China
Africa
Explore chapters and articles related to this topic
Microbial Pathways of Lipid A Biosynthesis
Published in Helmut Brade, Steven M. Opal, Stefanie N. Vogel, David C. Morrison, Endotoxin in Health and Disease, 2020
Paul D. Rick, Christian R. H. Raetz
The recently determined genomic sequence of the hyperthermophilic bacterium, Aquifex aeolicus, is especially provacative from an evolutionary perspective (148). A. aeolicus, an organism isolated from hot springs, grows at 95°C under pressure on a mixture of H2, C02, and 02. Ribosomal RNA sequencing indicates that A. aeolicus diverged very early during the evolution of bacteria from the Archaea and Eukaryotae. Although no actual biochemical studies of LPS have been done using the Aquifex system, the fact that many of the genes encoding the enzymes of lipid A, Kdo, heptose, and outer core biosynthesis are well conserved suggests that lipid A appeared very early during membrane evolution. Presumably, outer membranes helped early bacterial species survive in hostile environments. Whatever the explanation, the availability of thermo-stabile variants of the enzymes of lipid A biosynthesis should greatly facilitate the preparation of lipid A analogs that are not readily accessible by chemical synthesis. The complete characterization of lipid A biosyn-thesis in diverse bacterial systems, including its underlying molecular and structural biology, will also enable the preparation of novel, radioactive endotoxin-like molecules with which to probe for lipid A receptors in animal systems.
Success of nano-vaccines against COVID-19: a transformation in nanomedicine
Published in Expert Review of Vaccines, 2022
Manoj Kumar Sarangi, Sasmita Padhi, Gautam Rath, Sitansu Sekhar Nanda, Dong Kee Yi
Ferritin, along with other self-assembling protein NPs platforms, is under consideration for the delivering SARS-CoV-2 immunogens. A study showed that an Aquifex aeolicus lumazine synthase (LuS) of 60 subunits and containing S through SpyTag/SpyCatcher was immunogenic in mice. The S-LuS NPs (0.08 mg) provoked a comparable nAb response to that by prototypic S protein vaccine (2.0 mg), resulting in a significant dose-sparing effect [104]. The surface of RBD-based bacteriophage capsid-like particles (RBD-CLP) using the SpyTag/Spy Catcher system allows for a high density and unidirectional display of antigens (RBD vaccine) [105]. The CLP-RBD vaccine with squalene-water-emulsion adjuvant stimulated nAb titers greater than those of the soluble RBD (single-dose vaccination of mice) and convalescent human plasma in COVID-19, and the titer can be improved further by the administration of a booster dose.
The current and future role of nanovaccines in HIV-1 vaccine development
Published in Expert Review of Vaccines, 2021
Christopher P. Karch, Gary R. Matyas
Env and Env derivatives have also been displayed on naturally occurring protein assemblies to elicit NAbs [81]. One approach has been to use ferritin nanoparticles, which are naturally occurring iron binding nanocages composed of 24 different monomers that self-assemble [97]. Presenting Env as a SOSIP on ferritin nanoparticles increases its immunogenicity over the matching soluble SOSIP; however, it did not always significantly increase neutralization [74,98,99]. This could be related to the sequence of the SOSIP or to the fact that only eight timers are presented on the ferritin nanovaccine [81]. Another naturally occurring protein assembly, lumazine synthase from Aquifex aeolicus, also self-assembles from 60 monomers to form a nanoparticle that presents 20 trimers [100]. These particles have been decorated with the outer domain (eOD) of gp120, which was engineered to stimulate the predicted germ-line precursors of VRC01 type bNAbs [101]. Transgenic mice could raise broadly neutralizing antibodies after vaccination and this candidate is currently waiting to be tested Phase I clinical trials [81,102].
Strategies for inducing effective neutralizing antibody responses against HIV-1
Published in Expert Review of Vaccines, 2019
Iván del Moral-Sánchez, Kwinten Sliepen
Multimerization of Env glycoproteins on viral-resembling particles has also been achieved by their fusion to bacterial self-assembling proteins, like ferritin from Helicobacter pylori, E2 protein from Geobacillus stearothermophilus and lumazine synthase from Aquifex aeolicus [200,201]. BG505.SOSIP antigens presented on ferritin nanoparticles induced stronger neutralizing responses than their soluble trimer counterparts in rabbits [202,203]. The autologous Tier 2 responses were not significantly increased, but the Tier 1A responses were, probably due to the presentation of linear V3 epitopes on non-native Env forms on ferritin particles [202]. However, a next generation of synthetic two-component nanoparticles can be used to present only well-folded Env trimers [204]. Using a two-component system, one could first purify the soluble Env trimers using specific quaternary specific bNAbs followed by addition of a second component to induce nanoparticle formation in vitro. This system has recently been used with success for generating RSV F nanoparticle vaccines and is thus a promising platform for HIV-1 Env trimers as well [204–206].