Nonclinical Development of BCG Replacement Vaccine Candidates
The failure of current Mycobacterium bovis bacille Calmette–Guérin (BCG) vaccines, given to neonates to protect against adult tuberculosis and the risk of using these live vaccines in HIV-infected infants, has emphasized the need for generating new, more efficacious and safer replacement vaccines. W...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2013-04-01
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| Series: | Vaccines |
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| Online Access: | http://www.mdpi.com/2076-393X/1/2/120 |
| _version_ | 1818013443312058368 |
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| author | Bernd Eisele Martin Gengenbacher Reginald Kidd David McCown Sheldon Morris Steven Derrick David Hokey Dominick Laddy Rosemary Chang Megan Fitzpatrick Leander Grode Kamalakannan Velmurugan Stefan H.E. Kaufmann John Fulkerson Michael J. Brennan |
| author_facet | Bernd Eisele Martin Gengenbacher Reginald Kidd David McCown Sheldon Morris Steven Derrick David Hokey Dominick Laddy Rosemary Chang Megan Fitzpatrick Leander Grode Kamalakannan Velmurugan Stefan H.E. Kaufmann John Fulkerson Michael J. Brennan |
| author_sort | Bernd Eisele |
| collection | DOAJ |
| description | The failure of current Mycobacterium bovis bacille Calmette–Guérin (BCG) vaccines, given to neonates to protect against adult tuberculosis and the risk of using these live vaccines in HIV-infected infants, has emphasized the need for generating new, more efficacious and safer replacement vaccines. With the availability of genetic techniques for constructing recombinant BCG (rBCG) strains containing well-defined gene deletions or insertions, new vaccine candidates are under evaluation at both the preclinical and clinical stages of development. Since most BCG vaccines in use today were evaluated in clinical trials decades ago and are produced by outdated processes, the development of new BCG vaccines offers a number of advantages that include a modern well-defined manufacturing process along with state-of-the-art evaluation of safety and efficacy in target populations. We provide a description of the preclinical development of two novel rBCGs, VPM1002 that was constructed by adding a modified hly gene coding for the protein listeriolysin O (LLO) from Listeria monocytogenes and AERAS-422, which carries a modified pfoA gene coding for the protein perfringolysin O (PFO) from Clostridium perfringens, and three genes from Mycobacterium tuberculosis. Novel approaches like these should be helpful in generating stable and effective rBCG vaccine candidates that can be better characterized than traditional BCG vaccines. |
| first_indexed | 2024-04-14T06:33:12Z |
| format | Article |
| id | doaj.art-0faed53a9b714acc8f5dbb8a8015cef0 |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-04-14T06:33:12Z |
| publishDate | 2013-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-0faed53a9b714acc8f5dbb8a8015cef02022-12-22T02:07:32ZengMDPI AGVaccines2076-393X2013-04-011212013810.3390/vaccines1020120Nonclinical Development of BCG Replacement Vaccine CandidatesBernd EiseleMartin GengenbacherReginald KiddDavid McCownSheldon MorrisSteven DerrickDavid HokeyDominick LaddyRosemary ChangMegan FitzpatrickLeander GrodeKamalakannan VelmuruganStefan H.E. KaufmannJohn FulkersonMichael J. BrennanThe failure of current Mycobacterium bovis bacille Calmette–Guérin (BCG) vaccines, given to neonates to protect against adult tuberculosis and the risk of using these live vaccines in HIV-infected infants, has emphasized the need for generating new, more efficacious and safer replacement vaccines. With the availability of genetic techniques for constructing recombinant BCG (rBCG) strains containing well-defined gene deletions or insertions, new vaccine candidates are under evaluation at both the preclinical and clinical stages of development. Since most BCG vaccines in use today were evaluated in clinical trials decades ago and are produced by outdated processes, the development of new BCG vaccines offers a number of advantages that include a modern well-defined manufacturing process along with state-of-the-art evaluation of safety and efficacy in target populations. We provide a description of the preclinical development of two novel rBCGs, VPM1002 that was constructed by adding a modified hly gene coding for the protein listeriolysin O (LLO) from Listeria monocytogenes and AERAS-422, which carries a modified pfoA gene coding for the protein perfringolysin O (PFO) from Clostridium perfringens, and three genes from Mycobacterium tuberculosis. Novel approaches like these should be helpful in generating stable and effective rBCG vaccine candidates that can be better characterized than traditional BCG vaccines.http://www.mdpi.com/2076-393X/1/2/120tuberculosislive vaccinesMycobacterium tuberculosisrecombinant BCG |
| spellingShingle | Bernd Eisele Martin Gengenbacher Reginald Kidd David McCown Sheldon Morris Steven Derrick David Hokey Dominick Laddy Rosemary Chang Megan Fitzpatrick Leander Grode Kamalakannan Velmurugan Stefan H.E. Kaufmann John Fulkerson Michael J. Brennan Nonclinical Development of BCG Replacement Vaccine Candidates Vaccines tuberculosis live vaccines Mycobacterium tuberculosis recombinant BCG |
| title | Nonclinical Development of BCG Replacement Vaccine Candidates |
| title_full | Nonclinical Development of BCG Replacement Vaccine Candidates |
| title_fullStr | Nonclinical Development of BCG Replacement Vaccine Candidates |
| title_full_unstemmed | Nonclinical Development of BCG Replacement Vaccine Candidates |
| title_short | Nonclinical Development of BCG Replacement Vaccine Candidates |
| title_sort | nonclinical development of bcg replacement vaccine candidates |
| topic | tuberculosis live vaccines Mycobacterium tuberculosis recombinant BCG |
| url | http://www.mdpi.com/2076-393X/1/2/120 |
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