Newcastle Disease Virus Displaying an Ectodomain of Middle East Respiratory Syndrome Coronavirus Spike Protein Elicited Robust Humoral and Cellular Immunity in Mice

Background: Middle East Respiratory Syndrome Coronavirus (MERS-CoV) causes severe respiratory illness in humans and currently lacks an approved vaccine. The Newcastle disease virus (NDV) vector is a well-established, safe, and effective platform for vaccine development. With recent advancements in s...

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Main Authors: Jaturawitt Prasopsiri, Kanjana Srisutthisamphan, Benjamas Liwnaree, Juggragarn Jengarn, Jarin Kramyu, Payuda Hansoongnern, Papon Muangsanit, Nathiphat Tanwattana, Challika Kaewborisuth, Suttipun Sungsuwan, Anan Jongkaewwattana, Nanchaya Wanasen
Format: Article
Language:English
Published: MDPI AG 2024-12-01
Series:Vaccines
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Online Access:https://www.mdpi.com/2076-393X/13/1/2
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author Jaturawitt Prasopsiri
Kanjana Srisutthisamphan
Benjamas Liwnaree
Juggragarn Jengarn
Jarin Kramyu
Payuda Hansoongnern
Papon Muangsanit
Nathiphat Tanwattana
Challika Kaewborisuth
Suttipun Sungsuwan
Anan Jongkaewwattana
Nanchaya Wanasen
author_facet Jaturawitt Prasopsiri
Kanjana Srisutthisamphan
Benjamas Liwnaree
Juggragarn Jengarn
Jarin Kramyu
Payuda Hansoongnern
Papon Muangsanit
Nathiphat Tanwattana
Challika Kaewborisuth
Suttipun Sungsuwan
Anan Jongkaewwattana
Nanchaya Wanasen
author_sort Jaturawitt Prasopsiri
collection DOAJ
description Background: Middle East Respiratory Syndrome Coronavirus (MERS-CoV) causes severe respiratory illness in humans and currently lacks an approved vaccine. The Newcastle disease virus (NDV) vector is a well-established, safe, and effective platform for vaccine development. With recent advancements in stabilizing coronavirus spike proteins to enhance their antigenicity, this study aimed to determine whether modifications to the MERS-CoV spike protein could improve its presentation on NDV particles, allowing the resulting virus to be used as an inactivated vaccine. Methods: We codon-optimized the gene encoding the ectodomain of the MERS-CoV spike protein and incorporated modifications at the S1/S2 and S2’ cleavage sites, along with a proline substitution at residues V1060-L1061. This modified spike gene was inserted into the NDV genome to create the NDV-S<sub>MERS</sub> virus. After purification and inactivation, the vaccine’s immunogenicity was assessed in mice. Results: Mice immunized with the inactivated NDV-S<sub>MERS</sub> vaccine developed robust anti-spike IgGs, neutralizing antibodies, and cellular immune responses. The study demonstrated that modifications to the MERS-CoV spike protein were essential for its effective presentation on NDV particles. Additionally, the spike gene insert remained stable through five egg passages, confirming the vector’s stability. Conclusions: Engineering the MERS-CoV spike protein is crucial for its successful display on NDV particles. The strong immune responses elicited by the NDV-S<sub>MERS</sub> vaccine in mice highlight that NDV is a promising, safe, and effective platform for MERS-CoV vaccination.
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spelling doaj-art-8bd5f4309c554ff8b865f43e28f601492025-01-24T13:51:37ZengMDPI AGVaccines2076-393X2024-12-01131210.3390/vaccines13010002Newcastle Disease Virus Displaying an Ectodomain of Middle East Respiratory Syndrome Coronavirus Spike Protein Elicited Robust Humoral and Cellular Immunity in MiceJaturawitt Prasopsiri0Kanjana Srisutthisamphan1Benjamas Liwnaree2Juggragarn Jengarn3Jarin Kramyu4Payuda Hansoongnern5Papon Muangsanit6Nathiphat Tanwattana7Challika Kaewborisuth8Suttipun Sungsuwan9Anan Jongkaewwattana10Nanchaya Wanasen11National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Khlong Nueng, Khlong Luang, Pathum Thani 12120, ThailandNational Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Khlong Nueng, Khlong Luang, Pathum Thani 12120, ThailandNational Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Khlong Nueng, Khlong Luang, Pathum Thani 12120, ThailandNational Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Khlong Nueng, Khlong Luang, Pathum Thani 12120, ThailandNational Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Khlong Nueng, Khlong Luang, Pathum Thani 12120, ThailandNational Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Khlong Nueng, Khlong Luang, Pathum Thani 12120, ThailandNational Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Khlong Nueng, Khlong Luang, Pathum Thani 12120, ThailandNational Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Khlong Nueng, Khlong Luang, Pathum Thani 12120, ThailandNational Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Khlong Nueng, Khlong Luang, Pathum Thani 12120, ThailandNational Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Khlong Nueng, Khlong Luang, Pathum Thani 12120, ThailandNational Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Khlong Nueng, Khlong Luang, Pathum Thani 12120, ThailandNational Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Khlong Nueng, Khlong Luang, Pathum Thani 12120, ThailandBackground: Middle East Respiratory Syndrome Coronavirus (MERS-CoV) causes severe respiratory illness in humans and currently lacks an approved vaccine. The Newcastle disease virus (NDV) vector is a well-established, safe, and effective platform for vaccine development. With recent advancements in stabilizing coronavirus spike proteins to enhance their antigenicity, this study aimed to determine whether modifications to the MERS-CoV spike protein could improve its presentation on NDV particles, allowing the resulting virus to be used as an inactivated vaccine. Methods: We codon-optimized the gene encoding the ectodomain of the MERS-CoV spike protein and incorporated modifications at the S1/S2 and S2’ cleavage sites, along with a proline substitution at residues V1060-L1061. This modified spike gene was inserted into the NDV genome to create the NDV-S<sub>MERS</sub> virus. After purification and inactivation, the vaccine’s immunogenicity was assessed in mice. Results: Mice immunized with the inactivated NDV-S<sub>MERS</sub> vaccine developed robust anti-spike IgGs, neutralizing antibodies, and cellular immune responses. The study demonstrated that modifications to the MERS-CoV spike protein were essential for its effective presentation on NDV particles. Additionally, the spike gene insert remained stable through five egg passages, confirming the vector’s stability. Conclusions: Engineering the MERS-CoV spike protein is crucial for its successful display on NDV particles. The strong immune responses elicited by the NDV-S<sub>MERS</sub> vaccine in mice highlight that NDV is a promising, safe, and effective platform for MERS-CoV vaccination.https://www.mdpi.com/2076-393X/13/1/2Newcastle disease virusMERS-CoVvaccinespikeneutralizing antibodymouse model
spellingShingle Jaturawitt Prasopsiri
Kanjana Srisutthisamphan
Benjamas Liwnaree
Juggragarn Jengarn
Jarin Kramyu
Payuda Hansoongnern
Papon Muangsanit
Nathiphat Tanwattana
Challika Kaewborisuth
Suttipun Sungsuwan
Anan Jongkaewwattana
Nanchaya Wanasen
Newcastle Disease Virus Displaying an Ectodomain of Middle East Respiratory Syndrome Coronavirus Spike Protein Elicited Robust Humoral and Cellular Immunity in Mice
Vaccines
Newcastle disease virus
MERS-CoV
vaccine
spike
neutralizing antibody
mouse model
title Newcastle Disease Virus Displaying an Ectodomain of Middle East Respiratory Syndrome Coronavirus Spike Protein Elicited Robust Humoral and Cellular Immunity in Mice
title_full Newcastle Disease Virus Displaying an Ectodomain of Middle East Respiratory Syndrome Coronavirus Spike Protein Elicited Robust Humoral and Cellular Immunity in Mice
title_fullStr Newcastle Disease Virus Displaying an Ectodomain of Middle East Respiratory Syndrome Coronavirus Spike Protein Elicited Robust Humoral and Cellular Immunity in Mice
title_full_unstemmed Newcastle Disease Virus Displaying an Ectodomain of Middle East Respiratory Syndrome Coronavirus Spike Protein Elicited Robust Humoral and Cellular Immunity in Mice
title_short Newcastle Disease Virus Displaying an Ectodomain of Middle East Respiratory Syndrome Coronavirus Spike Protein Elicited Robust Humoral and Cellular Immunity in Mice
title_sort newcastle disease virus displaying an ectodomain of middle east respiratory syndrome coronavirus spike protein elicited robust humoral and cellular immunity in mice
topic Newcastle disease virus
MERS-CoV
vaccine
spike
neutralizing antibody
mouse model
url https://www.mdpi.com/2076-393X/13/1/2
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