Towards Predicting Protective Vaccine Responses in the Very Young

Kollmann, Tobias R.; Marchant, Arnaud

doi:10.1016/j.it.2016.05.005

Cited by 13 publications

(6 citation statements)

References 71 publications

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“…The cytokine response in the sera was defined by the age of the animals. Infancy has been described as a period of relative immunodeficiency, but it is probably more accurate to describe it as period of differential immunity, which has an important impact on vaccine responses . Our data support the idea that the neonatal response is different not deficient, with higher IL‐1 α , CRP, GM‐CSF, G‐CSF and MCP‐1 than other ages of mice.…”

Section: Discussionmentioning

confidence: 99%

Inflammatory responses to influenza vaccination at the extremes of age

et al. 2017

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Age affects the immune response to vaccination, with individuals at the extremes of age responding poorly. The initial inflammatory response to antigenic materials shapes the subsequent adaptive response and so understanding is required about the effect of age on the profile of acute inflammatory mediators. In this study we measured the local and systemic inflammatory response after influenza vaccination or infection in neonatal, young adult and aged mice. Mice were immunized intramuscularly with inactivated influenza vaccine with and without the adjuvant MF59 and then challenged with H1N1 influenza. Age was the major factor affecting the inflammatory profile after vaccination: neonatal mice had more interleukin-1α (IL-1α), C-reactive protein (CRP) and granulocyte-macrophage colony-stimulating factor (GMCSF), young adults more tumour necrosis factor-α (TNF), and elderly mice more interleukin-1 receptor antagonist (IL-1RA), IL-2RA and interferon-γ-induced protein 10 (IP10). Notably the addition of MF59 induced IL-5, granulocyte colony-stimulating factor (G-CSF), Keratinocyte Chemotractant (KC) and monocyte chemoattractant protein 1 (MCP1) in all ages of animals and levels of these cytokines correlated with antibody responses. Age also had an impact on the efficacy of vaccination: neonatal and young adult mice were protected against challenge, but aged mice were not. There were striking differences in the localization of the cytokine response depending on the route of exposure: vaccination led to a high serum response whereas intranasal infection led to a low serum response but a high lung response. In conclusion, we demonstrate that age affects the inflammatory response to both influenza vaccination and infection. These age-induced differences need to be considered when developing vaccination strategies for different age groups.

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Section: Discussionmentioning

confidence: 99%

Inflammatory responses to influenza vaccination at the extremes of age

et al. 2017

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“…Furthermore, engagement of type I IFN pathways is associated with T helper type 1 (Th1)–biased immune responses and less airway hyper-reactivity after RSV reinfection in mice 24 . Age-based differences in type I IFN production and pathways involving B-cell proliferation and maturation have been reported in very young humans 25 .…”

Section: Introductionmentioning

confidence: 99%

Type I Interferon Potentiates IgA Immunity to Respiratory Syncytial Virus Infection During Infancy

Hijano

Siefker

Shrestha

et al. 2018

Sci Rep

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Respiratory syncytial virus (RSV) infection is the most frequent cause of hospitalization in infants and young children worldwide. Although mucosal RSV vaccines can reduce RSV disease burden, little is known about mucosal immune response capabilities in children. Neonatal or adult mice were infected with RSV; a subset of neonatal mice received interferon alpha (IFN-α) (intranasal) prior to RSV infection. B cells, B cell activating factor (BAFF) and IgA were measured by flow cytometry. RSV specific IgA was measured in nasal washes. Nasal associated lymphoid tissue (NALT) and lungs were stained for BAFF and IgA. Herein, we show in a mouse model of RSV infection that IFN-α plays a dual role as an antiviral and immune modulator and age-related differences in IgA production upon RSV infection can be overcome by IFN-α administration. IFN-α administration before RSV infection in neonatal mice increased RSV-specific IgA production in the nasal mucosa and induced expression of the B-cell activating factor BAFF in NALT. These findings are important, as mucosal antibodies at the infection site, and not serum antibodies, have been shown to protect human adults from experimental RSV infection.

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“…Conversely, transcriptional profiling of young individuals vaccinated against influenza virus revealed greater baseline gene expression events within high responders (classified by HAI titers 28-days post-vaccination) than low responders [20] . Our study utilizes young (<9 weeks old) piglets that may not appropriately represent a ‘baseline’ immune state at the time of vaccination described in other studies that use mature adults as cohorts, especially given that postnatal immune responses, hormonal factors, leukocyte populations, and cytokine production can vary within young, developing humans and livestock [6] , [16] , [24] , [39] , [40] . In swine, pre-vaccination differences in transcriptional networks were observed within PBMCs prior to M. hyopneumoniae -vaccination collected from high and low antibody responders defined at 118-days post-vaccination [5] .…”

Section: Discussionmentioning

confidence: 99%