A Virus-like Particle-Based F4 Enterotoxigenic <i>Escherichia coli</i> Vaccine Is Inhibited by Maternally Derived Antibodies in Piglets but Generates Robust Responses in Sows
F4-positive enterotoxigenic <i>Escherichia coli</i> is associated with diarrhea and poor growth outcomes in neonatal and newly weaned piglets and is thus a major economic and welfare burden in the swine industry. Vaccination of sows with F4 fimbriae protects against the neonatal disease...
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MDPI AG
2023-11-01
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| Series: | Pathogens |
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| Online Access: | https://www.mdpi.com/2076-0817/12/12/1388 |
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| author | Kara-Lee Aves Priscila R. Guerra Ana H. Fresno Mauro M. S. Saraiva Eric Cox Poul J. Bækbo Morten A. Nielsen Adam F. Sander John E. Olsen |
| author_facet | Kara-Lee Aves Priscila R. Guerra Ana H. Fresno Mauro M. S. Saraiva Eric Cox Poul J. Bækbo Morten A. Nielsen Adam F. Sander John E. Olsen |
| author_sort | Kara-Lee Aves |
| collection | DOAJ |
| description | F4-positive enterotoxigenic <i>Escherichia coli</i> is associated with diarrhea and poor growth outcomes in neonatal and newly weaned piglets and is thus a major economic and welfare burden in the swine industry. Vaccination of sows with F4 fimbriae protects against the neonatal disease via passive transfer of maternal immunity. However, this strategy does not protect against infection post-weaning. Consequently, prevention and treatment methods in weaner pigs heavily rely on the use of antimicrobials. Therefore, in order to reduce antimicrobial consumption, more effective prophylactic alternatives are needed. In this study, we describe the development of a capsid virus-like particle (cVLP)-based vaccine targeting the major F4 fimbriae subunit and adhesion molecule, FaeG, and evaluate its immunogenicity in mice, piglets, and sows. cVLP-display significantly increased systemic and mucosal antibody responses towards the recombinant FaeG antigen in mice models. However, in piglets, the presence of anti-F4 maternally derived antibodies severely inhibited the induction of active humoral responses towards the FaeG antigen. This inhibition could not be overcome, even with the enhanced immunogenicity achieved via cVLP display. However, in sows, intramuscular vaccination with the FaeG.cVLP vaccine was able to generate robust IgG and IgA responses that were comparable with a commercial fimbriae-based vaccine, and which were effectively transferred to piglets via colostrum intake. These results demonstrate that cVLP display has the potential to improve the systemic humoral responses elicited against low-immunogenic antigens in pigs; however, this effect is dependent on the use of antigens, which are not the targets of pre-existing maternal immunity. |
| first_indexed | 2024-03-08T20:28:33Z |
| format | Article |
| id | doaj.art-f415a7e958574ed0af94ad5f4c3cdf5c |
| institution | Directory Open Access Journal |
| issn | 2076-0817 |
| language | English |
| last_indexed | 2024-03-08T20:28:33Z |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pathogens |
| spelling | doaj.art-f415a7e958574ed0af94ad5f4c3cdf5c2023-12-22T14:30:47ZengMDPI AGPathogens2076-08172023-11-011212138810.3390/pathogens12121388A Virus-like Particle-Based F4 Enterotoxigenic <i>Escherichia coli</i> Vaccine Is Inhibited by Maternally Derived Antibodies in Piglets but Generates Robust Responses in SowsKara-Lee Aves0Priscila R. Guerra1Ana H. Fresno2Mauro M. S. Saraiva3Eric Cox4Poul J. Bækbo5Morten A. Nielsen6Adam F. Sander7John E. Olsen8Department of Immunology and Microbiology, University of Copenhagen, DK-2200 Copenhagen, DenmarkDepartment of Veterinary and Animal Sciences, University of Copenhagen, DK-1870 Frederiksberg, DenmarkDepartment of Veterinary and Animal Sciences, University of Copenhagen, DK-1870 Frederiksberg, DenmarkDepartment of Veterinary and Animal Sciences, University of Copenhagen, DK-1870 Frederiksberg, DenmarkLaboratory of Immunology, Faculty of Veterinary Medicine, Ghent University, B-9820 Merelbeke, BelgiumSEGES Innovation, Danish Pig Research Centre, Agro Food Park 15, DK-8200 Aarhus, DenmarkDepartment of Immunology and Microbiology, University of Copenhagen, DK-2200 Copenhagen, DenmarkDepartment of Immunology and Microbiology, University of Copenhagen, DK-2200 Copenhagen, DenmarkDepartment of Veterinary and Animal Sciences, University of Copenhagen, DK-1870 Frederiksberg, DenmarkF4-positive enterotoxigenic <i>Escherichia coli</i> is associated with diarrhea and poor growth outcomes in neonatal and newly weaned piglets and is thus a major economic and welfare burden in the swine industry. Vaccination of sows with F4 fimbriae protects against the neonatal disease via passive transfer of maternal immunity. However, this strategy does not protect against infection post-weaning. Consequently, prevention and treatment methods in weaner pigs heavily rely on the use of antimicrobials. Therefore, in order to reduce antimicrobial consumption, more effective prophylactic alternatives are needed. In this study, we describe the development of a capsid virus-like particle (cVLP)-based vaccine targeting the major F4 fimbriae subunit and adhesion molecule, FaeG, and evaluate its immunogenicity in mice, piglets, and sows. cVLP-display significantly increased systemic and mucosal antibody responses towards the recombinant FaeG antigen in mice models. However, in piglets, the presence of anti-F4 maternally derived antibodies severely inhibited the induction of active humoral responses towards the FaeG antigen. This inhibition could not be overcome, even with the enhanced immunogenicity achieved via cVLP display. However, in sows, intramuscular vaccination with the FaeG.cVLP vaccine was able to generate robust IgG and IgA responses that were comparable with a commercial fimbriae-based vaccine, and which were effectively transferred to piglets via colostrum intake. These results demonstrate that cVLP display has the potential to improve the systemic humoral responses elicited against low-immunogenic antigens in pigs; however, this effect is dependent on the use of antigens, which are not the targets of pre-existing maternal immunity.https://www.mdpi.com/2076-0817/12/12/1388F4+ enterotoxigenic <i>E. coli</i>post-weaning diarrheavirus-like particleFaeGStb toxinmaternal antibody inhibition |
| spellingShingle | Kara-Lee Aves Priscila R. Guerra Ana H. Fresno Mauro M. S. Saraiva Eric Cox Poul J. Bækbo Morten A. Nielsen Adam F. Sander John E. Olsen A Virus-like Particle-Based F4 Enterotoxigenic <i>Escherichia coli</i> Vaccine Is Inhibited by Maternally Derived Antibodies in Piglets but Generates Robust Responses in Sows Pathogens F4+ enterotoxigenic <i>E. coli</i> post-weaning diarrhea virus-like particle FaeG Stb toxin maternal antibody inhibition |
| title | A Virus-like Particle-Based F4 Enterotoxigenic <i>Escherichia coli</i> Vaccine Is Inhibited by Maternally Derived Antibodies in Piglets but Generates Robust Responses in Sows |
| title_full | A Virus-like Particle-Based F4 Enterotoxigenic <i>Escherichia coli</i> Vaccine Is Inhibited by Maternally Derived Antibodies in Piglets but Generates Robust Responses in Sows |
| title_fullStr | A Virus-like Particle-Based F4 Enterotoxigenic <i>Escherichia coli</i> Vaccine Is Inhibited by Maternally Derived Antibodies in Piglets but Generates Robust Responses in Sows |
| title_full_unstemmed | A Virus-like Particle-Based F4 Enterotoxigenic <i>Escherichia coli</i> Vaccine Is Inhibited by Maternally Derived Antibodies in Piglets but Generates Robust Responses in Sows |
| title_short | A Virus-like Particle-Based F4 Enterotoxigenic <i>Escherichia coli</i> Vaccine Is Inhibited by Maternally Derived Antibodies in Piglets but Generates Robust Responses in Sows |
| title_sort | virus like particle based f4 enterotoxigenic i escherichia coli i vaccine is inhibited by maternally derived antibodies in piglets but generates robust responses in sows |
| topic | F4+ enterotoxigenic <i>E. coli</i> post-weaning diarrhea virus-like particle FaeG Stb toxin maternal antibody inhibition |
| url | https://www.mdpi.com/2076-0817/12/12/1388 |
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