For a more complete description of our group activities, please go to our MTC home page at: http://ki.se/research/karlsson-hedestam
Short research summary
A major focus in the group is to understand the mechanisms underlying the induction of potent B cell responses with the aim to elicit broadly neutralizing antibodies against complex viral surface antigens, such as the HIV-1 envelope glycoproteins (Env). To this end we have developed methods that allow a more comprehensive characterization of vaccine-induced Env directed antibody responses elicited in vivo as well as systems to study B cell differentiation in vitro. We employ these and other methods to investigate how B cells can be manipulated to promote the elicitation of desired antibody responses. We also use viruses such as Semliki Forest virus, rotavirus and adenovirus to investigate how anti-viral T and B cell responses are induced during virus infection. By combining in vitro cell culture systems and in vivo studies, we ask which immediate anti-viral host response pathways are induced by virus infection and what consequences these events have for the establishment of long-lived immune responses against virus-encoded antigens.
Selected Publications
 | A. Mörner, I. Douagi, M. N. E. Forsell, C. Sundling, P. Dosenovic, S. O dell, B. Dey, P. Kwong, G. Voss, R. Thorstensson, J. Mascola, R. Wyatt and G. B. Karlsson Hedestam "HIV-1 Env-trimer immunization of macaques and impact of priming with viral vector or stabilized core protein" (2008) J. Virol. In Press
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| C. Sundling, K. Schön, A. Mörner, M. N. E. Forsell, R. T. Wyatt, R. Thorstensson, G. B. Karlsson Hedestam and N. Y. Lycke "CTA1-DD adjuvant promotes strong immunity against human immunodeficiency virus type 1 envelope glycoproteins following mucosal immunization" (2008) J Gen Virol ; 89: 2954 2964
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| M. N. Forsell, B. Dey, A. Mörner, K. Svehla, S. O'dell, C. M. Högerkorp, G. Voss, R. Thorstensson, G. M. Shaw, J. R. Mascola, G. B. Karlsson Hedestam, R. T. Wyatt "B cell recognition of the conserved HIV-1 co-receptor binding site is altered by endogenous primate CD4." PLoS Pathog. 2008 Oct 3;4(10):e1000171.
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| G. B. Karlsson Hedestam, R. A. M. Fouchier, S. Phogat, D. R. Burton, J. Sodroski and R. T. Wyatt. "The challenges of eliciting neutralizing antibodies to HIV-1 and to influenza virus" (2008) Nat Rev Microbiol. Feb;6(2):143-55
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| M. Högbom, R. Collins, S. van den Berg, R-M. Jenvert, T. Karlberg, T. Kotenyova, A. Flores, G. B. Karlsson Hedestam and L. Holmberg Schiavone "Crystal Structure of the conserved core of the human DEAD-box helicase DDX3X in complex with the mononucleotide AMP" (2007) J. Mol. Biol.372;150-159
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| M. N. E. Forsell, G. McInerney, P. Dosenovic, Å. S. Hidmark, C. Eriksson, P. Liljeström, C. Grundner and G. B. Karlsson Hedestam “Increased HIV-1 Env expression and antibody induction using an enhanced alphavirus vector” (2007) J. Gen Virol 88:2774-2779
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| L. Breakwell, Dosenovic, P., G. B. Karlsson Hedestam, M. D'Amato, P. Liljeström, J. Fazakerley, and G. M. McInerney. “Semliki Forest virus non-structural protein 2 is involved in the suppression of the type I Interferon response.” (2007) J. Virol. 81; 8677-8684
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| S. Phogat, R.T. Wyatt and G. B. Karlsson Hedestam "Inhibition of HIV-1 entry by antibodies: potential viral and cellular targets" (2007) J. Internal Medicine. 262; 40-57
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| I. Douagi, G. McInerney, Å. S. Hidmark, V. Miriallis, K. Johansen, L. Svensson and G. B. Karlsson Hedestam “Role of IRF-3 in Type I IFN Responses in Rotavirus Infected Dendritic cells and Fibroblasts”. (2007) J. Virol. 81; 2758-2768
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| H. Sjölin, S. H. Robbins, Å. Hidmark, E. Tomasello, M. Johansson, G. Bessou, H. Hall, F. Charifi, C. A. Biron, K. G. B. Karlsson Hedestam, Kärre, P. Höglund, E. Vivier, M. Dalod “Differential regulation of Il-12 and IFNa/b production by endogenous DAP12 signalling in pDCs during viral infection in vivo” (2006) J. Immunol. 177; 2908-2916
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| Å. S. Hidmark, E. K. L. Nordström, P. Dosenovic, M. N. E. Forsell, P. Liljeström, G. B. Karlsson Hedestam "Humoral immune responses against co-administered antigen but not against alphavirus-encoded antigen require IFNa/b" (2006) J. Virol. 80; 7100-7110
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| M. Sundbäck, I. Douagi, C. Dajaray, M. N. E. Forsell, E. L. Nordström, G. McInerney, K. Spångberg, L. Tjäder, E. Bonin, M. Sundström, P. Liljeström and G. B. Karlsson Hedestam “Efficient expansion of HIV-1 specific T cell responses by homologous immunization with recombinant Semliki Forest virus particles”. (2005) Virology 341: 190-202
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| M. N. E. Forsell, Y. Li, M. Sundbäck, K. Svehla, P. Liljeström, J. Mascola, R. Wyatt and G. B. Karlsson Hedestam “Biochemical and immunogenic characterization of soluble HIV-1 envelope glycoprotein trimers expressed by Semliki Forest virus” (2005) J. Virol. 79: 10902-10914
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| Å. S. Hidmark, G. M. McInerney, E. K. L. Nordström, I. Douagi, K. M. Werner, P. Liljeström, and G. B. Karlsson Hedestam “Early IFNa/b production by myeloid dendritic cells in response to UV-treated virus requires viral entry and IRF-3, but not MyD88” (2005) J. Virol. 79; 10376-10385
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| K. A. Reimann, A. Watson, P. J. Dailey, W. Lin, C. I. Lord, T. D. Steenbeke, M. K. Axthelm, and G. B. Karlsson. “Viral burden and disease progression in rhesus monkeys infected with chimeric simian human immunodeficiency viruses.” (1999) Virology 256; 15-21
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| G. B. Karlsson, M. Halloran, D. Schenten, J. Lee, P. Racz, K. Tenner-Racz, J. Manola, R. Gelman, B. Etemad-Moghadam, E. Desjardins, R. Wyatt, N. P. Gerard, L. Marcon, D. Margolin, J. Fanton, M. K. Axthelm, N. L. Letvin, and J. Sodroski. “The envelope glycoprotein ectodomains determine the efficiency of CD4+ T-lymphocyte depletion in simian-human immunodeficiency virus-infected macaques.” (1998) J. Exp. Med. 188; 1159-1171
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| B. Etemad-Moghadam, G. B. Karlsson, M. Halloran, Y. Sun, D. Schenten, M. Fernandes, N. Letvin, and J. Sodroski.“Characterization of Simian-Human Immunodeficiency virus envelope glycoprotein epitopes recognized by neutralizing antibodies from infected monkeys” (1998) J. Virol. 72; 8437-8445
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| G. B. Karlsson, M. Halloran, J. Li, I-W. Park, R. Gomila, K. A. Reimann, M. K. Axthelm, S. A. Iliff, N. L. Letvin, and J. Sodroski. (1997) ” Characterization of molecularly cloned simian-human immunodeficiency viruses causing rapid CD4+ lymphocyte depletion in rhesus monkeys.” (1997) J. Virol. 71; 4218-4225
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| M. Farzan, H. Choe, K. Martin, L. Marcon, W. Hofmann, G. Karlsson, Y. Sun, P. Barrett, N. Marchand, N. Sullivan, N. Gerard, C. Gerard, and J. Sodroski. “Two orphan seven-transmembrane segment receptors that are expressed in CD4-positive cells support simian immunodeficinecy virus infection.” (1997) J. Exp. Med. 186; 405-411
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| G. B. Karlsson, F. Gao, J. Robinson, B. H. Hahn, and J. Sodroski. “Increased envelope spike density and stability are not required for the neutralization resistance of primary human immunodeficiency viruses.” (1996) J. Virol. 70; 6136-6142 |
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