Human-derived, plant-produced monoclonal antibody for the treatment of anthrax

Hull, Anna K.; Criscuolo, Carolyn J.; Mett, Vadim; Groen, Herman; Steeman, Wilma; Westra, Hans; Chapman, Gail D.; Legutki, Bart; Baillie, Les; Yusibov, Vidadi

doi:10.1016/j.vaccine.2005.01.013

Cited by 77 publications

(51 citation statements)

References 13 publications

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“…Data are shown as mean serum IgG endpoint titers Ϯ standard deviations. get expression ranging from 100 mg to over 1 g/kg of fresh whole leaf tissue (7,19,23,26,40). Due to the complexity of the Pfs230 protein, we endeavored to use our transient-expression system in N. benthamiana to express the portion of Pfs230C (230CMB) that was shown to have TB activity using an in vitro translation system (40a).…”

Section: Discussionmentioning

confidence: 99%

A Plant-Produced Pfs230 Vaccine Candidate Blocks Transmission of Plasmodium falciparum

Farrance

Rhee

Jones

et al. 2011

Clin Vaccine Immunol

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Plasmodium falciparum is transmitted to a new host after completing its sexual cycle within a mosquito. Developing vaccines against the parasite sexual stages is a critical component in the fight against malaria. We are targeting multiple proteins of P. falciparum which are found only on the surfaces of the sexual forms of the parasite and where antibodies against these proteins have been shown to block the progression of the parasite's life cycle in the mosquito and thus block transmission to the next human host. We have successfully produced a region of the Pfs230 antigen in our plant-based transient-expression system and evaluated this vaccine candidate in an animal model. This plant-produced protein, 230CMB, is expressed at approximately 800 mg/kg in fresh whole leaf tissue and is 100% soluble. Administration of 230CMB with >90% purity induces strong immune responses in rabbits with high titers of transmission-blocking antibodies, resulting in a greater than 99% reduction in oocyst counts in the presence of complement, as determined by a standard membrane feeding assay. Our data provide a clear perspective on the clinical development of a Pfs230-based transmissionblocking malaria vaccine.

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Section: Discussionmentioning

confidence: 99%

A Plant-Produced Pfs230 Vaccine Candidate Blocks Transmission of Plasmodium falciparum

Farrance

Rhee

Jones

et al. 2011

Clin Vaccine Immunol

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“…Currently, there are several anti-PA monoclonal antibodies at various stages of development (14,15,21,32,37), but a direct comparison of the potencies of these antibodies in the same animal model is lacking. Two reports described antibodies that neutralize LeTx in a toxin challenge model (14,37) showed that a PA monoclonal antibody significantly improved the outcome of a lethal toxin infusion rat model when the antibody was administered at 10-fold molar excess to PA up to 6 h after initial exposure to LeTx (8).…”

Section: Discussionmentioning

confidence: 99%

Human Monoclonal Anti-Protective Antigen Antibody Completely Protects Rabbits and Is Synergistic with Ciprofloxacin in Protecting Mice and Guinea Pigs against Inhalation Anthrax

et al. 2006

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Prevention of inhalation anthrax requires early and extended antibiotic therapy, and therefore, alternative treatment strategies are needed. We investigated whether a human monoclonal antibody (AVP-21D9) to protective antigen (PA) would protect mice, guinea pigs, and rabbits against anthrax. Control animals challenged with Bacillus anthracis Ames spores by the intranasal route died within 3 to 7 days. AVP-21D9 alone provided minimal protection against anthrax in the murine model, but its efficacy was notably better in guinea pigs. When Swiss-Webster mice, challenged with five 50% lethal doses (LD 50 s) of anthrax spores, were given a single 16.7-mg/kg of body weight AVP-21D9 antibody dose combined with ciprofloxacin (30 mg/kg/day for 6 days) 24 h after challenge, 100% of the mice were protected for more than 30 days, while ciprofloxacin or AVP-21D9 alone showed minimal protection. Similarly, when AVP-21D9 antibody (10 to 50 mg/kg) was combined with a low, nonprotective dose of ciprofloxacin (3.7 mg/kg/day) and administered to guinea pigs for 6 days, synergistic protection against anthrax was observed. In contrast, a single dose of AVP-21D9 antibody (1, 5, 10, or 20 mg/kg) but not 0.2 mg/kg alone completely protected rabbits against challenge with 100 LD 50 s of B. anthracis Ames spores, and 100% of the rabbits survived rechallenge. Further, administration of AVP-21D9 (10 mg/kg) to rabbits at 0, 6, and 12 h after challenge with anthrax spores resulted in 100% survival; however, delay of antibody treatment by 24 and 48 h reduced survival to 80% and 60%, respectively. Serological analysis of sera from various surviving animals 30 days postprimary infection showed development of a species-specific PA enzyme-linked immunosorbent assay antibody titer that correlated with protection against reinfection. Taken together, the effectiveness of human anti-PA antibody alone or in combination with low ciprofloxacin levels may provide the basis for an improved strategy for prophylaxis or treatment following inhalation anthrax infection.The severest form of anthrax results from inhalation of spores from Bacillus anthracis. The organism secretes three protein toxin components encoded by the genes cya, lef, and pag located on the pX01 plasmid (6,20,23). The virulence of B. anthracis is in part attributed to two separate bacterial proteins, edema factor (EF) (encoded by the cya gene) and lethal factor (LF) (encoded by the lef gene), both of which interact with protective antigen (PA) (encoded by the pag gene), a third protein that binds to receptors (4,16,28,30) on the host cell surface, forming edema toxin and lethal toxin (LeTx). EF, an 88.9-kDa protein, is a calmodulin-dependent adenylyl cyclase enzyme, while the 90.2-kDa LF is a Zn 2ϩ metalloprotease (6, 23). The 82.7-kDa receptor-binding PA is nicked by a furin-like protease produced by target cells and heptamerizes, forming binding sites for EF and LF. The membrane-bound holotoxin is then transported into the host cell by receptor-mediated endocytosis. Acidification of the e...

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“…Agrobacterium-mediated transient expression is also a promising method for the simultaneous production of multiple proteins 2, [25][26][27] . For example, plant transient expression systems have been used to produce tumor-specific recombinant antibodies 28,29 , a glycosylated recombinant antibody against the epidermal growth factor receptor 30 , and a monoclonal antibody specific for anthrax protective antigen 31,32 . Co-infiltration of Nicotiana benthamiana plants with a target gene and a suppressor of gene silencing results in enhanced target protein expression 33,34 .…”

Section: Introductionmentioning

confidence: 99%

Optimization and Utilization of <em>Agrobacterium</em>-mediated Transient Protein Production in <em>Nicotiana</em>

Shamloul

Trusa

Mett

et al. 2014

JoVE

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Agrobacterium-mediated transient protein production in plants is a promising approach to produce vaccine antigens and therapeutic proteins within a short period of time. However, this technology is only just beginning to be applied to large-scale production as many technological obstacles to scale up are now being overcome. Here, we demonstrate a simple and reproducible method for industrial-scale transient protein production based on vacuum infiltration of Nicotiana plants with Agrobacteria carrying launch vectors. Optimization of Agrobacterium cultivation in AB medium allows direct dilution of the bacterial culture in Milli-Q water, simplifying the infiltration process. Among three tested species of Nicotiana, N. excelsiana (N. benthamiana × N. excelsior) was selected as the most promising host due to the ease of infiltration, high level of reporter protein production, and about two-fold higher biomass production under controlled environmental conditions. Induction of Agrobacterium harboring pBID4-GFP (Tobacco mosaic virus-based) using chemicals such as acetosyringone and monosaccharide had no effect on the protein production level. Infiltrating plant under 50 to 100 mbar for 30 or 60 sec resulted in about 95% infiltration of plant leaf tissues. Infiltration with Agrobacterium laboratory strain GV3101 showed the highest protein production compared to Agrobacteria laboratory strains LBA4404 and C58C1 and wild-type Agrobacteria strains at6, at10, at77 and A4. Co-expression of a viral RNA silencing suppressor, p23 or p19, in N. benthamiana resulted in earlier accumulation and increased production (15-25%) of target protein (influenza virus hemagglutinin).

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Human-derived, plant-produced monoclonal antibody for the treatment of anthrax

Cited by 77 publications

References 13 publications

A Plant-Produced Pfs230 Vaccine Candidate Blocks Transmission of Plasmodium falciparum

A Plant-Produced Pfs230 Vaccine Candidate Blocks Transmission of Plasmodium falciparum

Human Monoclonal Anti-Protective Antigen Antibody Completely Protects Rabbits and Is Synergistic with Ciprofloxacin in Protecting Mice and Guinea Pigs against Inhalation Anthrax

Optimization and Utilization of <em>Agrobacterium</em>-mediated Transient Protein Production in <em>Nicotiana</em>

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