Order Martellivirales: Bromoviridae
Paul Pumpens, Peter Pushko, Philippe Le Mercier in Virus-Like Particles, 2022
Alfalfa mosaic virus (AMV) is the only member of the Alfamovirus genus. As mentioned earlier, the native AMV particles are bacilliform, which is a rare occasion among plant viruses. Bol et al. (1971) demonstrated that the N-terminus of the AMV coat of 221 aa residues is located on the surface of the virions and does not interfere with virus assembly. When the N-terminus of the AMV coat was removed by mild trypsin treatment, the particles lost their bacilliform shape and became spherical (Bol et al. 1974). If the particles were completely disrupted by salt, reassociation of the bacilliform particles was not possible in vitro (Hull 1970). In the presence of various RNA or DNA molecules, the AMV coat aggregated into spherical or ovoid particles or into tubular particles with lengths characteristic of the nucleic acid (Hull 1970; Driedonks et al. 1977, 1978). In the absence of RNA, the AMV coat dimers self-assembled to form empty T = 1 icosahedral particles, which have been crystallized (Fukuyama et al. 1981) and resolved by x-ray diffraction to 4.5 Å (Fukuyama et al. 1983). This structure was reprocessed to 4.0-Å resolution, which allowed the tracing of the polypeptide chain of the coat confirming the β-sandwich fold and provided information on intersubunit interactions in the particle (Kumar et al. 1997). In this study, the particle structure was also determined by the electron cryomicroscopy and image reconstruction methods and found to be in excellent agreement with the x-ray model. Figure 17.3 presents this structure, together with the 3D structures of other members of the Bromoviridae family.
Particles
Paul Pumpens in Single-Stranded RNA Phages, 2020
Concerning foreign non-coat proteins, Dunker and Anderson (1975) tried the binding of the gene-5 protein from the filamentous phage fd to the R17 RNA and found it several hundred-fold weaker than the binding to the fd DNA. As to other phage proteins, Suau et al. (1980) studied the interaction of the MS2 RNA with the phage T4 coded 32-protein (P32), the first of the group of proteins which bound tightly wto single-stranded DNA. Concerning plant viruses, the coat proteins of tobacco streak virus, brome mosaic virus, cucumber mosaic virus, and southern bean mosaic virus recognized specific sites on alfalfa mosaic virus RNA 1, but not on the MS2 RNA (Zuidema and Jaspars 1985).
Modern vaccine strategies for emerging zoonotic viruses
Published in Expert Review of Vaccines, 2022
Atif Ahmed, Muhammad Safdar, Samran Sardar, Sahar Yousaf, Fiza Farooq, Ali Raza, Muhammad Shahid, Kausar Malik, Samia Afzal
The major strategies used to produce plant-based vaccines are nuclear, transplastomic, and viral vector transformation. Nuclear transformation is a very simple and widely used method because the foreign antigen is inserted into the nuclear genome. Agrobacterium tumefaciens or gene gun-mediated transformation is used for gene transfer. The nuclear transformation results in the continuous production of recombinant proteins. Additionally, nuclear transformation also results in the post-translational modification that takes place in eukaryotic systems [93,94]. But it is also coupled with some disadvantages including, lower expression level, gene silencing, position effect, and a chance of contamination. The chloroplast transformation overcomes some of the drawbacks of nuclear transformation, which has hampered commercialization as a plant-based recombinant vaccine. The desired gene (for an antigen) is directly introduced into the genome of the plant chloroplast by using a particle cannon. Most of the currently reported edible vaccines were produced by this method because of the high stability in gene expression. In chloroplasts, many viral antigens like rotavirus and canine parvovirus were expressed. Through overcoat and epic at technologies, several viruses such as cowpea mosaic virus (CPMV), alfalfa mosaic virus, tobacco mosaic virus (TMV), cauliflower mosaic virus (CaMV), tomato bushy stunt virus, and potato virus are designed to express the part of antigenic protein on their surface as reviewed in [95].
Malaria transmission-blocking vaccines: wheat germ cell-free technology can accelerate vaccine development
Published in Expert Review of Vaccines, 2019
Kazutoyo Miura, Mayumi Tachibana, Eizo Takashima, Masayuki Morita, Bernard N. Kanoi, Hikaru Nagaoka, Minami Baba, Motomi Torii, Tomoko Ishino, Takafumi Tsuboi
The results from 3 phase 1 vaccine trials (ClinicalTrials.gov numbers; NCT01434381, NCT01867463, and NCT02013687), all of which involved Pfs25-based vaccines with Alhydrogel (Alum) adjuvant, have been published in the last 4 years. Two studies were conducted using Pfs25-EPA, Pfs25 recombinant protein was conjugated with a detoxified mutant recombinant Pseudomonas aeruginosa ExoProtein A (EPA), in U.S. adults [20] or in Malian adults [21]. The other trial involved Pfs25-CP VLP (or called Pfs25 VLP-FhCMB), a chimeric non-enveloped virus-like particle (VLP) comprising Pfs25 fused to the alfalfa mosaic virus coat protein (CP), and tested in U.S. adults [22]. In contrast to the previous trial with Pfs25 formulated with Montanide ISA51 [23], the vaccine formulations were safe and no vaccine-related serious adverse event was reported in the 3 recent trials. However, the functional activity of the induced anti-Pfs25 antibodies judged by SMFA were not satisfactory. The Pfs25-EPA study in U.S. adults estimated that the EC50 (antibody concentration which gives 50% inhibition in oocyst density, % transmission-reducing activity (TRA), in SMFA) of anti-Pfs25 antibody was 57.2 μg/mL (95% confidence interval (CI); 44.7 to 76.8 μg/mL) [20], which was close to the EC50 estimate from the previous Pfs25-ISA51 study (85.6 μg/mL; 95%CI, 58.1 to 126.0 μg/mL) [24]. The geometric mean antibody level after three immunizations in the U.S. Pfs25-EPA study was only ~30 μg/mL, and barely over the EC50 level after the fourth immunization (the peak geometric mean level was 88 μg/mL) and dropped to < 60 μg/mL ~40 days after the peak. In the Malian adult trial with Pfs25-EPA on Alum, significant, but only minor differences in % TRA was observed after the fourth immunization: median %TRA of 30 (interquartile range; 16 to 52) in a comparator vaccine group, and the median of 64 (42 to 88) in the Pfs25-EPA vaccine group [21]. In the third study with Pfs25-CP VLP, only the highest dose group (100 μg) showed significant, but weak (median of 36.2%TRA) inhibitions after the third dose [22]. While there is no evidence that the %TRA observed in SMFA could be directly extrapolated to efficacy in the field (reducing the transmissibility from a gametocyte-infected individual to a mosquito), unless the SMFA underestimates the efficacy, further improvement is likely to be required.
Related Knowledge Centers
- Alfalfa
- Bromoviridae
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- Nucleotide
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- Plant Pathology
- Sense
- Initiation Factor