Oral Delivery of Novel Recombinant <i>Lactobacillus</i> Elicit High Protection against <i>Staphylococcus aureus</i> Pulmonary and Skin Infections
<i>Staphylococcus aureus</i> is a leading cause of nosocomial and community-associated infection worldwide; however, there is no licensed vaccine available. <i>S. aureus</i> initiates infection via the mucosa; therefore, a mucosal vaccine is likely to be a promising approach...
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| Format: | Article |
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MDPI AG
2021-09-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/9/9/984 |
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| author | Na Pan Bohui Liu Xuemei Bao Haochi Zhang Shouxin Sheng Yanchen Liang Haiting Pan Xiao Wang |
| author_facet | Na Pan Bohui Liu Xuemei Bao Haochi Zhang Shouxin Sheng Yanchen Liang Haiting Pan Xiao Wang |
| author_sort | Na Pan |
| collection | DOAJ |
| description | <i>Staphylococcus aureus</i> is a leading cause of nosocomial and community-associated infection worldwide; however, there is no licensed vaccine available. <i>S. aureus</i> initiates infection via the mucosa; therefore, a mucosal vaccine is likely to be a promising approach against <i>S. aureus</i> infection. Lactobacilli, a non-pathogenic bacterium, has gained increasing interest as a mucosal delivery vehicle. Hence, we attempted to develop an oral <i>S. aureus</i> vaccine based on lactobacilli to cushion the stress of drug resistance and vaccine needs. In this study, we designed, constructed, and evaluated recombinant <i>Lactobacillus</i> strains synthesizing <i>S. aureus</i> nontoxic mutated α-hemolysins (Hla<sub>H35L</sub>). The results from animal clinical trials showed that recombinant <i>Lactobacillus</i> can persist for at least 72 h and can stably express heterologous protein in vivo. Recombinant <i>L. plantarum</i> WXD234 (pNZ8148-Hla) could induce robust mucosal immunity in the GALT, as evidenced by a significant increase in IgA and IL-17 production and the strong proliferation of T-lymphocytes derived from Peyer’s patches. WXD234 (pNZ8148-Hla) conferred up to 83% protection against <i>S. aureus</i> pulmonary infection and significantly reduced the abscess size in a <i>S. aureus</i> skin infection model. Of particular interest is the sharp reduction of the protective effect offered by WXD234 (pNZ8148-Hla) vaccination in γδ T cell-deficient or IL-17-deficient mice. In conclusion, for the first time, genetically engineered <i>Lactobacillus</i> WXD234 (pNZ8148-Hla) as an oral vaccine induced superior mucosal immunity, which was associated with high protection against pulmonary and skin infections caused by <i>S. aureus</i>. Taken together, our findings suggest the great potential for a delivery system based on lactobacilli and provide experimental data for the development of mucosal vaccines for <i>S. aureus</i>. |
| first_indexed | 2024-03-10T07:08:49Z |
| format | Article |
| id | doaj.art-9192e66485114310a614d9a568c5cf15 |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-10T07:08:49Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-9192e66485114310a614d9a568c5cf152023-11-22T15:34:26ZengMDPI AGVaccines2076-393X2021-09-019998410.3390/vaccines9090984Oral Delivery of Novel Recombinant <i>Lactobacillus</i> Elicit High Protection against <i>Staphylococcus aureus</i> Pulmonary and Skin InfectionsNa Pan0Bohui Liu1Xuemei Bao2Haochi Zhang3Shouxin Sheng4Yanchen Liang5Haiting Pan6Xiao Wang7State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, Inner Mongolia University, Hohhot 010070, ChinaState Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, Inner Mongolia University, Hohhot 010070, ChinaState Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, Inner Mongolia University, Hohhot 010070, ChinaState Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, Inner Mongolia University, Hohhot 010070, ChinaState Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, Inner Mongolia University, Hohhot 010070, ChinaState Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, Inner Mongolia University, Hohhot 010070, ChinaState Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, Inner Mongolia University, Hohhot 010070, ChinaState Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, Inner Mongolia University, Hohhot 010070, China<i>Staphylococcus aureus</i> is a leading cause of nosocomial and community-associated infection worldwide; however, there is no licensed vaccine available. <i>S. aureus</i> initiates infection via the mucosa; therefore, a mucosal vaccine is likely to be a promising approach against <i>S. aureus</i> infection. Lactobacilli, a non-pathogenic bacterium, has gained increasing interest as a mucosal delivery vehicle. Hence, we attempted to develop an oral <i>S. aureus</i> vaccine based on lactobacilli to cushion the stress of drug resistance and vaccine needs. In this study, we designed, constructed, and evaluated recombinant <i>Lactobacillus</i> strains synthesizing <i>S. aureus</i> nontoxic mutated α-hemolysins (Hla<sub>H35L</sub>). The results from animal clinical trials showed that recombinant <i>Lactobacillus</i> can persist for at least 72 h and can stably express heterologous protein in vivo. Recombinant <i>L. plantarum</i> WXD234 (pNZ8148-Hla) could induce robust mucosal immunity in the GALT, as evidenced by a significant increase in IgA and IL-17 production and the strong proliferation of T-lymphocytes derived from Peyer’s patches. WXD234 (pNZ8148-Hla) conferred up to 83% protection against <i>S. aureus</i> pulmonary infection and significantly reduced the abscess size in a <i>S. aureus</i> skin infection model. Of particular interest is the sharp reduction of the protective effect offered by WXD234 (pNZ8148-Hla) vaccination in γδ T cell-deficient or IL-17-deficient mice. In conclusion, for the first time, genetically engineered <i>Lactobacillus</i> WXD234 (pNZ8148-Hla) as an oral vaccine induced superior mucosal immunity, which was associated with high protection against pulmonary and skin infections caused by <i>S. aureus</i>. Taken together, our findings suggest the great potential for a delivery system based on lactobacilli and provide experimental data for the development of mucosal vaccines for <i>S. aureus</i>.https://www.mdpi.com/2076-393X/9/9/984<i>Staphylococcus aureus</i>oral vaccine<i>Lactobacillus</i>mucosal delivery |
| spellingShingle | Na Pan Bohui Liu Xuemei Bao Haochi Zhang Shouxin Sheng Yanchen Liang Haiting Pan Xiao Wang Oral Delivery of Novel Recombinant <i>Lactobacillus</i> Elicit High Protection against <i>Staphylococcus aureus</i> Pulmonary and Skin Infections Vaccines <i>Staphylococcus aureus</i> oral vaccine <i>Lactobacillus</i> mucosal delivery |
| title | Oral Delivery of Novel Recombinant <i>Lactobacillus</i> Elicit High Protection against <i>Staphylococcus aureus</i> Pulmonary and Skin Infections |
| title_full | Oral Delivery of Novel Recombinant <i>Lactobacillus</i> Elicit High Protection against <i>Staphylococcus aureus</i> Pulmonary and Skin Infections |
| title_fullStr | Oral Delivery of Novel Recombinant <i>Lactobacillus</i> Elicit High Protection against <i>Staphylococcus aureus</i> Pulmonary and Skin Infections |
| title_full_unstemmed | Oral Delivery of Novel Recombinant <i>Lactobacillus</i> Elicit High Protection against <i>Staphylococcus aureus</i> Pulmonary and Skin Infections |
| title_short | Oral Delivery of Novel Recombinant <i>Lactobacillus</i> Elicit High Protection against <i>Staphylococcus aureus</i> Pulmonary and Skin Infections |
| title_sort | oral delivery of novel recombinant i lactobacillus i elicit high protection against i staphylococcus aureus i pulmonary and skin infections |
| topic | <i>Staphylococcus aureus</i> oral vaccine <i>Lactobacillus</i> mucosal delivery |
| url | https://www.mdpi.com/2076-393X/9/9/984 |
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