructural-3 (NS3; residues 549–615; p < 0.05) proteins in mosquito-inoculated versus subcutaneously-inoculated animals. Within the E protein, residues 339–384 in domain III accounted for > 99% of the observed sero-reactivity difference. Antibody breadth did not vary by mode of inoculation. The differential reactivity to E domain III seen by phage display validated orthogonally by ELISA, but did not correlate with late neutralization titers. Serological profiling of humoral immune responses to DENV infection in NHP by programmable phage display demonstrated durable differences in sero-reactivity by route of inoculation.
format	article
author	Jayant V. Rajan Michael McCracken Caleigh Mandel-Brehm Greg Gromowski Simon Pollett Richard Jarman Joseph L. DeRisi
author_facet	Jayant V. Rajan Michael McCracken Caleigh Mandel-Brehm Greg Gromowski Simon Pollett Richard Jarman Joseph L. DeRisi
author_sort	Jayant V. Rajan
title	Phage display demonstrates durable differences in serological profile by route of inoculation in primary infections of non-human primates with Dengue Virus 1
title_short	Phage display demonstrates durable differences in serological profile by route of inoculation in primary infections of non-human primates with Dengue Virus 1
title_full	Phage display demonstrates durable differences in serological profile by route of inoculation in primary infections of non-human primates with Dengue Virus 1
title_fullStr	Phage display demonstrates durable differences in serological profile by route of inoculation in primary infections of non-human primates with Dengue Virus 1
title_full_unstemmed	Phage display demonstrates durable differences in serological profile by route of inoculation in primary infections of non-human primates with Dengue Virus 1
title_sort	phage display demonstrates durable differences in serological profile by route of inoculation in primary infections of non-human primates with dengue virus 1
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/7a8a2bf739784470a54494e0dbf65fe5
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Phage display demonstrates durable differences in serological profile by route of inoculation in primary infections of non-human primates with Dengue Virus 1

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