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Adaptive immune responses to vaccination reflect social status at first exposure in rhesus macaques

ABSTRACT: Social gradients are consistently associated with variation in health outcomes, including infectious disease. However, distinguishing between social gradients in antigen exposure versus susceptibility remains challenging. Here, we use a nonhuman primate model for chronic social stress to investigate how social status influences the influenza vaccine-induced adaptive immune response. We manipulated the social status of female rhesus macaques to test the response to influenza antigens in naïve individuals and after secondary exposure. Higher social status at the time of first exposure, but not at the time of secondary exposure, predicted stronger antibody responses to both exposures. Social status also drove gene expression differences for adaptive immune pathways, and genes that predict the magnitude of the antibody response overlap with those linked to social status. Thus, social gradients shape the adaptive immune response in a temporally dependent manner, with particular sensitivity at the time of initial antigen exposure.

ORGANISM(S): Macaca mulatta

PROVIDER: GSE318613 | GEO | 2026/02/06

REPOSITORIES: GEO

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Project description:Miao2010 - Innate and adaptive immune responses to primary Influenza A Virus infection This model is described in the article: Quantifying the early immune response and adaptive immune response kinetics in mice infected with influenza A virus. Miao H, Hollenbaugh JA, Zand MS, Holden-Wiltse J, Mosmann TR, Perelson AS, Wu H, Topham DJ. J. Virol. 2010 Jul; 84(13): 6687-6698 Abstract: Seasonal and pandemic influenza A virus (IAV) continues to be a public health threat. However, we lack a detailed and quantitative understanding of the immune response kinetics to IAV infection and which biological parameters most strongly influence infection outcomes. To address these issues, we use modeling approaches combined with experimental data to quantitatively investigate the innate and adaptive immune responses to primary IAV infection. Mathematical models were developed to describe the dynamic interactions between target (epithelial) cells, influenza virus, cytotoxic T lymphocytes (CTLs), and virus-specific IgG and IgM. IAV and immune kinetic parameters were estimated by fitting models to a large data set obtained from primary H3N2 IAV infection of 340 mice. Prior to a detectable virus-specific immune response (before day 5), the estimated half-life of infected epithelial cells is approximately 1.2 days, and the half-life of free infectious IAV is approximately 4 h. During the adaptive immune response (after day 5), the average half-life of infected epithelial cells is approximately 0.5 days, and the average half-life of free infectious virus is approximately 1.8 min. During the adaptive phase, model fitting confirms that CD8(+) CTLs are crucial for limiting infected cells, while virus-specific IgM regulates free IAV levels. This may imply that CD4 T cells and class-switched IgG antibodies are more relevant for generating IAV-specific memory and preventing future infection via a more rapid secondary immune response. Also, simulation studies were performed to understand the relative contributions of biological parameters to IAV clearance. This study provides a basis to better understand and predict influenza virus immunity. This model is hosted on BioModels Database and identified by: BIOMD0000000546. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

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Adaptive immune responses to vaccination reflect social status at first exposure in rhesus macaques

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