Immunogenicity of adjuvanted plant-produced SARS-CoV-2 Beta spike VLP vaccine in New Zealand white rabbits

O’Kennedy, Martha M.; Abolnik, Célia; Smith, Tanja; Motlou, Thopisang; Goosen, Kruger; Sepotokele, Kamogelo M.; Roth, Robyn; Preez, Ilse du; Truyts, Alma; Stark, Hester C; Magwaza, Martin; Mahanjana, Osborn; Verschoor, J.A.; Moore, Penny L.; Lemmer, Yolandy

doi:10.1016/j.vaccine.2023.02.050

Cited by 8 publications

(7 citation statements)

References 34 publications

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“…Plant biopharming is acknowledged for its scalability, speed, versatility and low production costs and is an increasingly promising molecular pharming platform for both human and veterinary vaccines [ 32 ]. In this study, we demonstrated N .…”

Section: Discussionmentioning

confidence: 99%

Immunogenic profile of a plant-produced nonavalent African horse sickness viral protein 2 (VP2) vaccine in IFNAR-/- mice

O’Kennedy,

Roth,

Ebersohn

et al. 2024

PLoS ONE

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A safe, highly immunogenic multivalent vaccine to protect against all nine serotypes of African horse sickness virus (AHSV), will revolutionise the AHS vaccine industry in endemic countries and beyond. Plant-produced AHS virus-like particles (VLPs) and soluble viral protein 2 (VP2) vaccine candidates were developed that have the potential to protect against all nine serotypes but can equally well be formulated as mono- and bi-valent formulations for localised outbreaks of specific serotypes. In the first interferon α/β receptor knock-out (IFNAR-/-) mice trial conducted, a nine-serotype (nonavalent) vaccine administered as two pentavalent (5 μg per serotype) vaccines (VLP/VP2 combination or exclusively VP2), were directly compared to the commercially available AHS live attenuated vaccine. In a follow up trial, mice were vaccinated with an adjuvanted nine-serotype multivalent VP2 vaccine in a prime boost strategy and resulted in the desired neutralising antibody titres of 1:320, previously demonstrated to confer protective immunity in IFNAR-/- mice. In addition, the plant-produced VP2 vaccine performed favourably when compared to the commercial vaccine. Here we provide compelling data for a nonavalent VP2-based vaccine candidate, with the VP2 from each serotype being antigenically distinguishable based on LC-MS/MS and ELISA data. This is the first preclinical trial demonstrating the ability of an adjuvanted nonavalent cocktail of soluble, plant-expressed AHS VP2 proteins administered in a prime-boost strategy eliciting high antibody titres against all 9 AHSV serotypes. Furthermore, elevated T helper cells 2 (Th2) and Th1, indicative of humoral and cell-mediated memory T cell immune responses, respectively, were detected in mouse serum collected 14 days after the multivalent prime-boost vaccination. Both Th2 and Th1 may play a role to confer protective immunity. These preclinical immunogenicity studies paved the way to test the safety and protective efficacy of the plant-produced nonavalent VP2 vaccine candidate in the target animals, horses.

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Section: Discussionmentioning

confidence: 99%

Immunogenic profile of a plant-produced nonavalent African horse sickness viral protein 2 (VP2) vaccine in IFNAR-/- mice

O’Kennedy,

Roth,

Ebersohn

et al. 2024

PLoS ONE

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“…The ongoing advancements in plant biotechnology continue to expand the possibilities for utilizing plant-based production systems in various applications within the field of biotechnology and medicine. Using plant expression system, RBD and a VLP-based vaccine candidate against SARS-CoV-2 variants were developed by different research groups ( Mamedov et al., 2021a ; Mamedov et al., 2021b ; Royal et al, 2021 ; Shanmugaraj et al., 2021 ; Moon et al., 2022 ; Song et al., 2022 ; Mamedov et al., 2023 ; O'Kennedy et al., 2023 ). A number of plant-derived SARS-CoV-2 RBD-based antigens and VLPs are in preclinical and clinical trials ( Gobeil et al., 2021 ; Shanmugaraj et al., 2021 ; Ward et al., 2021 ; Hager et al., 2022 ; Pillet et al., 2022 ; Ruocco and Strasser, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

“…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 ). However, with the exception of our recent work ( Mamedov et al., 2023 ), there has been no report of efficacy of these candidate vaccines against the Omicron variant.…”

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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“…Although the progress of plant-produced vaccines is slow, the promising results of COVIFENZ ® and other plant-derived candidate vaccines against influenza and Zika virus in recent years encourage the expectation of the commercialization of many more plant-derived vaccines in the upcoming decade. Pre-clinicaltrial [190] * Transient expression in Nicotiana benthamiana (N.B. ).…”

Section: Production Of Vlp Vaccines In Plantsmentioning

confidence: 99%

“…Panapitakkul et al [ 189 ] investigated the immunogenic response of a plant-produced S1 subunit protein of SARS-CoV-2 in mice and found that it elicited robust immune responses. O’Kennedy et al [ 190 ] evaluated the immunogenicity of a plant-produced SARS-CoV-2 Beta spike VLP vaccine in rabbits and observed significant antibody responses. Mamedov et al [ 191 ] produced and characterized nucleocapsid and RBD cocktail antigens of SARS-CoV-2 in Nicotiana benthamiana plants, demonstrating their potential as vaccine candidates against COVID-19.…”

Section: Why Is a Plant-based Platform Preferred For Vaccine Producti...mentioning

confidence: 99%

Exigency of Plant-Based Vaccine against COVID-19 Emergence as Pandemic Preparedness

2023

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After two years since the declaration of COVID-19 as a pandemic by the World Health Organization (WHO), more than six million deaths have occurred due to SARS-CoV-2, leading to an unprecedented disruption of the global economy. Fortunately, within a year, a wide range of vaccines, including pathogen-based inactivated and live-attenuated vaccines, replicating and non-replicating vector-based vaccines, nucleic acid (DNA and mRNA)-based vaccines, and protein-based subunit and virus-like particle (VLP)-based vaccines, have been developed to mitigate the severe impacts of the COVID-19 pandemic. These vaccines have proven highly effective in reducing the severity of illness and preventing deaths. However, the availability and supply of COVID-19 vaccines have become an issue due to the prioritization of vaccine distribution in most countries. Additionally, as the virus continues to mutate and spread, questions have arisen regarding the effectiveness of vaccines against new strains of SARS-CoV-2 that can evade host immunity. The urgent need for booster doses to enhance immunity has been recognized. The scarcity of “safe and effective” vaccines has exacerbated global inequalities in terms of vaccine coverage. The development of COVID-19 vaccines has fallen short of the expectations set forth in 2020 and 2021. Furthermore, the equitable distribution of vaccines at the global and national levels remains a challenge, particularly in developing countries. In such circumstances, the exigency of plant virus-based vaccines has become apparent as a means to overcome supply shortages through fast manufacturing processes and to enable quick and convenient distribution to millions of people without the reliance on a cold chain system. Moreover, plant virus-based vaccines have demonstrated both safety and efficacy in eliciting robust cellular immunogenicity against COVID-19 pathogens. This review aims to shed light on the advantages and disadvantages of different types of vaccines developed against SARS-CoV-2 and provide an update on the current status of plant-based vaccines in the fight against the COVID-19 pandemic.

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Immunogenicity of adjuvanted plant-produced SARS-CoV-2 Beta spike VLP vaccine in New Zealand white rabbits

Cited by 8 publications

References 34 publications

Immunogenic profile of a plant-produced nonavalent African horse sickness viral protein 2 (VP2) vaccine in IFNAR-/- mice

Immunogenic profile of a plant-produced nonavalent African horse sickness viral protein 2 (VP2) vaccine in IFNAR-/- mice

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

Exigency of Plant-Based Vaccine against COVID-19 Emergence as Pandemic Preparedness

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