Effect of Fusion to the LTB Carrier Protein on Coronavirus Spike Protein Vaccine Candidates Produced in Maize

Coronaviruses continue to disrupt health and economic productivity worldwide. Porcine epidemic diarrhea virus (PEDV) is a devastating swine disease and SARS-CoV-2 is the latest coronavirus to infect the human population. Both viruses display a similar spike protein on the surface that is a target of...

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Main Authors: Erin Egelkrout, Magdalena Maj, Rodrigo Manjarin, Gina Fake, Muneaki Watanabe, Jenna Williams, Nate Blanchard, John Walker, Celine Hayden, John Howard
Format: Article
Language:English
Published: MDPI AG 2024-12-01
Series:Viruses
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Online Access:https://www.mdpi.com/1999-4915/17/1/7
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author Erin Egelkrout
Magdalena Maj
Rodrigo Manjarin
Gina Fake
Muneaki Watanabe
Jenna Williams
Nate Blanchard
John Walker
Celine Hayden
John Howard
author_facet Erin Egelkrout
Magdalena Maj
Rodrigo Manjarin
Gina Fake
Muneaki Watanabe
Jenna Williams
Nate Blanchard
John Walker
Celine Hayden
John Howard
author_sort Erin Egelkrout
collection DOAJ
description Coronaviruses continue to disrupt health and economic productivity worldwide. Porcine epidemic diarrhea virus (PEDV) is a devastating swine disease and SARS-CoV-2 is the latest coronavirus to infect the human population. Both viruses display a similar spike protein on the surface that is a target of vaccine development. Despite the availability of commercial vaccines for both viruses, there is still a high occurrence of infections and a great need for enhanced efficacy and lower costs. We previously produced the PEDV spike protein (S) using transgenic maize, enabling a low-cost supply of the vaccine candidate. In this study, we (1) test orally delivered PEDV vaccine candidates in pigs to optimize the mucosal immune response; (2) generate the SARS-CoV-2 S1 protein in maize; and (3) perform structural characterization of the S1 protein for PEDV and SARS-CoV-2. We demonstrated high expression levels in maize of the S1 subunit of the SARS-CoV-2 spike protein, both with and without fusion to the heat-labile enterotoxin B (LTB) subunit. We found that the LTB fusion protein from both coronaviruses preferentially assembles into higher molecular weight multimers, consistent with the formation of trimers. For PEDV, administering the spike protein fused to LTB to young pigs elicited a higher level of mucosal IgAs compared to maize grain containing the S1 protein alone or controls. This suggests that fusing the coronavirus spike protein with LTB may provide better protection.
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spelling doaj-art-991299e750ce4d448824ee7cc2bcf1142025-01-24T13:52:14ZengMDPI AGViruses1999-49152024-12-01171710.3390/v17010007Effect of Fusion to the LTB Carrier Protein on Coronavirus Spike Protein Vaccine Candidates Produced in MaizeErin Egelkrout0Magdalena Maj1Rodrigo Manjarin2Gina Fake3Muneaki Watanabe4Jenna Williams5Nate Blanchard6John Walker7Celine Hayden8John Howard9Applied Biotechnology Institute, California Polytechnic Tech Park, San Luis Obispo, CA 93407, USADepartment of Biological Sciences, California Polytechnic State University, San Luis Obispo, CA 93407, USADepartment of Animal Sciences, California Polytechnic State University, San Luis Obispo, CA 93407, USAApplied Biotechnology Institute, California Polytechnic Tech Park, San Luis Obispo, CA 93407, USAApplied Biotechnology Institute, California Polytechnic Tech Park, San Luis Obispo, CA 93407, USADepartment of Biological Sciences, California Polytechnic State University, San Luis Obispo, CA 93407, USADepartment of Biological Sciences, California Polytechnic State University, San Luis Obispo, CA 93407, USADepartment of Statistics, California Polytechnic State University, San Luis Obispo, CA 93407, USAApplied Biotechnology Institute, California Polytechnic Tech Park, San Luis Obispo, CA 93407, USAApplied Biotechnology Institute, California Polytechnic Tech Park, San Luis Obispo, CA 93407, USACoronaviruses continue to disrupt health and economic productivity worldwide. Porcine epidemic diarrhea virus (PEDV) is a devastating swine disease and SARS-CoV-2 is the latest coronavirus to infect the human population. Both viruses display a similar spike protein on the surface that is a target of vaccine development. Despite the availability of commercial vaccines for both viruses, there is still a high occurrence of infections and a great need for enhanced efficacy and lower costs. We previously produced the PEDV spike protein (S) using transgenic maize, enabling a low-cost supply of the vaccine candidate. In this study, we (1) test orally delivered PEDV vaccine candidates in pigs to optimize the mucosal immune response; (2) generate the SARS-CoV-2 S1 protein in maize; and (3) perform structural characterization of the S1 protein for PEDV and SARS-CoV-2. We demonstrated high expression levels in maize of the S1 subunit of the SARS-CoV-2 spike protein, both with and without fusion to the heat-labile enterotoxin B (LTB) subunit. We found that the LTB fusion protein from both coronaviruses preferentially assembles into higher molecular weight multimers, consistent with the formation of trimers. For PEDV, administering the spike protein fused to LTB to young pigs elicited a higher level of mucosal IgAs compared to maize grain containing the S1 protein alone or controls. This suggests that fusing the coronavirus spike protein with LTB may provide better protection.https://www.mdpi.com/1999-4915/17/1/7PEDVSARS-CoV-2spike proteinoral deliveryplant-produced vaccinesmaize
spellingShingle Erin Egelkrout
Magdalena Maj
Rodrigo Manjarin
Gina Fake
Muneaki Watanabe
Jenna Williams
Nate Blanchard
John Walker
Celine Hayden
John Howard
Effect of Fusion to the LTB Carrier Protein on Coronavirus Spike Protein Vaccine Candidates Produced in Maize
Viruses
PEDV
SARS-CoV-2
spike protein
oral delivery
plant-produced vaccines
maize
title Effect of Fusion to the LTB Carrier Protein on Coronavirus Spike Protein Vaccine Candidates Produced in Maize
title_full Effect of Fusion to the LTB Carrier Protein on Coronavirus Spike Protein Vaccine Candidates Produced in Maize
title_fullStr Effect of Fusion to the LTB Carrier Protein on Coronavirus Spike Protein Vaccine Candidates Produced in Maize
title_full_unstemmed Effect of Fusion to the LTB Carrier Protein on Coronavirus Spike Protein Vaccine Candidates Produced in Maize
title_short Effect of Fusion to the LTB Carrier Protein on Coronavirus Spike Protein Vaccine Candidates Produced in Maize
title_sort effect of fusion to the ltb carrier protein on coronavirus spike protein vaccine candidates produced in maize
topic PEDV
SARS-CoV-2
spike protein
oral delivery
plant-produced vaccines
maize
url https://www.mdpi.com/1999-4915/17/1/7
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