A Universal Vaccine against Leptospirosis: Are We Going in the Right Direction?
Leptospirosis is the most widespread zoonosis in the world and a neglected tropical disease estimated to cause severe infection in more than one million people worldwide every year that can be combated by effective immunization. However, no significant progress has been made on the leptospirosis vac...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2017-03-01
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| Series: | Frontiers in Immunology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fimmu.2017.00256/full |
| _version_ | 1818114431172739072 |
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| author | André Alex Grassmann Jéssica Dias Souza Alan John Alexander McBride Alan John Alexander McBride |
| author_facet | André Alex Grassmann Jéssica Dias Souza Alan John Alexander McBride Alan John Alexander McBride |
| author_sort | André Alex Grassmann |
| collection | DOAJ |
| description | Leptospirosis is the most widespread zoonosis in the world and a neglected tropical disease estimated to cause severe infection in more than one million people worldwide every year that can be combated by effective immunization. However, no significant progress has been made on the leptospirosis vaccine since the advent of bacterins over 100 years. Although protective against lethal infection, particularly in animals, bacterin-induced immunity is considered short term, serovar restricted, and the vaccine can cause serious side effects. The urgent need for a new vaccine has motivated several research groups to evaluate the protective immune response induced by recombinant vaccines. Significant protection has been reported with several promising outer membrane proteins, including LipL32 and the leptospiral immunoglobulin-like proteins. However, efficacy was variable and failed to induce a cross-protective response or sterile immunity among vaccinated animals. As hundreds of draft genomes of all known Leptospira species are now available, this should aid novel target discovery through reverse vaccinology (RV) and pangenomic studies. The identification of surface-exposed vaccine candidates that are highly conserved among infectious Leptospira spp. is a requirement for the development of a cross-protective universal vaccine. However, the lack of immune correlates is a major drawback to the application of RV to Leptospira genomes. In addition, as the protective immune response against leptospirosis is not fully understood, the rational use of adjuvants tends to be a process of trial and error. In this perspective, we discuss current advances, the pitfalls, and possible solutions for the development of a universal leptospirosis vaccine. |
| first_indexed | 2024-12-11T03:50:37Z |
| format | Article |
| id | doaj.art-17d5f9763e6840f5a14ff527858393bd |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-11T03:50:37Z |
| publishDate | 2017-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-17d5f9763e6840f5a14ff527858393bd2022-12-22T01:21:55ZengFrontiers Media S.A.Frontiers in Immunology1664-32242017-03-01810.3389/fimmu.2017.00256246909A Universal Vaccine against Leptospirosis: Are We Going in the Right Direction?André Alex Grassmann0Jéssica Dias Souza1Alan John Alexander McBride2Alan John Alexander McBride3Biotechnology Unit, Technological Development Centre, Federal University of Pelotas, Pelotas, BrazilBiotechnology Unit, Technological Development Centre, Federal University of Pelotas, Pelotas, BrazilBiotechnology Unit, Technological Development Centre, Federal University of Pelotas, Pelotas, BrazilGonçalo Moniz Institute, Oswaldo Cruz Foundation, Ministry of Health, Salvador, BrazilLeptospirosis is the most widespread zoonosis in the world and a neglected tropical disease estimated to cause severe infection in more than one million people worldwide every year that can be combated by effective immunization. However, no significant progress has been made on the leptospirosis vaccine since the advent of bacterins over 100 years. Although protective against lethal infection, particularly in animals, bacterin-induced immunity is considered short term, serovar restricted, and the vaccine can cause serious side effects. The urgent need for a new vaccine has motivated several research groups to evaluate the protective immune response induced by recombinant vaccines. Significant protection has been reported with several promising outer membrane proteins, including LipL32 and the leptospiral immunoglobulin-like proteins. However, efficacy was variable and failed to induce a cross-protective response or sterile immunity among vaccinated animals. As hundreds of draft genomes of all known Leptospira species are now available, this should aid novel target discovery through reverse vaccinology (RV) and pangenomic studies. The identification of surface-exposed vaccine candidates that are highly conserved among infectious Leptospira spp. is a requirement for the development of a cross-protective universal vaccine. However, the lack of immune correlates is a major drawback to the application of RV to Leptospira genomes. In addition, as the protective immune response against leptospirosis is not fully understood, the rational use of adjuvants tends to be a process of trial and error. In this perspective, we discuss current advances, the pitfalls, and possible solutions for the development of a universal leptospirosis vaccine.http://journal.frontiersin.org/article/10.3389/fimmu.2017.00256/fullLeptospirareverse vaccinologygenome miningvaccine discoveryvaccine candidaterecombinant vaccine |
| spellingShingle | André Alex Grassmann Jéssica Dias Souza Alan John Alexander McBride Alan John Alexander McBride A Universal Vaccine against Leptospirosis: Are We Going in the Right Direction? Frontiers in Immunology Leptospira reverse vaccinology genome mining vaccine discovery vaccine candidate recombinant vaccine |
| title | A Universal Vaccine against Leptospirosis: Are We Going in the Right Direction? |
| title_full | A Universal Vaccine against Leptospirosis: Are We Going in the Right Direction? |
| title_fullStr | A Universal Vaccine against Leptospirosis: Are We Going in the Right Direction? |
| title_full_unstemmed | A Universal Vaccine against Leptospirosis: Are We Going in the Right Direction? |
| title_short | A Universal Vaccine against Leptospirosis: Are We Going in the Right Direction? |
| title_sort | universal vaccine against leptospirosis are we going in the right direction |
| topic | Leptospira reverse vaccinology genome mining vaccine discovery vaccine candidate recombinant vaccine |
| url | http://journal.frontiersin.org/article/10.3389/fimmu.2017.00256/full |
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