Early life vaccination: Generation of adult-quality memory CD8+ T cells in infant mice using non-replicating adenoviral vectors

Loulieta Nazerai; Maria Rosaria Bassi; Ida Elin Maria Uddbäck; Peter Johannes Holst; Jan Pravsgaard Christensen; Allan Randrup Thomsen

doi:10.1038/srep38666

Early life vaccination: Generation of adult-quality memory CD8⁺ T cells in infant mice using non-replicating adenoviral vectors

Loulieta Nazerai, Maria Rosaria Bassi, Ida Elin Maria Uddbäck, Peter Johannes Holst, Jan Pravsgaard Christensen, Allan Randrup Thomsen

5 Citations (Scopus)

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Abstract

Intracellular pathogens represent a serious threat during early life. Importantly, even though the immune system of newborns may be characterized as developmentally immature, with a propensity to develop Th2 immunity, significant CD8+ T-cell responses may still be elicited in the context of optimal priming. Replication deficient adenoviral vectors have been demonstrated to induce potent CD8+ T-cell response in mice, primates and humans. The aim of the present study was therefore to assess whether replication-deficient adenovectors could overcome the risk of overwhelming antigen stimulation during the first period of life and provide a pertinent alternative in infant vaccinology. To address this, infant mice were vaccinated with three different adenoviral vectors and the CD8+ T-cell response after early life vaccination was explored. We assessed the frequency, polyfunctionality and in vivo cytotoxicity of the elicited memory CD8+ T cells, as well as the potential of these cells to respond to secondary infections and confer protection. We further tested the impact of maternal immunity against our replication-deficient adenoviral vector during early life vaccination. Overall, our results indicate that memory CD8+ T cells induced by adenoviral vectors in infant mice are of good quality and match those elicited in the adult host.

Original language	English
Article number	38666
Journal	Scientific Reports
Volume	6
Number of pages	17
ISSN	2045-2322
DOIs	https://doi.org/10.1038/srep38666
Publication status	Published - 8 Dec 2016

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Early life vaccination: Generation of adult-quality memory CD8+ T cells in infant mice using non-replicating adenoviral vectorsFinal published version, 2.19 MBLicence: CC BY

Cite this

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title = "Early life vaccination: Generation of adult-quality memory CD8+ T cells in infant mice using non-replicating adenoviral vectors",

abstract = "Intracellular pathogens represent a serious threat during early life. Importantly, even though the immune system of newborns may be characterized as developmentally immature, with a propensity to develop Th2 immunity, significant CD8+ T-cell responses may still be elicited in the context of optimal priming. Replication deficient adenoviral vectors have been demonstrated to induce potent CD8+ T-cell response in mice, primates and humans. The aim of the present study was therefore to assess whether replication-deficient adenovectors could overcome the risk of overwhelming antigen stimulation during the first period of life and provide a pertinent alternative in infant vaccinology. To address this, infant mice were vaccinated with three different adenoviral vectors and the CD8+ T-cell response after early life vaccination was explored. We assessed the frequency, polyfunctionality and in vivo cytotoxicity of the elicited memory CD8+ T cells, as well as the potential of these cells to respond to secondary infections and confer protection. We further tested the impact of maternal immunity against our replication-deficient adenoviral vector during early life vaccination. Overall, our results indicate that memory CD8+ T cells induced by adenoviral vectors in infant mice are of good quality and match those elicited in the adult host.",

author = "Loulieta Nazerai and Bassi, {Maria Rosaria} and Uddb{\"a}ck, {Ida Elin Maria} and Holst, {Peter Johannes} and Christensen, {Jan Pravsgaard} and Thomsen, {Allan Randrup}",

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T2 - Generation of adult-quality memory CD8+ T cells in infant mice using non-replicating adenoviral vectors

AU - Nazerai, Loulieta

AU - Bassi, Maria Rosaria

AU - Uddbäck, Ida Elin Maria

AU - Holst, Peter Johannes

AU - Christensen, Jan Pravsgaard

AU - Thomsen, Allan Randrup

PY - 2016/12/8

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N2 - Intracellular pathogens represent a serious threat during early life. Importantly, even though the immune system of newborns may be characterized as developmentally immature, with a propensity to develop Th2 immunity, significant CD8+ T-cell responses may still be elicited in the context of optimal priming. Replication deficient adenoviral vectors have been demonstrated to induce potent CD8+ T-cell response in mice, primates and humans. The aim of the present study was therefore to assess whether replication-deficient adenovectors could overcome the risk of overwhelming antigen stimulation during the first period of life and provide a pertinent alternative in infant vaccinology. To address this, infant mice were vaccinated with three different adenoviral vectors and the CD8+ T-cell response after early life vaccination was explored. We assessed the frequency, polyfunctionality and in vivo cytotoxicity of the elicited memory CD8+ T cells, as well as the potential of these cells to respond to secondary infections and confer protection. We further tested the impact of maternal immunity against our replication-deficient adenoviral vector during early life vaccination. Overall, our results indicate that memory CD8+ T cells induced by adenoviral vectors in infant mice are of good quality and match those elicited in the adult host.

AB - Intracellular pathogens represent a serious threat during early life. Importantly, even though the immune system of newborns may be characterized as developmentally immature, with a propensity to develop Th2 immunity, significant CD8+ T-cell responses may still be elicited in the context of optimal priming. Replication deficient adenoviral vectors have been demonstrated to induce potent CD8+ T-cell response in mice, primates and humans. The aim of the present study was therefore to assess whether replication-deficient adenovectors could overcome the risk of overwhelming antigen stimulation during the first period of life and provide a pertinent alternative in infant vaccinology. To address this, infant mice were vaccinated with three different adenoviral vectors and the CD8+ T-cell response after early life vaccination was explored. We assessed the frequency, polyfunctionality and in vivo cytotoxicity of the elicited memory CD8+ T cells, as well as the potential of these cells to respond to secondary infections and confer protection. We further tested the impact of maternal immunity against our replication-deficient adenoviral vector during early life vaccination. Overall, our results indicate that memory CD8+ T cells induced by adenoviral vectors in infant mice are of good quality and match those elicited in the adult host.

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