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261.
Improved efficiency of a Salmonella-based vaccine against human papillomavirus type 16 virus-like particles achieved by using a codon-optimized version of L1 总被引:4,自引:0,他引:4 下载免费PDF全文
Baud D Ponci F Bobst M De Grandi P Nardelli-Haefliger D 《Journal of virology》2004,78(23):12901-12909
Cervical cancer results from cervical infection by human papillomaviruses (HPVs), especially HPV16. An effective vaccine against these HPVs is expected to have a dramatic impact on the incidence of this cancer and its precursor lesions. The leading candidate, a subunit prophylactic HPV virus-like particle (VLP) vaccine, can protect women from HPV infection. An alternative improved vaccine that avoids parenteral injection, that is efficient with a single dose, and that induces mucosal immunity might greatly facilitate vaccine implementation in different settings. In this study, we have constructed a new generation of recombinant Salmonella organisms that assemble HPV16 VLPs and induce high titers of neutralizing antibodies in mice after a single nasal or oral immunization with live bacteria. This was achieved through the expression of a HPV16 L1 capsid gene whose codon usage was optimized to fit with the most frequently used codons in Salmonella. Interestingly, the high immunogenicity of the new recombinant bacteria did not correlate with an increased expression of L1 VLPs but with a greater stability of the L1-expressing plasmid in vitro and in vivo in absence of antibiotic selection. Anti-HPV16 humoral and neutralizing responses were also observed with different Salmonella enterica serovar Typhimurium strains whose attenuating deletions have already been shown to be safe after oral vaccination of humans. Thus, our findings are a promising improvement toward a vaccine strain that could be tested in human volunteers. 相似文献
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K van Oers A W Santure I De Cauwer N EM van Bers R PMA Crooijmans B C Sheldon M E Visser J Slate M AM Groenen 《Heredity》2014,112(3):307-316
Linking variation in quantitative traits to variation in the genome is an important, but
challenging task in the study of life-history evolution. Linkage maps provide a valuable
tool for the unravelling of such trait−gene associations. Moreover, they give
insight into recombination landscapes and between-species karyotype evolution. Here we
used genotype data, generated from a 10k single-nucleotide polymorphism (SNP) chip, of
over 2000 individuals to produce high-density linkage maps of the great tit (Parus
major), a passerine bird that serves as a model species for ecological and
evolutionary questions. We created independent maps from two distinct populations: a
captive F2-cross from The Netherlands (NL) and a wild population from the United Kingdom
(UK). The two maps contained 6554 SNPs in 32 linkage groups, spanning 2010 cM and
1917 cM for the NL and UK populations, respectively, and were similar in size and
marker order. Subtle levels of heterochiasmy within and between chromosomes were
remarkably consistent between the populations, suggesting that the local departures from
sex-equal recombination rates have evolved. This key and surprising result would have been
impossible to detect if only one population was mapped. A comparison with zebra finch
Taeniopygia guttata, chicken Gallus gallus and the green anole lizard
Anolis carolinensis genomes provided further insight into the evolution of
avian karyotypes. 相似文献
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C.R. Toppin I.E. Thomas E.V. Bobst A.M. Bobst 《International journal of biological macromolecules》1983,5(1):33-36
The synthesis of novel spin labelled deoxynucleoside-5′-triphosphates and their enzymatic incorporation with terminal deoxynucleotidyl transferase into DNA are described. 相似文献
268.
O K Strobel R S Keyes A M Bobst 《Biochemical and biophysical research communications》1990,166(3):1435-1440
We present spectroscopic evidence for an electron paramagnetic resonance (EPR) probe to detect local Z-DNA conformations in synthetic DNA. A spin labeled deoxycytidine-5'-triphosphate (pppDCAT) was co-polymerized with Micrococcus luteus DNA polymerase to yield the spin active alternating co-polymer (dG-dC,DCAT)n. The EPR spectrum of (dG-dC,DCAT)n in the Z-DNA conformation indicates a decrease in the local base dynamics by about a factor of two as compared to that computed for B-DNA. A control experiment conducted with (dA-dT, DUAT)n under similar salt conditions rules out the possibility of observing salt induced artifacts. 相似文献
269.
Conformation detection and base dynamics of spin-labeled Z-DNA have been investigated by electron paramagnetic resonance (EPR) spectroscopy. The two synthesized and characterized probes used in this study were C(5)-nitroxide-labeled 2'-deoxycytidine 5'-triphosphates, pppDCAT and pppDCAVAT, which serve as suitable substrates for Micrococcus luteus DNA polymerase. Enzymatic incorporation of these probes into (dG-dC)n yields the EPR-active alternating copolymers (dG-dC,DCAT)n and (dG-dC,-DCAVAT)n. These polymers assume typical B- and Z-DNA conformations under respective low (0.1 M NaCl) and high (4.5 M NaCl) salt conditions, as evidenced by their UV-circular dichroism spectra. The EPR line shape of (dG-dC,DCAT)n in Z-form is unique and significantly different from the B-form EPR spectrum. A similar observation is made for (dG-dC,DCAVAT)n. Thus, the EPR line shapes of these spin-labeled DNAs are indicative of their local conformations. The EPR spectra, analyzed with a previously published motional model [Kao, S.-C., Polnaszek, C.F., Toppin, C.R., & Bobst, A.M. (1983) Biochemistry 22, 5563-5568], indicate tau perpendicular values of 4 and 7 ns for the B- and Z-forms, respectively. Therefore, the base dynamics of Z-DNA are about two times slower than in B-DNA. 相似文献
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