Engineering, production, and immunogenicity studies of a truncated form of rabies virus glycoprotein produced in Nicotiana benthamiana plant

Mammadova, Gulshan; Gürbüzaslan, Irem; Yüksel, Damla; Gun, Nilufer; Mutlu, Nedim; Hasanova, Gulnara; Mamedov, T. G.

doi:10.5455/medscience.2021.09.278

Cited by 4 publications

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“…This could be ascribed to the possibility that these antigens do not display the immunogenic epitopes in their native conformation [ 59 ] and as subunit vaccine antigens are generally small peptides, they are susceptible to proteolytic degradation which, as a result, also limits the extent of the immune response stimulated [ 60 ]. Progress has been made on the development of several plant-produced subunit vaccines recently, including those against polio [ 61 ], West Nile fever [ 62 , 63 ], rabies [ 64 ], anthrax [ 65 , 66 ] and COVID-19 [ 67 , 68 ], which are all discussed below in more detail.…”

Section: Types Of Plant-produced Vaccinesmentioning

confidence: 99%

“…Since 1967, the standard rabies vaccine used has consisted of the attenuated-type human diploid cell vaccine [ 103 ], with several other attenuated and inactivated RABV vaccines approved for human use. Due to the cost associated with the production of these vaccines in animal cell culture, Mammadova et al [ 64 ] recently investigated the efficacy of a subunit RABV vaccine produced in N. benthamiana . Following transient expression of a truncated form of the G protein (RG2), a yield of ~ 32 mg/kg fresh leaf weight of purified RG2 protein was obtained and high RG2-specific antibody titers were observed in mice following IM immunisation with two doses of 5 µg RG2 with Alhydrogel ® .…”

Section: Plant-produced Human Vaccinesmentioning

confidence: 99%

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Plant-Derived Human Vaccines: Recent Developments

2022

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The idea of producing vaccines in plants originated in the late 1980s. Initially, it was contemplated that this notion could facilitate the concept of edible vaccines, making them more cost effective and easily accessible. Initial studies on edible vaccines focussed on the use of a variety of different transgenic plant host species for the production of vaccine antigens. However, adequate expression levels of antigens, the difficulties predicted with administration of consistent doses, and regulatory rules required for growth of transgenic plants gave way to the development of vaccine candidates that could be purified and administered parenterally. The field has subsequently advanced with improved expression techniques including a shift from using transgenic to transient expression of antigens, refinement of purification protocols, a deeper understanding of the biological processes and a wealth of evidence of immunogenicity and efficacy of plant-produced vaccine candidates, all contributing to the successful practice of what is now known as biopharming or plant molecular farming. The establishment of this technology has resulted in the development of many different types of vaccine candidates including subunit vaccines and various different types of nanoparticle vaccines targeting a wide variety of bacterial and viral diseases. This has brought further acceptance of plants as a suitable platform for vaccine production and in this review, we discuss the most recent advances in the production of vaccines in plants for human use.

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Section: Types Of Plant-produced Vaccinesmentioning

confidence: 99%

Section: Plant-produced Human Vaccinesmentioning

confidence: 99%

Plant-Derived Human Vaccines: Recent Developments

2022

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“…The plant transient expression system is one of the promising expression platforms for the production of various recombinant proteins, including vaccine, therapeutic proteins, and antibodies [22][23][24][25][26][27][28][29][30][31][32][33][34]. This system has a number of advantages including safety, fast, high production capacity, and easy scalability.…”

Section: Introductionmentioning

confidence: 99%

Immunogenicity and efficacy studies of Endo H in vivo deglycosylated Protective Antigen from Bacillus anthracis as a vaccine candidate against anthrax

Mamedov,

Gun,

Gulec

et al. 2024

Preprint

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Protective antigen (PA) of B. anthracis is a key component of the anthrax toxin and have been demonstrated as a main immunogenic in the development of subunit vaccine against anthrax. However, the use of recombinant PA (rPA) as a vaccine candidate has faced challenges due to its inherent chemical instability, associated with the spontaneous deamidation of multiple asparagine (Asn) residues in PA molecule. We hypothesized that Endo H in vivo deglycosylated PA83 (dPA83(E)) may be an ideal candidate for PA83-based vaccine development because this technology could eliminate the deamidation of asparagine residues in the PA83 molecule and allow the production of PA83 protein in a deglycosylated, native-like form. In this study, we conducted immunogenicity and challenge efficacy studies of dPA83(E) antigen. We show that plant-produced dPA83(E) antigen demonstrated superior properties over PNGase F in vivo deglycosylated or glycosylated PA83 counterparts and elicited high toxin neutralizing antibody titers in mice and guinea pigs. Furthermore, a single administration of this vaccine candidate protected guinea pigs 100% from fatal B. anthracis infection. Taken together, our results demonstrate that Endo H in vivo enzymatic deglycosylated PA83 is a promising candidate for the development of cost-effective, safe, stable, and highly immunogenic vaccine against anthrax.

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“…Plant-based production systems offer several advantages over traditional microbial or mammalian expression systems, such as scalability, low production costs, ease of cultivation, reduced risk of contamination with animal pathogens, and eukaryotic-type posttranslational modifications that are similar to those in human cells. Plant expression systems have been successfully utilized for the cost-effective and rapid production of wide-range recombinant proteins, such as vaccine candidates ( Farrance et al., 2011 ; Mamedov et al., 2012 ; Tottey et al., 2018 ; Wang et al., 2019 ; Shanmugaraj et al., 2020 ; Tottey et al., 2023 ; Mamedov and Yusibov, 2013 ; Mamedov et al., 2017 ; Mamedov et al., 2019a ; Mamedov et al., 2019b ; Mamedov et al., 2021a ; Mamedov et al., 2021b ; Mamedov et al., 2021c ; Mammadova et al., 2022 ), therapeutic proteins, enzymes ( Mamedov et al., 2021c ), monoclonal antibodies, clotting ( Mamedov et al., 2019a ), and growth factors and other valuable products. The plant expression system has been used for production several vaccine candidates against COVID-19 ( Capell et al., 2020 ; Shanmugaraj et al., 2020 ; Gobeil et al., 2021 ; Mamedov et al., 2021a ; Mamedov et al., 2021b ; Royal et al, 2021 ; Shanmugaraj et al., 2021 ; Siriwattananon et al., 2021 ; Ward et al., 2021 ; Hager et al., 2022 ; Moon et al., 2022 ; Pillet et al., 2022 ; Ruocco and Strasser, 2022 ; Mamedov et al., 2023 ; O'Kennedy et al., 2023 ).…”

Section: Introductionmentioning

confidence: 99%

SARS-CoV-2 spike protein S1 subunit induces potent neutralizing responses in mice and is effective against Delta and Omicron variants

Mamedov,

Yuksel,

Gurbuzaslan

et al. 2023

Front. Plant Sci.

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SARS-CoV-2, the virus responsible for the COVID-19 pandemic, belongs to the betacoronavirus genus. This virus has a high mutation rate, which rapidly evolves into new variants with different properties, such as increased transmissibility or immune evasion. Currently, the most prevalent global SARS-CoV-2 variant is Omicron, which is more transmissible than previous variants. Current available vaccines may be less effective against some currently existing SARS-CoV-2 variants, including the Omicron variant. The S1 subunit of the spike protein of SARS-CoV-2 has been a major target for COVID-19 vaccine development. It plays a crucial role in the virus’s entry into host cells and is the primary target for neutralizing antibodies. In this study, the S1 subunit of the spike protein of SARS-CoV-2 was engineered and produced at a high level in Nicotiana benthamiana plant. The expression level of the recombinant S1 protein was greater than the 0.5-g/kg fresh weight, and the purification yield was at least ~0.3 g of pure protein/kg of plant biomass, which would make a plant-produced S1 antigen an ideal vaccine candidate for commercialization. Purified, the plant-produced SARS-CoV-2 S1 protein exhibited significantly higher binding to the SARS-CoV-2 receptor, angiotensin-converting enzyme 2 (ACE2). Moreover, we also show that recombinant S1 protein/antigen-elicited antibodies can neutralize the Delta or Omicron variants. Collectively, our results demonstrate that a plant-produced S1 antigen could be a promising vaccine candidate against SARS-CoV-2 variants including Omicron.

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Engineering, production, and immunogenicity studies of a truncated form of rabies virus glycoprotein produced in Nicotiana benthamiana plant

Cited by 4 publications

References 0 publications

Plant-Derived Human Vaccines: Recent Developments

Plant-Derived Human Vaccines: Recent Developments

Immunogenicity and efficacy studies of Endo H in vivo deglycosylated Protective Antigen from Bacillus anthracis as a vaccine candidate against anthrax

SARS-CoV-2 spike protein S1 subunit induces potent neutralizing responses in mice and is effective against Delta and Omicron variants

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