A phase 1 randomized controlled trial of a peptide-based group A streptococcal vaccine in healthy volunteers
Abstract Background Group A streptococci (Strep A) orStreptococcus pyogenes is a major human pathogen causing an estimated 500,000 deaths worldwide each year. Disease can range from mild pharyngitis to more severe infections, such as necrotizing fasciitis, septicemia, and toxic shock syndrome. Untre...
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2024-11-01
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| Online Access: | https://doi.org/10.1186/s13063-024-08634-4 |
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| author | Vanessa Meier-Stephenson Michael T. Hawkes Catherine Burton Ainslie Calcutt Chris Davis Jessica Dooley Michael Good Michael Houghton Eloise Keeffe Kelly Kim Ailin Lepletier Conar O’Neil Ijeoma Ogbuehi Victoria Ozberk Manisha Pandey Simone Reynolds Avi Seth William Stokes Alena Tse-Chang Ben Tyrrell D. Lorne Tyrrell Gregory J. Tyrrell Maryna Yaskina |
| author_facet | Vanessa Meier-Stephenson Michael T. Hawkes Catherine Burton Ainslie Calcutt Chris Davis Jessica Dooley Michael Good Michael Houghton Eloise Keeffe Kelly Kim Ailin Lepletier Conar O’Neil Ijeoma Ogbuehi Victoria Ozberk Manisha Pandey Simone Reynolds Avi Seth William Stokes Alena Tse-Chang Ben Tyrrell D. Lorne Tyrrell Gregory J. Tyrrell Maryna Yaskina |
| author_sort | Vanessa Meier-Stephenson |
| collection | DOAJ |
| description | Abstract Background Group A streptococci (Strep A) orStreptococcus pyogenes is a major human pathogen causing an estimated 500,000 deaths worldwide each year. Disease can range from mild pharyngitis to more severe infections, such as necrotizing fasciitis, septicemia, and toxic shock syndrome. Untreated, Strep A infection can lead to the serious post streptococcal pathologies of rheumatic fever/rheumatic heart disease and post-streptococcal glomerulonephritis. An effective vaccine against Strep A would have great benefits worldwide. Here, we test two products, J8 and p*17—both peptide derivatives of a highly conserved region in the M protein, in combination with the protein subunit K4S2 of SpyCEP, an IL-8 protease associated with neutrophil chemoattraction. Each peptide is individually conjugated to cross reacting material (CRM197), and the conjugated peptide vaccines are abbreviated as J8-K4S2 or p*17-K4S2. Methods This single-site phase I, two-stage clinical trial in Edmonton, Alberta, Canada, aims to recruit a total of 30 healthy volunteers, aged 18–45 years, without any evidence of pre-existing valvular heart disease. The trial is divided into the initial unblinded safety test dose stage (stage 1) and the randomized, double-blinded, controlled trial stage (stage 2). Stage 1 will recruit 10 volunteers—5 each to receive either J8-K4S2 or p*17-K4S2 in an unblinded, staggered fashion, whereby volunteers are dosed with intentional spacing of at least 2 days in between doses to monitor for any immediate side effects before dosing the next. Once all 5 volunteers have received 3 doses of the first test vaccine, a similar process will follow for the second test vaccine. Once safety is established in stage 1, we will proceed to stage 2, which will recruit 20 volunteers to our 3-arm randomized controlled trial (RCT), receiving either of the trial vaccines, J8-K4S2 or p*17-K4S2, or comparator (rabies) vaccine. All product dosing will be at 0, 3, and 6 weeks. The primary outcome is vaccine safety; the secondary outcome is immunogenicity and comparative analyses of the different vaccine regimens. Discussion This Strep A vaccine clinical trial aims to investigate safety and immunogenicity of two novel conjugated peptide-based vaccines, J8-KS42 and p*17-K4S2. If one or both vaccine products demonstrate favorable primary and secondary outcomes, the product(s) will move into phase II and III studies. Trial registration ClinicalTrials.gov Identifier: NCT04882514. Registered on 2021–05-12, https://clinicaltrials.gov/study/NCT04882514 . |
| format | Article |
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| institution | Kabale University |
| issn | 1745-6215 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Trials |
| spelling | doaj-art-3b507af6859c43d3b742a62462d6dfde2024-11-24T12:42:04ZengBMCTrials1745-62152024-11-0125111610.1186/s13063-024-08634-4A phase 1 randomized controlled trial of a peptide-based group A streptococcal vaccine in healthy volunteersVanessa Meier-Stephenson0Michael T. Hawkes1Catherine Burton2Ainslie Calcutt3Chris Davis4Jessica Dooley5Michael Good6Michael Houghton7Eloise Keeffe8Kelly Kim9Ailin Lepletier10Conar O’Neil11Ijeoma Ogbuehi12Victoria Ozberk13Manisha Pandey14Simone Reynolds15Avi Seth16William Stokes17Alena Tse-Chang18Ben Tyrrell19D. Lorne Tyrrell20Gregory J. Tyrrell21Maryna Yaskina22Department of Medicine/Division of Infectious Diseases, University of AlbertaLi Ka Shing Institute of Virology, University of AlbertaDepartment of Pediatrics, University of AlbertaLaboratory of Vaccines for the Developing World, Institute for Biomedicine and Glycomics, Griffith UniversityLaboratory of Vaccines for the Developing World, Institute for Biomedicine and Glycomics, Griffith UniversityLaboratory of Vaccines for the Developing World, Institute for Biomedicine and Glycomics, Griffith UniversityDepartment of Medical Microbiology and Immunology, University of AlbertaLi Ka Shing Institute of Virology, University of AlbertaLaboratory of Vaccines for the Developing World, Institute for Biomedicine and Glycomics, Griffith UniversityClinical Trials Office, University of AlbertaLaboratory of Vaccines for the Developing World, Institute for Biomedicine and Glycomics, Griffith UniversityDepartment of Medicine/Division of Infectious Diseases, University of AlbertaClinical Trials Office, University of AlbertaLaboratory of Vaccines for the Developing World, Institute for Biomedicine and Glycomics, Griffith UniversityLaboratory of Vaccines for the Developing World, Institute for Biomedicine and Glycomics, Griffith UniversityLaboratory of Vaccines for the Developing World, Institute for Biomedicine and Glycomics, Griffith UniversityClinical Trials Office, University of AlbertaDepartment of Medicine/Division of Infectious Diseases, University of AlbertaDepartment of Pediatrics, University of AlbertaDepartment of Medicine/Division of Cardiology, University of AlbertaLi Ka Shing Institute of Virology, University of AlbertaDepartment Laboratory Medicine & Pathology, University of AlbertaFaculty of Medicine and Dentistry, University of AlbertaAbstract Background Group A streptococci (Strep A) orStreptococcus pyogenes is a major human pathogen causing an estimated 500,000 deaths worldwide each year. Disease can range from mild pharyngitis to more severe infections, such as necrotizing fasciitis, septicemia, and toxic shock syndrome. Untreated, Strep A infection can lead to the serious post streptococcal pathologies of rheumatic fever/rheumatic heart disease and post-streptococcal glomerulonephritis. An effective vaccine against Strep A would have great benefits worldwide. Here, we test two products, J8 and p*17—both peptide derivatives of a highly conserved region in the M protein, in combination with the protein subunit K4S2 of SpyCEP, an IL-8 protease associated with neutrophil chemoattraction. Each peptide is individually conjugated to cross reacting material (CRM197), and the conjugated peptide vaccines are abbreviated as J8-K4S2 or p*17-K4S2. Methods This single-site phase I, two-stage clinical trial in Edmonton, Alberta, Canada, aims to recruit a total of 30 healthy volunteers, aged 18–45 years, without any evidence of pre-existing valvular heart disease. The trial is divided into the initial unblinded safety test dose stage (stage 1) and the randomized, double-blinded, controlled trial stage (stage 2). Stage 1 will recruit 10 volunteers—5 each to receive either J8-K4S2 or p*17-K4S2 in an unblinded, staggered fashion, whereby volunteers are dosed with intentional spacing of at least 2 days in between doses to monitor for any immediate side effects before dosing the next. Once all 5 volunteers have received 3 doses of the first test vaccine, a similar process will follow for the second test vaccine. Once safety is established in stage 1, we will proceed to stage 2, which will recruit 20 volunteers to our 3-arm randomized controlled trial (RCT), receiving either of the trial vaccines, J8-K4S2 or p*17-K4S2, or comparator (rabies) vaccine. All product dosing will be at 0, 3, and 6 weeks. The primary outcome is vaccine safety; the secondary outcome is immunogenicity and comparative analyses of the different vaccine regimens. Discussion This Strep A vaccine clinical trial aims to investigate safety and immunogenicity of two novel conjugated peptide-based vaccines, J8-KS42 and p*17-K4S2. If one or both vaccine products demonstrate favorable primary and secondary outcomes, the product(s) will move into phase II and III studies. Trial registration ClinicalTrials.gov Identifier: NCT04882514. Registered on 2021–05-12, https://clinicaltrials.gov/study/NCT04882514 .https://doi.org/10.1186/s13063-024-08634-4Group A streptococcus (GAS; Strep a)Phase I vaccine clinical trialM proteinSpy-CEPStreptococcus pyogenes |
| spellingShingle | Vanessa Meier-Stephenson Michael T. Hawkes Catherine Burton Ainslie Calcutt Chris Davis Jessica Dooley Michael Good Michael Houghton Eloise Keeffe Kelly Kim Ailin Lepletier Conar O’Neil Ijeoma Ogbuehi Victoria Ozberk Manisha Pandey Simone Reynolds Avi Seth William Stokes Alena Tse-Chang Ben Tyrrell D. Lorne Tyrrell Gregory J. Tyrrell Maryna Yaskina A phase 1 randomized controlled trial of a peptide-based group A streptococcal vaccine in healthy volunteers Trials Group A streptococcus (GAS; Strep a) Phase I vaccine clinical trial M protein Spy-CEP Streptococcus pyogenes |
| title | A phase 1 randomized controlled trial of a peptide-based group A streptococcal vaccine in healthy volunteers |
| title_full | A phase 1 randomized controlled trial of a peptide-based group A streptococcal vaccine in healthy volunteers |
| title_fullStr | A phase 1 randomized controlled trial of a peptide-based group A streptococcal vaccine in healthy volunteers |
| title_full_unstemmed | A phase 1 randomized controlled trial of a peptide-based group A streptococcal vaccine in healthy volunteers |
| title_short | A phase 1 randomized controlled trial of a peptide-based group A streptococcal vaccine in healthy volunteers |
| title_sort | phase 1 randomized controlled trial of a peptide based group a streptococcal vaccine in healthy volunteers |
| topic | Group A streptococcus (GAS; Strep a) Phase I vaccine clinical trial M protein Spy-CEP Streptococcus pyogenes |
| url | https://doi.org/10.1186/s13063-024-08634-4 |
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