ORCID Profile
0000-0002-3770-3047
Current Organisations
VU Amsterdam
,
KU Leuven
,
Washington State University
,
Københavns Universitet Sundhedsvidenskabelige Fakultet
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Publisher: Springer Science and Business Media LLC
Date: 26-05-2022
DOI: 10.1038/S41590-022-01208-Z
Abstract: The ability of immune-modulating biologics to prevent and reverse pathology has transformed recent clinical practice. Full utility in the neuroinflammation space, however, requires identification of both effective targets for local immune modulation and a delivery system capable of crossing the blood–brain barrier. The recent identification and characterization of a small population of regulatory T (T reg ) cells resident in the brain presents one such potential therapeutic target. Here, we identified brain interleukin 2 (IL-2) levels as a limiting factor for brain-resident T reg cells. We developed a gene-delivery approach for astrocytes, with a small-molecule on-switch to allow temporal control, and enhanced production in reactive astrocytes to spatially direct delivery to inflammatory sites. Mice with brain-specific IL-2 delivery were protected in traumatic brain injury, stroke and multiple sclerosis models, without impacting the peripheral immune system. These results validate brain-specific IL-2 gene delivery as effective protection against neuroinflammation, and provide a versatile platform for delivery of erse biologics to neuroinflammatory patients.
Publisher: MDPI AG
Date: 27-05-2014
Publisher: MDPI AG
Date: 06-12-2021
DOI: 10.3390/V13122450
Abstract: Equine infectious anemia virus (EIAV) is a lentivirus similar to HIV that infects horses. Clinical and experimental studies demonstrating immune control of EIAV infection hold promise for efforts to produce an HIV vaccine. Antibody infusions have been shown to block both wild-type and mutant virus infection, but the mutant sometimes escapes. Using these data, we develop a mathematical model that describes the interactions between antibodies and both wild-type and mutant virus populations, in the context of continual virus mutation. The aim of this work is to determine whether repeated vaccinations through antibody infusions can reduce both the wild-type and mutant strains of the virus below one viral particle, and if so, to examine the vaccination period and number of infusions that ensure eradication. The antibody infusions are modelled using impulsive differential equations, a technique that offers insight into repeated vaccination by approximating the time-to-peak by an instantaneous change. We use impulsive theory to determine the maximal vaccination intervals that would be required to reduce the wild-type and mutant virus levels below one particle per horse. We show that seven boosts of the antibody vaccine are sufficient to eradicate both the wild-type and the mutant strains. In the case of a mutant virus infection that is given infusions of antibodies targeting wild-type virus (i.e., simulation of a heterologous infection), seven infusions were likewise sufficient to eradicate infection, based upon the data set. However, if the period between infusions was sufficiently increased, both the wild-type and mutant virus would eventually persist in the form of a periodic orbit. These results suggest a route forward to design antibody-based vaccine strategies to control viruses subject to mutant escape.
Publisher: Elsevier BV
Date: 04-2008
DOI: 10.1016/J.MBS.2008.02.001
Abstract: To stimulate the immune system's natural defenses, a post-infection HIV vaccination program to regularly boost cytotoxic T-lymphocytes has been proposed. We develop a mathematical model to describe such a vaccination program, where the strength of the vaccine and the vaccination intervals are constant. We apply the theory of impulsive differential equations to show that the model has an orbitally asymptotically stable periodic orbit, with the property of asymptotic phase. We show that, on this orbit, the vaccination frequency can be chosen so that the average number of infected CD4(+) T cells can be made arbitrarily low. We illustrate the results with numerical simulations and show that the model is robust with respect to both the parameter choices and the formulation of the model as a system of impulsive differential equations.
Publisher: MDPI AG
Date: 06-03-2023
DOI: 10.3390/V15030691
Abstract: Equine Infectious Anemia Virus (EIAV) is an important infection in equids, and its similarity to HIV creates hope for a potential vaccine. We analyze a within-host model of EIAV infection with antibody and cytotoxic T lymphocyte (CTL) responses. In this model, the stability of the biologically relevant endemic equilibrium, characterized by the coexistence of long-term antibody and CTL levels, relies upon a balance between CTL and antibody growth rates, which is needed to ensure persistent CTL levels. We determine the model parameter ranges at which CTL and antibody proliferation rates are simultaneously most influential in leading the system towards coexistence and can be used to derive a mathematical relationship between CTL and antibody production rates to explore the bifurcation curve that leads to coexistence. We employ Latin hypercube s ling and least squares to find the parameter ranges that equally ide the endemic and boundary equilibria. We then examine this relationship numerically via a local sensitivity analysis of the parameters. Our analysis is consistent with previous results showing that an intervention (such as a vaccine) intended to control a persistent viral infection with both immune responses should moderate the antibody response to allow for stimulation of the CTL response. Finally, we show that the CTL production rate can entirely determine the long-term outcome, regardless of the effect of other parameters, and we provide the conditions for this result in terms of the identified ranges for all model parameters.
Location: Denmark
No related grants have been discovered for Elissa Schwartz.