Immunogenicity of a subunit vaccine against Bacillus anthracis

Chichester, Jessica A.; Musiychuk, Konstantin; Rosa, Patricia de la; Horsey, April; Stevenson, Natalie; Ugulava, Natalia; Rabindran, Shailaja; Palmer, Gene A.; Mett, Vadim; Yusibov, Vidadi

doi:10.1016/j.vaccine.2007.01.068

Cited by 71 publications

(42 citation statements)

References 12 publications

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“…The most advanced transient expression system is based on the use of 'launch vectors' that combine components of plant viruses and binary plasmids, and are delivered by agroinfiltration 17,18 . Agroinfiltration of a launch vector based on Tobacco mosaic virus (TMV) has been successfully applied at lab scale to produce vaccine antigens against pathogens such as human papilloma virus 19 , Yersinia pestis 20 , influenza viruses A 21,22 , Bacillus anthracis 23 , and smallpox virus 24 in N. benthamiana leaves. Agrobacterium-mediated transient expression is also a promising method for the simultaneous production of multiple proteins 2, [25][26][27] .…”

Section: Introductionmentioning

confidence: 99%

Optimization and Utilization of Agrobacterium-mediated Transient Protein Production in Nicotiana

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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Section: Introductionmentioning

confidence: 99%

Optimization and Utilization of Agrobacterium-mediated Transient Protein Production in Nicotiana

Shamloul

Trusa

Mett

et al. 2014

JoVE

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“…Ongoing research is also focused on the design and testing of vaccines targeting antigens other than PA in an effort to broaden the breadth of immunity induced through vaccination (8,15,30,40). This was motivated in part by the realization, informed primarily by analysis of PA-specific monoclonal antibodies (MAbs) in mice and humans, that the antibody specificities responsible for LeTx neutralization may be limited to only a few dominant specificities (1,7,28,29,44).…”

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confidence: 99%

Synthetic Peptide Vaccine Targeting a Cryptic Neutralizing Epitope in Domain 2 ofBacillus anthracisProtective Antigen

Oscherwitz

Jacobs

et al. 2009

Infect Immun

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Current evidence suggests that protective antigen (PA)-based anthrax vaccines may elicit a narrow neutralizing antibody repertoire, and this may represent a vulnerability with PA-based vaccines. In an effort to identify neutralizing specificities which may complement those prevalent in PA antiserum, we evaluated whether sequences within the 2␤2-2␤3 loop of PA, which are apparent in the crystal structure of heptameric but not monomeric PA, might represent a target for an epitope-specific vaccine for anthrax and, further, whether antibodies to these sequences are induced in rabbits immunized with monomeric PA. We evaluated the immunogenicity in rabbits of a multiple antigenic peptide (MAP) displaying copies of amino acids (aa) 305 to 319 of this region. Overall, four out of six rabbits vaccinated with the MAP peptide in Freund's adjuvant developed high-titer, high-avidity antibody responses which cross-reacted with the immobilized peptide sequence comprising aa 305 to 319 and with PA, as determined by an enzyme-linked immunosorbent assay, and which displayed potent and durable neutralization of lethal toxin (LeTx) in vitro, with peak titers which were 452%, 100%, 67%, and 41% of the peak neutralization titers observed in positive-control rabbits immunized with PA. Importantly, analysis of sera from multiple cohorts of rabbits with high-titer immunity to PA demonstrated a virtual absence of this potent antibody specificity, and work by others suggests that this specificity may be present at only low levels in primate PA antiserum. These results highlight the potential importance of this immunologically cryptic neutralizing epitope from PA as a target for alternative and adjunctive vaccines for anthrax.

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“…Inhibition of receptor binding of both PA83 to the target cell and LF/EF to PA63 has been proposed as the primary mechanism of action for neutralizing antibodies. Vaccines based solely on PA domain 4 (cell receptor binding domain) have been reported to effectively protect mice from LeTx challenge (31,32). However, despite the fact that domain 4 was the most frequently targeted domain among the hMAbs where domain specificity could be established, none of the neutralizing hMAbs from this donor bound domain 4 or blocked receptor binding.…”

Section: Discussionmentioning

confidence: 99%

Generation and Characterization of Human Monoclonal Antibodies Targeting Anthrax Protective Antigen following Vaccination with a Recombinant Protective Antigen Vaccine

Chi

Liu

et al. 2015

Clin. Vaccine Immunol.

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The anthrax protective antigen (PA) is the central component of the three-part anthrax toxin, and it is the primary immunogenic component in the approved AVA anthrax vaccine and the "next-generation" recombinant PA (rPA) anthrax vaccines. Animal models have indicated that PA-specific antibodies (AB) are sufficient to protect against infection with Bacillus anthracis. In this study, we investigated the PA domain specificity, affinity, mechanisms of neutralization, and synergistic effects of PA-specific antibodies from a single donor following vaccination with the rPA vaccine. Antibody-secreting cells were isolated 7 days after the donor received a boost vaccination, and 34 fully human monoclonal antibodies (hMAb) were identified. Clones 8H6, 4A3, and 22F1 were able to neutralize lethal toxin (LeTx) both in vitro and in vivo. Clone 8H6 neutralized LeTx by preventing furin cleavage of PA in a dose-dependent manner. Clone 4A3 enhanced degradation of nicked PA, thereby interfering with PA oligomerization. The mechanism of 22F1 is still unclear. A fourth clone, 2A6, that was protective only in vitro was found to be neutralizing in vivo in combination with a toxin-enhancing antibody, 8A7, which binds to domain 3 of PA and PA oligomers. These results provide novel insights into the antibody response elicited by the rPA vaccine and may be useful for PA-based vaccine and immunotherapeutic cocktail design.

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Immunogenicity of a subunit vaccine against Bacillus anthracis

Cited by 71 publications

References 12 publications

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

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

Synthetic Peptide Vaccine Targeting a Cryptic Neutralizing Epitope in Domain 2 ofBacillus anthracisProtective Antigen

Generation and Characterization of Human Monoclonal Antibodies Targeting Anthrax Protective Antigen following Vaccination with a Recombinant Protective Antigen Vaccine

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