A Lactic Acid Bacteria (LAB)-Based Vaccine Candidate for Human Norovirus
Human noroviruses (HuNoVs) are responsible for more than 95% of the non-bacterial acute gastroenteritis epidemics in the world. The CDC estimates that every year 21 million individuals suffer from HuNoV-induced gastroenteritis in the United States. Currently, there is no FDA-approved vaccine for HuN...
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| Format: | Article |
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MDPI AG
2019-03-01
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| Series: | Viruses |
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| Online Access: | http://www.mdpi.com/1999-4915/11/3/213 |
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| author | Kelsey Craig Xianjun Dai Anzhong Li Mijia Lu Miaoge Xue Lucia Rosas Thomas Z. Gao Andrew Niehaus Ryan Jennings Jianrong Li |
| author_facet | Kelsey Craig Xianjun Dai Anzhong Li Mijia Lu Miaoge Xue Lucia Rosas Thomas Z. Gao Andrew Niehaus Ryan Jennings Jianrong Li |
| author_sort | Kelsey Craig |
| collection | DOAJ |
| description | Human noroviruses (HuNoVs) are responsible for more than 95% of the non-bacterial acute gastroenteritis epidemics in the world. The CDC estimates that every year 21 million individuals suffer from HuNoV-induced gastroenteritis in the United States. Currently, there is no FDA-approved vaccine for HuNoVs. Development of an effective vaccine has been hampered by the lack of an efficient cell culture system for HuNoVs and a suitable small animal model for pathogenesis study. In this study, we developed lactic acid bacteria (LAB) as a vector to deliver HuNoV antigen. A LAB strain (Lactococcus lactis) carrying VP1 gene of a HuNoV GII.4 virus (LAB-VP1) was constructed. It was found that HuNoV VP1 protein was highly expressed by LAB vector and was secreted into media supernatants. To test whether LAB-based HuNoV vaccine candidate is immunogenic, 4-day-old gnotobiotic piglets were orally inoculated with various doses of LAB-VP1. It was found that LABs were persistent in the small intestine of piglets and shed in pig feces for at least 25 days post inoculation. LAB DNA and VP1 were detected in mesenteric lymph nodes and spleen tissue in LAB-VP1 inoculated groups. HuNoV-specific IgG and IgA were detectable in serum and feces respectively at day 13 post-inoculation, and further increased at later time points. After being challenged with HuNoV GII.4 strain, a large amount of HuNoV antigens were observed in the duodenum, jejunum, and ileum sections of the intestine in the LAB control group. In contrast, significantly less, or no, HuNoV antigens were detected in the LAB-VP1 immunized groups. Collectively, these results demonstrate that a LAB-based HuNoV vaccine induces protective immunity in gnotobiotic piglets. |
| first_indexed | 2024-12-23T13:54:14Z |
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| id | doaj.art-985af390ea8945028927488c5db11033 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-12-23T13:54:14Z |
| publishDate | 2019-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-985af390ea8945028927488c5db110332022-12-21T17:44:31ZengMDPI AGViruses1999-49152019-03-0111321310.3390/v11030213v11030213A Lactic Acid Bacteria (LAB)-Based Vaccine Candidate for Human NorovirusKelsey Craig0Xianjun Dai1Anzhong Li2Mijia Lu3Miaoge Xue4Lucia Rosas5Thomas Z. Gao6Andrew Niehaus7Ryan Jennings8Jianrong Li9Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USADepartment of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USADepartment of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USADepartment of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USADepartment of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USADepartment of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USADepartment of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USADepartment of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USADepartment of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USADepartment of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USAHuman noroviruses (HuNoVs) are responsible for more than 95% of the non-bacterial acute gastroenteritis epidemics in the world. The CDC estimates that every year 21 million individuals suffer from HuNoV-induced gastroenteritis in the United States. Currently, there is no FDA-approved vaccine for HuNoVs. Development of an effective vaccine has been hampered by the lack of an efficient cell culture system for HuNoVs and a suitable small animal model for pathogenesis study. In this study, we developed lactic acid bacteria (LAB) as a vector to deliver HuNoV antigen. A LAB strain (Lactococcus lactis) carrying VP1 gene of a HuNoV GII.4 virus (LAB-VP1) was constructed. It was found that HuNoV VP1 protein was highly expressed by LAB vector and was secreted into media supernatants. To test whether LAB-based HuNoV vaccine candidate is immunogenic, 4-day-old gnotobiotic piglets were orally inoculated with various doses of LAB-VP1. It was found that LABs were persistent in the small intestine of piglets and shed in pig feces for at least 25 days post inoculation. LAB DNA and VP1 were detected in mesenteric lymph nodes and spleen tissue in LAB-VP1 inoculated groups. HuNoV-specific IgG and IgA were detectable in serum and feces respectively at day 13 post-inoculation, and further increased at later time points. After being challenged with HuNoV GII.4 strain, a large amount of HuNoV antigens were observed in the duodenum, jejunum, and ileum sections of the intestine in the LAB control group. In contrast, significantly less, or no, HuNoV antigens were detected in the LAB-VP1 immunized groups. Collectively, these results demonstrate that a LAB-based HuNoV vaccine induces protective immunity in gnotobiotic piglets.http://www.mdpi.com/1999-4915/11/3/213human noroviruslactic acid bacteriagnotobiotic pigletvaccineVP1 |
| spellingShingle | Kelsey Craig Xianjun Dai Anzhong Li Mijia Lu Miaoge Xue Lucia Rosas Thomas Z. Gao Andrew Niehaus Ryan Jennings Jianrong Li A Lactic Acid Bacteria (LAB)-Based Vaccine Candidate for Human Norovirus Viruses human norovirus lactic acid bacteria gnotobiotic piglet vaccine VP1 |
| title | A Lactic Acid Bacteria (LAB)-Based Vaccine Candidate for Human Norovirus |
| title_full | A Lactic Acid Bacteria (LAB)-Based Vaccine Candidate for Human Norovirus |
| title_fullStr | A Lactic Acid Bacteria (LAB)-Based Vaccine Candidate for Human Norovirus |
| title_full_unstemmed | A Lactic Acid Bacteria (LAB)-Based Vaccine Candidate for Human Norovirus |
| title_short | A Lactic Acid Bacteria (LAB)-Based Vaccine Candidate for Human Norovirus |
| title_sort | lactic acid bacteria lab based vaccine candidate for human norovirus |
| topic | human norovirus lactic acid bacteria gnotobiotic piglet vaccine VP1 |
| url | http://www.mdpi.com/1999-4915/11/3/213 |
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