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.

Neutrophil extracellular traps (NETs) exacerbate severity of infant sepsis

“…However, it is important to point out that there is no clear consensus in the literature on the physiological equivalence by age between mice and humans. To mitigate this limitation, we performed a translational approach based on 2-week-old mice, which show similar patterns of immune responses to pediatric patients with a mean age of 3.5 years [56, 69, 70]. We observed that both mice and pediatric patients had an increase in the production of NETs during sepsis.…”

Response Type and Host Species may be Sufficient to Predict Dose-Response Curve Shape for Adenoviral Vector Vaccines

“…The systematic review identified 2787 references, reduced to 581 by title screening, then 300 by screening of the abstract. Screening by full text reduced the number of papers available for analysis to 35 [ 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 ]. These ranged across five Adenoviral species (B,C,D,E and G), six Host species (Cattle, Human, Monkey, Mouse, Rabbit and Rat), and two routes of administration (IM and SQ).…”

Paediatric sepsis survivors are resistant to sepsis‐induced long‐term immune dysfunction

“…To address this constraint, we took a translational approach. Specifically, we used 2‐ and 6‐week‐old mice because previous studies demonstrated that their immune responses are similar to those of paediatric and adult individuals (Heimesaat et al, 2016; Nazerai et al, 2016; Q. Zhang et al, 2013) and we recruited both paediatric and adult patients, with an average age of 4.69 years for the former and 53.43 years for the latter. We observed that both, sepsis‐surviving mice and adult patients, expanded Tregs and up‐regulated IL‐33 production in contrast to 2‐week‐old mice and the paediatric cohort.…”

“…To address this constraint, we took a translational approach. Specifically, we used 2-and 6-week-old mice because previous studies demonstrated that their immune responses are similar to those of paediatric and adult individuals (Heimesaat et al, 2016;Nazerai et al, 2016;Q. Zhang et al, 2013)…”