MersV1, Main, Exploration, bibRecord, 000609

Effect of Fc Fusion on Folding and Immunogenicity of Middle East Respiratory Syndrome Coronavirus Spike Protein.

Identifieur interne : 000609 ( Main/Exploration ); précédent : 000608; suivant : 000610

Effect of Fc Fusion on Folding and Immunogenicity of Middle East Respiratory Syndrome Coronavirus Spike Protein.

Auteurs : Jungmin Chun [Corée du Sud] ; Yeondong Cho [Corée du Sud] ; Ki Hoon Park [Corée du Sud] ; Hanul Choi [Corée du Sud] ; Hansam Cho [Corée du Sud] ; Hee-Jung Lee [Corée du Sud] ; Hyun Jang [Corée du Sud] ; Kyung Hyun Kim [Corée du Sud] ; Yu-Kyoung Oh [Corée du Sud] ; Young Bong Kim [Corée du Sud]

Source :

Journal of microbiology and biotechnology [ 1738-8872 ] ; 2019.

RBID : pubmed:30982320

Descripteurs français

English descriptors

KwdEn :
- Animals, Antibodies, Neutralizing, Antibodies, Viral, Antigens, Viral (genetics), Coronavirus Infections (prevention & control), Female, Immunization, Immunogenicity, Vaccine, Immunoglobulin Fc Fragments (immunology), Immunoglobulin G, Mice, Mice, Inbred BALB C, Middle East Respiratory Syndrome Coronavirus (genetics), Middle East Respiratory Syndrome Coronavirus (immunology), Middle East Respiratory Syndrome Coronavirus (pathogenicity), Neutralization Tests, Protein Folding, Recombinant Fusion Proteins (immunology), Sf9 Cells, Spike Glycoprotein, Coronavirus (chemistry), Spike Glycoprotein, Coronavirus (genetics), Spike Glycoprotein, Coronavirus (immunology), Vaccination, Vaccines, Subunit (immunology), Viral Vaccines (genetics), Viral Vaccines (immunology).
MESH :
- chemical , chemistry : Spike Glycoprotein, Coronavirus.
- chemical , genetics : Antigens, Viral, Spike Glycoprotein, Coronavirus, Viral Vaccines.
- chemical , immunology : Immunoglobulin Fc Fragments, Recombinant Fusion Proteins, Spike Glycoprotein, Coronavirus, Vaccines, Subunit, Viral Vaccines.
- chemical : Antibodies, Neutralizing, Antibodies, Viral, Immunoglobulin G.
- genetics : Middle East Respiratory Syndrome Coronavirus.
- immunology : Middle East Respiratory Syndrome Coronavirus.
- pathogenicity : Middle East Respiratory Syndrome Coronavirus.
- prevention & control : Coronavirus Infections.
- Animals, Female, Immunization, Immunogenicity, Vaccine, Mice, Mice, Inbred BALB C, Neutralization Tests, Protein Folding, Sf9 Cells, Vaccination.

Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) induces severe respiratory impairment with a reported mortality rate of ~36% in humans. The absence of clinically available MERS-CoV vaccines and treatments to date has resulted in uncontrolled incidence and propagation of the virus. In vaccine design, fusion with the IgG Fc domain is reported to increase the immunogenicity of various vaccine antigens. However, limited reports have documented the potential negative effects of Fc fusion on vaccine antigens. To determine whether Fc fusion affects the immunogenicity of MERS-CoV antigen, we constructed a Fcassociated MERS-CoV spike protein (eS770-Fc, 110 kDa), whereby human IgG4 Fc domain was fused to MERS-CoV spike protein (eS770) via a Gly/Pro linker using baculovirus as the expression system. For comparative analyses, two eS770 proteins lacking the IgG4 Fc domain were generated using the IdeS protease (eS770-ΔFc) or His tag attachment (eS770-His) and the immunogenicity of the above constructs were examined following intramuscular immunization in mice. Contrary to expectations, non-Fc spike proteins (eS770-ΔFc, eS770-His; 90 kDa) showed higher immunogenicity than the Fc fusion protein (eS770-Fc). Moreover, unlike non- Fc spike proteins, eS770-Fc immunization did not elicit neutralizing antibodies against MERSCoV. The lower immunogenicity of Fc-fused eS770 was related to alterations in the structural conformation of the spike protein. Taken together, our results indicate that IgG Fc fusion reduces the immunogenicity of eS770 by interfering with the proper folding structure.

DOI: 10.4014/jmb.1903.03043
PubMed: 30982320

Affiliations:

Le document en format XML

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<front><div type="abstract" xml:lang="en">Middle East respiratory syndrome coronavirus (MERS-CoV) induces severe respiratory impairment with a reported mortality rate of ~36% in humans. The absence of clinically available MERS-CoV vaccines and treatments to date has resulted in uncontrolled incidence and propagation of the virus. In vaccine design, fusion with the IgG Fc domain is reported to increase the immunogenicity of various vaccine antigens. However, limited reports have documented the potential negative effects of Fc fusion on vaccine antigens. To determine whether Fc fusion affects the immunogenicity of MERS-CoV antigen, we constructed a Fcassociated MERS-CoV spike protein (eS770-Fc, 110 kDa), whereby human IgG4 Fc domain was fused to MERS-CoV spike protein (eS770) via a Gly/Pro linker using baculovirus as the expression system. For comparative analyses, two eS770 proteins lacking the IgG4 Fc domain were generated using the IdeS protease (eS770-ΔFc) or His tag attachment (eS770-His) and the immunogenicity of the above constructs were examined following intramuscular immunization in mice. Contrary to expectations, non-Fc spike proteins (eS770-ΔFc, eS770-His; 90 kDa) showed higher immunogenicity than the Fc fusion protein (eS770-Fc). Moreover, unlike non- Fc spike proteins, eS770-Fc immunization did not elicit neutralizing antibodies against MERSCoV. The lower immunogenicity of Fc-fused eS770 was related to alterations in the structural conformation of the spike protein. Taken together, our results indicate that IgG Fc fusion reduces the immunogenicity of eS770 by interfering with the proper folding structure.</div>
</front>
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</region>
<name sortKey="Cho, Hansam" sort="Cho, Hansam" uniqKey="Cho H" first="Hansam" last="Cho">Hansam Cho</name>
<name sortKey="Cho, Yeondong" sort="Cho, Yeondong" uniqKey="Cho Y" first="Yeondong" last="Cho">Yeondong Cho</name>
<name sortKey="Choi, Hanul" sort="Choi, Hanul" uniqKey="Choi H" first="Hanul" last="Choi">Hanul Choi</name>
<name sortKey="Jang, Hyun" sort="Jang, Hyun" uniqKey="Jang H" first="Hyun" last="Jang">Hyun Jang</name>
<name sortKey="Kim, Kyung Hyun" sort="Kim, Kyung Hyun" uniqKey="Kim K" first="Kyung Hyun" last="Kim">Kyung Hyun Kim</name>
<name sortKey="Kim, Young Bong" sort="Kim, Young Bong" uniqKey="Kim Y" first="Young Bong" last="Kim">Young Bong Kim</name>
<name sortKey="Lee, Hee Jung" sort="Lee, Hee Jung" uniqKey="Lee H" first="Hee-Jung" last="Lee">Hee-Jung Lee</name>
<name sortKey="Oh, Yu Kyoung" sort="Oh, Yu Kyoung" uniqKey="Oh Y" first="Yu-Kyoung" last="Oh">Yu-Kyoung Oh</name>
<name sortKey="Park, Ki Hoon" sort="Park, Ki Hoon" uniqKey="Park K" first="Ki Hoon" last="Park">Ki Hoon Park</name>
</country>
</tree>
</affiliations>
</record>

Pour manipuler ce document sous Unix (Dilib)

EXPLOR_STEP=$WICRI_ROOT/Sante/explor/MersV1/Data/Main/Exploration

HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000609 | SxmlIndent | more

HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 000609 | SxmlIndent | more

Pour mettre un lien sur cette page dans le réseau Wicri

{{Explor lien
   |wiki=    Sante
   |area=    MersV1
   |flux=    Main
   |étape=   Exploration
   |type=    RBID
   |clé=     pubmed:30982320
   |texte=   Effect of Fc Fusion on Folding and Immunogenicity of Middle East Respiratory Syndrome Coronavirus Spike Protein.
}}

Pour générer des pages wiki

HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i   -Sk "pubmed:30982320" \
       | HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd   \
       | NlmPubMed2Wicri -a MersV1

This area was generated with Dilib version V0.6.33.
Data generation: Mon Apr 20 23:26:43 2020. Site generation: Sat Mar 27 09:06:09 2021

Serveur d'exploration MERS

Effect of Fc Fusion on Folding and Immunogenicity of Middle East Respiratory Syndrome Coronavirus Spike Protein.

Effect of Fc Fusion on Folding and Immunogenicity of Middle East Respiratory Syndrome Coronavirus Spike Protein.

Source :

Descripteurs français

English descriptors

Abstract

Links toward previous steps (curation, corpus...)

Le document en format XML

Pour manipuler ce document sous Unix (Dilib)

Pour mettre un lien sur cette page dans le réseau Wicri

Pour générer des pages wiki

	Serveur d'exploration MERS
	Attention, ce site est en cours de développement ! Attention, site généré par des moyens informatiques à partir de corpus bruts. Les informations ne sont donc pas validées.