Strategies for Enhancement of Live-Attenuated <i>Salmonella</i>-Based Carrier Vaccine Immunogenicity
The use of live-attenuated bacterial vaccines as carriers for the mucosal delivery of foreign antigens to stimulate the mucosal immune system was first proposed over three decades ago. This novel strategy aimed to induce immunity against at least two distinct pathogens using a single bivalent carrie...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-02-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/9/2/162 |
| _version_ | 1827589107051659264 |
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| author | James E. Galen Rezwanul Wahid Amanda D. Buskirk |
| author_facet | James E. Galen Rezwanul Wahid Amanda D. Buskirk |
| author_sort | James E. Galen |
| collection | DOAJ |
| description | The use of live-attenuated bacterial vaccines as carriers for the mucosal delivery of foreign antigens to stimulate the mucosal immune system was first proposed over three decades ago. This novel strategy aimed to induce immunity against at least two distinct pathogens using a single bivalent carrier vaccine. It was first tested using a live-attenuated <i>Salmonella enterica</i> serovar Typhi strain in clinical trials in 1984, with excellent humoral immune responses against the carrier strain but only modest responses elicited against the foreign antigen. Since then, clinical trials with additional <i>Salmonella</i>-based carrier vaccines have been conducted. As with the original trial, only modest foreign antigen-specific immunity was achieved in most cases, despite the incorporation of incremental improvements in antigen expression technologies and carrier design over the years. In this review, we will attempt to deconstruct carrier vaccine immunogenicity in humans by examining the basis of bacterial immunity in the human gastrointestinal tract and how the gut detects and responds to pathogens versus benign commensal organisms. Carrier vaccine design will then be explored to determine the feasibility of retaining as many characteristics of a pathogen as possible to elicit robust carrier and foreign antigen-specific immunity, while avoiding over-stimulation of unacceptably reactogenic inflammatory responses. |
| first_indexed | 2024-03-09T00:49:58Z |
| format | Article |
| id | doaj.art-d6c363ce6df244a19a0cc22d7c6e35fa |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-09T00:49:58Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-d6c363ce6df244a19a0cc22d7c6e35fa2023-12-11T17:19:14ZengMDPI AGVaccines2076-393X2021-02-019216210.3390/vaccines9020162Strategies for Enhancement of Live-Attenuated <i>Salmonella</i>-Based Carrier Vaccine ImmunogenicityJames E. Galen0Rezwanul Wahid1Amanda D. Buskirk2Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD 21201, USACenter for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD 21201, USACenter for Drug Evaluation and Research, Office of Pharmaceutical Quality, Office of Process and Facilities, Division of Microbiology Assessment II, U.S. Food and Drug Administration, Silver Spring, MD 20903, USAThe use of live-attenuated bacterial vaccines as carriers for the mucosal delivery of foreign antigens to stimulate the mucosal immune system was first proposed over three decades ago. This novel strategy aimed to induce immunity against at least two distinct pathogens using a single bivalent carrier vaccine. It was first tested using a live-attenuated <i>Salmonella enterica</i> serovar Typhi strain in clinical trials in 1984, with excellent humoral immune responses against the carrier strain but only modest responses elicited against the foreign antigen. Since then, clinical trials with additional <i>Salmonella</i>-based carrier vaccines have been conducted. As with the original trial, only modest foreign antigen-specific immunity was achieved in most cases, despite the incorporation of incremental improvements in antigen expression technologies and carrier design over the years. In this review, we will attempt to deconstruct carrier vaccine immunogenicity in humans by examining the basis of bacterial immunity in the human gastrointestinal tract and how the gut detects and responds to pathogens versus benign commensal organisms. Carrier vaccine design will then be explored to determine the feasibility of retaining as many characteristics of a pathogen as possible to elicit robust carrier and foreign antigen-specific immunity, while avoiding over-stimulation of unacceptably reactogenic inflammatory responses.https://www.mdpi.com/2076-393X/9/2/162SalmonellaTyphicarrier vaccineimmunogenicityhomeostasisinflammation |
| spellingShingle | James E. Galen Rezwanul Wahid Amanda D. Buskirk Strategies for Enhancement of Live-Attenuated <i>Salmonella</i>-Based Carrier Vaccine Immunogenicity Vaccines Salmonella Typhi carrier vaccine immunogenicity homeostasis inflammation |
| title | Strategies for Enhancement of Live-Attenuated <i>Salmonella</i>-Based Carrier Vaccine Immunogenicity |
| title_full | Strategies for Enhancement of Live-Attenuated <i>Salmonella</i>-Based Carrier Vaccine Immunogenicity |
| title_fullStr | Strategies for Enhancement of Live-Attenuated <i>Salmonella</i>-Based Carrier Vaccine Immunogenicity |
| title_full_unstemmed | Strategies for Enhancement of Live-Attenuated <i>Salmonella</i>-Based Carrier Vaccine Immunogenicity |
| title_short | Strategies for Enhancement of Live-Attenuated <i>Salmonella</i>-Based Carrier Vaccine Immunogenicity |
| title_sort | strategies for enhancement of live attenuated i salmonella i based carrier vaccine immunogenicity |
| topic | Salmonella Typhi carrier vaccine immunogenicity homeostasis inflammation |
| url | https://www.mdpi.com/2076-393X/9/2/162 |
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