| 1. |
- Bacchus, Philip, et al.
(författare)
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Civil-military collaboration to facilitate rapid deployment of a mobile laboratory in early response to covid-19 : A high-readiness exercise
- 2021
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Ingår i: HEALTH SECURITY. - : Mary Ann Liebert. - 2326-5094 .- 2326-5108. ; 19:5, s. 488-497
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Tidskriftsartikel (refereegranskat)abstract
- Rapid and adaptable diagnostic capabilities are of great importance in the face of emerging infectious diseases. In an outbreak, timely establishment of diagnostic routines is crucial to identifying cases and preventing the spread of the disease, especially when faced with high-consequence pathogens. In this article, we describe a multiagency exercise including the rapid deployment and diagnostic adaptation of the Swedish Armed Forces mobile laboratory (biological field analysis laboratory) in the context of COVID-19. This deployment was initiated as a high-readiness exercise at the end of January 2020, when the global development of the outbreak was still uncertain. Through collaboration with the Public Health Agency of Sweden and a civilian hospital, a real-time reverse transcriptase polymerase chain reaction method specific to SARS-CoV-2 was made available and adapted to the mobile laboratory, and the team established and evaluated a functional and efficient diagnostic asset along with a logistical support chain. We also organized and evaluated mobile testing teams, and the method was later used in large-scale, national, cross-sectional COVID-19 surveys in several regions of Sweden. In this article, we focus on the challenges of overbridging the civil-military interface in this context and identifying lessons learned and added values to the response during the early pandemic. We propose that the experiences from this exercise and governmental agency collaboration are valuable in preparation for future outbreaks.
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| 2. |
- Boberg, Andreas, et al.
(författare)
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Murine models for HIV vaccination and challenge
- 2008
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Ingår i: Expert Review of Vaccines. - : Informa UK Limited. - 1476-0584 .- 1744-8395. ; 7:1, s. 117-130
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Tidskriftsartikel (refereegranskat)abstract
- HIV-1 only infects humans and chimpanzees. SIV or SHIV are, therefore, used as models for HIV in rhesus, cynomologus and pigtail macaques. Since conducting experiments in primate models does not fully mimic infection or vaccination against HIV-1 and is expensive, there is a great need for small-animal models in which it is possible to study HIV-1 infection, immunity and vaccine efficacy. This review summarizes the available murine models for studying HIV-1 infection with an emphasis on our experience of the HIV-1-infected-cell challenge as a model for evaluating candidate HIV-1 vaccines. In the cell-based challenge model, several important factors that, hopefully, can be related to vaccine efficacy in humans were discovered: the efficiency of combining plasmid DNA representing several of the viral genes originating from multiple clades of HIV-1, the importance of adjuvants activating innate and induced immunity and the enhanced HIV eradication by drug-conjugated antibody. © 2008 Future Drugs Ltd.
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| 3. |
- Boberg, Andreas, et al.
(författare)
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Receptor binding by cholera toxin B-subunit and amino acid modification improves minimal peptide immunogenecity
- 2012
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Ingår i: ISRN Molecular Biology. - : Hindawi Publishing Corporation. - 2090-7907. ; 2012
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Tidskriftsartikel (refereegranskat)abstract
- We increase our understanding of augmenting a cellular immune response, by using an HIV-1 protease-derived epitope (PR75−84), and variants thereof, coupled to the C-terminal, of the B subunit of cholera toxin (CTB). Fusion proteins were used for immunizations of HLA-A0201 transgenic C57BL/6 mice. We observed different capacities to elicit a cellular immune response by peptides with additions of five to ten amino acids to the PR epitope. There was a positive correlation between the magnitude of the elicited cellular immune response and the capacity of the fusion protein to bind GM-1. This binding capacity is affected by its ability to form natural pentamers of CTB. Our results suggest that functional CTB pentamers containing a foreign amino acid-modified epitope is a novel way to overcome the limited cellular immunogenicity of minimal peptide antigens. This way of using a functional assay as readout for improved cellular immunogenicity might become highly valuable for difficult immunogens such as short peptides (epitopes).
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| 4. |
- Rollman, Erik, et al.
(författare)
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Evaluation of immunogenicity and efficacy of combined DNA and adjuvanted protein vaccination in a human immunodeficiency virus type 1/murine leukemia virus pseudotype challenge model
- 2007
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Ingår i: Vaccine. - : Elsevier BV. - 0264-410X .- 1873-2518. ; 25:11, s. 2145-2154
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Tidskriftsartikel (refereegranskat)abstract
- A DNA plasmid encoding human immunodeficiency virus type 1 (HIV-1) env, nef and tat genes was used in mice in a prime-boost immunization regimen with the corresponding recombinant proteins. The genetic immunogen was delivered with a gene gun and the proteins were injected intramuscularly together with the adjuvant AS02A. Immunizations were followed by experimental challenge with pseudotyped HIV-1 subtype A or B virus. In an initial experiment in which animals were challenged four weeks after the final immunization, all single modality and prime-boost vaccinations resulted in a significant level of protection as compared to control animals. There was a trend for DNA-alone immunization yielding the highest protection. In a subsequent study, a late challenge was performed 19 weeks after the final immunization. All groups having received the DNA vaccine, either alone or in combination with adjuvanted protein, exhibited strong protection against HIV replication. The subtype-specific protection against the experimental HIV challenge was significantly stronger than the cross-protection. Cellular and humoral immune responses were assessed during immunization and after challenge, but without clear correlation to protection against HIV replication. The data suggest that either DNA or protein antigens alone provide partial protection against an HIV-1/MuLV challenge and that DNA immunization is essential for achieving very high levels of efficacy in this murine HIV-1 challenge model. While prime-boost combinations were more immunogenic than DNA alone, they did not appear to provide any further enhancement over DNA vaccine mediated efficacy. The DNA immunogen might prime low levels of CD8+ T cells responsible for virus clearance or possibly a yet unidentified mechanism of protection. © 2006 Elsevier Ltd. All rights reserved.
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| 5. |
- Alfsnes, Kristian, et al.
(författare)
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Retrospective meta-transcriptomic identification of severe dengue in a traveller returning from Africa to Sweden, 1990
- 2021
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Ingår i: One Health. - : Elsevier. - 2352-7714. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Pathogens associated with haemorrhagic fever commonly have zoonotic origins. The first documented imported case of likely viral severe haemorrhagic fever in Sweden occurred in 1990. Despite extensive study, no aetiological agent was identified. Following retrospective investigation with total RNA-sequencing of samples collected between 7 and 36 days from onset of symptoms we identified dengue virus 3 (DENV-3) and a human pegivirus (HPgV). We conclude that the patient likely suffered from haemorrhagic symptoms due to an atypical severe and undiagnosed dengue infection.
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| 6. |
- Beser, Jessica, et al.
(författare)
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Seroprevalence of SARS-CoV-2 in Sweden, April 26 to May 9, 2021
- 2022
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- A national point seroprevalence study of SARS-CoV-2 was conducted in Sweden in April–May 2021. In total, 2860 individuals 3 to 90 years old from a probability-based web panel were included. Results showed that an estimated 32.6% of the population in Sweden had detectable levels of antibodies, and among non-vaccinated 20.1% had detectable levels of antibodies. We tested for differences in seroprevalence between age groups and by sex and estimated seroprevalence among previously infected participants by time since reporting.
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| 7. |
- Bråve, Andreas, et al.
(författare)
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Intranasal immunization of young mice with a multigene HIV-1 vaccine in combination with the N3 adjuvant induces mucosal and systemic immune responses
- 2008
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Ingår i: Vaccine. - : Elsevier BV. - 0264-410X .- 1873-2518. ; 26:40, s. 5075-5078
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Tidskriftsartikel (refereegranskat)abstract
- One of the major challenges for the development of an HIV vaccine is to induce potent virus-specific immune responses at the mucosal surfaces where transmission of virus occurs. Intranasal delivery of classical vaccines has been shown to induce good mucosal antibody responses, but so far for genetic vaccines the success has been limited. This study shows that young individuals are sensitive to nasal immunization with a genetic vaccine delivered in a formulation of a lipid adjuvant, the Eurocine N3. Intranasal delivery of a multiclade/multigene HIV-1 genetic vaccine gave rise to vaginal and rectal IgA responses as well as systemic humoral and cellular responses. As electroporation might become the preferred means of delivering genetic vaccines for systemic HIV immunity, nasal delivery by droplet formulation in a lipid adjuvant might become a means of priming or boosting the mucosal immunity. © 2008 Elsevier Ltd. All rights reserved.
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| 8. |
- Bråve, Andreas, et al.
(författare)
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Maternal immune status influences HIV-specific immune responses in pups after DNA prime protein boost using mucosal adjuvant
- 2008
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Ingår i: Vaccine. - : Elsevier BV. - 0264-410X .- 1873-2518. ; 26:47, s. 5957-5966
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Tidskriftsartikel (refereegranskat)abstract
- This study was designed to determine the impact of maternal HIV-1 specific immunity on HIV-DNA immunization of 2 weeks old pups during the breast-feeding period. Adult female mice received intranasal or intradermal HIV DNA (gp160Env, p37Gag, Nef, Tat and Rev) prime and recombinant protein booster immunizations that induced mucosal and systemic HIV-1 specific B and T cell responses. Intranasal administration of the immunogens induced higher serum IgG titers to HIV antigens than the intradermal immunization. Furthermore, predominantly higher HIV-1 specific fecal IgA titers were obtained in nasally immunized mice. The capacity to respond to one single prime with DNA and one boost with recombinant protein was then compared in pups born to mothers displaying HIV-1-specific immune responses and in pups born to non-vaccinated mothers. Immune responses to the greatest number of antigens were detected in pups born to mothers having the highest HIV-1 specific immune responses. These data suggest that HIV-1 DNA-plasmid immunization during breast-feeding and recombinant protein boosting shortly thereafter enhances the breadth of the humoral HIV-1 specific immune responses.
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| 9. |
- Bråve, Andreas
(författare)
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Prime-boost immunization strategies against HIV-1
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Since the start of the global HIV epidemic in 1981, more than twentyfive million people have succumbed to AIDS-related diseases. The epidemic is most severe in Sub-Saharan Africa, where twentyfive million people are currently infected and more than two million died during 2006. An indication of the epidemic s severity is that every hour the virus infects between 300 and 800 people. It is clear that an effective prophylactic vaccine is desperately needed. Attempts to utilize classical vaccine strategies against HIV-1 have proven inefficient or potentially harmful and researchers have therefore been obliged to explore novel vaccine approaches. Genetic immunization is a new way of inducing immune responses against antigens deriving from microbial pathogens or tumors. The gene encoding the antigen of interest is introduced into the body by means of an expression vector, which commonly is a recombinant bacterial plasmid or an attenuated recombinant microbe. This method of immunization has the primary benefit of inducing an immune response that mimics the response to natural infection with an intracellular pathogen. The primary strategy we use to induce high levels of broadly reactive immune responses against HIV-1 is immunization with naked DNA encoding multiple viral antigens in combination with potent adjuvants. The immune responses that are induced against plasmid-encoded antigens can be significantly augmented by subsequently boosting with additional vaccine modalities, an immunization protocol referred to as heterologous prime boost. Specifically, we show in mice that it is possible to obtain both humoral and cellular immune responses to all plasmid-encoded HIV-1 antigens in a multi-plasmid vaccine. The cytokine granulocyte macrophage-colony stimulating factor acted as an adjuvant. We also show that spatial separation of the vaccine components could augment the immune responses to some of the included antigens. Further, the responses induced by the multi-plasmid vaccine were efficiently boosted using Modified Vaccinia virus Ankara (MVA) carrying similar, but not identical, HIV-1 genes. The MVA boost resulted in significantly increased levels of HIV-1 specific antibodies as well as extremely high levels of polyfunctional CD8+ T cell responses directed against all included HIV-1 antigens. We also show the capacity of DNA and MVA to induce long-lived vaccine-specific immunological memory. Importantly, DNA was shown capable of efficiently boosting an immune response primed almost one year earlier by the same DNA construct. Moreover, the capacity of different vaccine protocols to induce protection against a cell-based HIV-1 challenge was demonstrated in an experimental model. Protection against challenge was obtained by immunizing with plasmids encoding HIV-1 Gag, Env and Tat, either alone or by priming with the plasmids and subsequently boosting with the corresponding proteins. With one exception, all the vaccine constructs described here have been or are currently being evaluated in clinical trials. In our initial phase I trial, the multigene/multisubtype vaccine has shown great potential to induce HIV-1 specific cellular immune responses in humans that can be dramatically augmented and broadened by boosting with the recombinant MVA. This vaccine protocol is currently being evaluated in a phase I trial in Tanzania. Overall, the preclinical data presented in this thesis have translated well into immunogenicity in clinical trials.
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| 10. |
- Grahn, Anna, 1973, et al.
(författare)
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Imported case of lassa fever in Sweden with encephalopathy and sensorineural hearing deficit
- 2016
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Ingår i: Open Forum Infectious Diseases. - : Oxford University Press (OUP). - 2328-8957. ; 3:4
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Tidskriftsartikel (refereegranskat)abstract
- © The Author 2016.We describe an imported case of Lassa fever with both encephalopathy and bilateral sensorineural hearing deficit. Absence of fever during hospitalization, initially nonspecific symptoms, and onset of hearing deficit in a late stage of disease probably contributed to delayed diagnosis (14 days after admittance to hospital). The pathogenesis of neurological manifestations of Lassa fever is poorly understood and no specific treatment was given. A total of 118 personnel had close contact with the patient, but no secondary cases occurred. This case highlights the importance of considering Lassa fever as a differential diagnosis in patients with recent travel to endemic areas.
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