| 1. |
- Giefing, C, et al.
(författare)
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Discovery of a novel class of highly conserved vaccine antigens using genomic scale antigenic fingerprinting of pneumococcus with human antibodies
- 2008
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Ingår i: The Journal of experimental medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 205:1, s. 117-131
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Tidskriftsartikel (refereegranskat)abstract
- Pneumococcus is one of the most important human pathogens that causes life-threatening invasive diseases, especially at the extremities of age. Capsular polysaccharides (CPSs) are known to induce protective antibodies; however, it is not feasible to develop CPS-based vaccines that cover all of the 90 disease-causing serotypes. We applied a genomic approach and described the antibody repertoire for pneumococcal proteins using display libraries expressing 15–150 amino acid fragments of the pathogen's proteome. Serum antibodies of exposed, but not infected, individuals and convalescing patients identified the ANTIGENome of pneumococcus consisting of ∼140 antigens, many of them surface exposed. Based on several in vitro assays, 18 novel candidates were preselected for animal studies, and 4 of them showed significant protection against lethal sepsis. Two lead vaccine candidates, protein required for cell wall separation of group B streptococcus (PcsB) and serine/threonine protein kinase (StkP), were found to be exceptionally conserved among clinical isolates (>99.5% identity) and cross-protective against four different serotypes in lethal sepsis and pneumonia models, and have important nonredundant functions in bacterial multiplication based on gene deletion studies. We describe for the first time opsonophagocytic killing activity for pneumococcal protein antigens. A vaccine containing PcsB and StkP is intended for the prevention of infections caused by all serotypes of pneumococcus in the elderly and in children.
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| 2. |
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| 3. |
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| 4. |
- Byström, Anders S, et al.
(författare)
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Differentially expressed trmD ribosomal protein operon of Escherichia coli is transcribed as a single polycistronic mRNA species
- 1989
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Ingår i: Journal of Molecular Biology. - : Academic Press. - 0022-2836 .- 1089-8638. ; 208:4, s. 575-586
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Tidskriftsartikel (refereegranskat)abstract
- The trmD operon is a four-cistron operon in which the first and fourth genes encode ribosomal proteins S16 (rpsP) and L19 (rplS), respectively. The second gene encodes a 21,000 Mr polypeptide of unknown function and the third gene (trmD) encodes the enzyme tRNA(m1G37)methyltransferase, which catalyzes the formation of 1-methylguanosine (m1G) next to the 3' end of the anticodon (position 37) of some tRNAs in Escherichia coli. Here we show under all regulatory conditions studied, transcription initiates at one unique site, and the entire operon is transcribed into one polycistronic mRNA. Between the promoter and the first gene, rpsP, an attenuator-like structure is found (delta G = -18 kcal; 1 cal = 4.184 J), followed by four uridine residues. This structure is functional in vitro, and terminates more than two-thirds of the transcripts. The different parts of the trmD operon mRNA decay at a uniform rate. The stability of the trmD mRNA is not reduced with decreasing growth rate, which is in contrast to what has been found for other ribosomal protein mRNAs. Furthermore, earlier experiments have shown the existence of differential expression as well as non-co-ordinate regulation within the operon. Our results are consistent with the regulation of the trmD operon being due to some mechanism(s) operating at the post-transcriptional level, and do not involve differential degradation of different mRNA segments, internal promoters or internal terminators.
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| 5. |
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| 6. |
- Lund, B, et al.
(författare)
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Differential expression of interferon genes in a substrain of Namalwa cells.
- 1985
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Ingår i: Journal of interferon research. - 0197-8357. ; 5:2, s. 229-38
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Tidskriftsartikel (refereegranskat)abstract
- A substrain of Namalwa cells producing a high ratio of beta-interferon (IFN-beta) versus alpha-interferon (IFN-alpha) was investigated by constructing a cDNA library after induction with Sendai virus. The library was screened by two synthetic oligonucleotides, one specific for IFN-alpha and one complementary to both IFN-alpha and IFN-beta. Rescreening the library with two full-length cDNAs encoding IFN-alpha and IFN-beta, respectively, revealed that the frequency of the IFN-alpha and IFN-beta clones reflected the activities of IFN-alpha and IFN-beta obtained by functional assays. On the cDNA level, the dominating species was identical with the type of IFN-alpha A or IFN-alpha 2; however, one new type of cDNA also was found that was similar to the previously described IFN-alpha C. Only one type of cDNA was found encoding IFN-beta, although several IFN-beta proteins have been detected in the analyzed cell line.
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| 7. |
- Lund, B, et al.
(författare)
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Novel cluster of alpha-interferon gene sequences in a placental cosmid DNA library.
- 1984
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - 0027-8424 .- 1091-6490. ; 81:8, s. 2435-9
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Tidskriftsartikel (refereegranskat)abstract
- A human cosmid library was constructed and probed with a human alpha interferon (IFN-alpha) cDNA clone. One clone giving a strong hybridizing signal was isolated and characterized. The cosmid DNA insert represents a section of the human genome containing three regions of IFN-alpha-like sequences. The DNA was characterized with restriction endonuclease mapping, thereby allowing comparison to similar linkage groups reported recently and determination of homologous regions on the known physical map. The three IFN-alpha-like sequences were analyzed by a partial sequence analysis. Mapping and sequence data establish this section as a not-yet-described cluster of IFN-alpha sequences in the human genome; however, a part of the section matches to some degree to a previously described genomic region. The region described here could represent genetic polymorphism or a duplicated segment.
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| 9. |
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| 10. |
- Singer, D, et al.
(författare)
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Interview with Professor Alex von Gabain
- 2012
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Ingår i: HEALTH POLICY AND TECHNOLOGY. - : Elsevier BV. - 2211-8837. ; 1:4, s. 228-229
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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