Group A Streptococcus Vaccine Targeting the Erythrogenic Toxins SpeA and SpeB Is Safe and Immunogenic in Rabbits and Does Not Induce Antibodies Associated with Autoimmunity
Group A streptococcus (GAS) is a global pathogen associated with significant morbidity and mortality for which there is currently no licensed vaccine. Vaccine development has been slow, mostly due to safety concerns regarding streptococcal antigens associated with autoimmunity and related complicati...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-09-01
|
| Series: | Vaccines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-393X/11/9/1504 |
| _version_ | 1797576504522047488 |
|---|---|
| author | Matthew J. Troese Elodie Burlet Madeleine W. Cunningham Kathy Alvarez Rebecca Bentley Nissy Thomas Shanna Carwell Garry L. Morefield |
| author_facet | Matthew J. Troese Elodie Burlet Madeleine W. Cunningham Kathy Alvarez Rebecca Bentley Nissy Thomas Shanna Carwell Garry L. Morefield |
| author_sort | Matthew J. Troese |
| collection | DOAJ |
| description | Group A streptococcus (GAS) is a global pathogen associated with significant morbidity and mortality for which there is currently no licensed vaccine. Vaccine development has been slow, mostly due to safety concerns regarding streptococcal antigens associated with autoimmunity and related complications. For a GAS vaccine to be safe, it must be ensured that the antigens used in the vaccine do not elicit an antibody response that can cross-react with host tissues. In this study, we evaluated the safety of our GAS vaccine candidate called VaxiStrep in New Zealand White rabbits. VaxiStrep is a recombinant fusion protein comprised of streptococcal pyrogenic exotoxin A (SpeA) and exotoxin B (SpeB), also known as erythrogenic toxins, adsorbed to an aluminum adjuvant. The vaccine elicited a robust immune response against the two toxins in the rabbits without any adverse events or toxicity. No signs of autoimmune pathology were detected in the rabbits’ brains, hearts, and kidneys via immunohistochemistry, and serum antibodies did not cross-react with cardiac or neuronal tissue proteins associated with rheumatic heart disease or Sydenham chorea (SC). This study further confirms that VaxiStrep does not elicit autoantibodies and is safe to be tested in a first-in-human trial. |
| first_indexed | 2024-03-10T21:52:55Z |
| format | Article |
| id | doaj.art-c9863702893d40238175498b24db68da |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-10T21:52:55Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-c9863702893d40238175498b24db68da2023-11-19T13:19:53ZengMDPI AGVaccines2076-393X2023-09-01119150410.3390/vaccines11091504Group A Streptococcus Vaccine Targeting the Erythrogenic Toxins SpeA and SpeB Is Safe and Immunogenic in Rabbits and Does Not Induce Antibodies Associated with AutoimmunityMatthew J. Troese0Elodie Burlet1Madeleine W. Cunningham2Kathy Alvarez3Rebecca Bentley4Nissy Thomas5Shanna Carwell6Garry L. Morefield7VaxForm, LLC., Bethlehem, PA 18015, USAVaxForm, LLC., Bethlehem, PA 18015, USADepartment of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USADepartment of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USADepartment of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USAVaxForm, LLC., Bethlehem, PA 18015, USAVaxForm, LLC., Bethlehem, PA 18015, USAVaxForm, LLC., Bethlehem, PA 18015, USAGroup A streptococcus (GAS) is a global pathogen associated with significant morbidity and mortality for which there is currently no licensed vaccine. Vaccine development has been slow, mostly due to safety concerns regarding streptococcal antigens associated with autoimmunity and related complications. For a GAS vaccine to be safe, it must be ensured that the antigens used in the vaccine do not elicit an antibody response that can cross-react with host tissues. In this study, we evaluated the safety of our GAS vaccine candidate called VaxiStrep in New Zealand White rabbits. VaxiStrep is a recombinant fusion protein comprised of streptococcal pyrogenic exotoxin A (SpeA) and exotoxin B (SpeB), also known as erythrogenic toxins, adsorbed to an aluminum adjuvant. The vaccine elicited a robust immune response against the two toxins in the rabbits without any adverse events or toxicity. No signs of autoimmune pathology were detected in the rabbits’ brains, hearts, and kidneys via immunohistochemistry, and serum antibodies did not cross-react with cardiac or neuronal tissue proteins associated with rheumatic heart disease or Sydenham chorea (SC). This study further confirms that VaxiStrep does not elicit autoantibodies and is safe to be tested in a first-in-human trial.https://www.mdpi.com/2076-393X/11/9/1504Group A Streptococcus (GAS)<i>Streptococcus pyogenes</i>SpeASpeBvaccinesafety |
| spellingShingle | Matthew J. Troese Elodie Burlet Madeleine W. Cunningham Kathy Alvarez Rebecca Bentley Nissy Thomas Shanna Carwell Garry L. Morefield Group A Streptococcus Vaccine Targeting the Erythrogenic Toxins SpeA and SpeB Is Safe and Immunogenic in Rabbits and Does Not Induce Antibodies Associated with Autoimmunity Vaccines Group A Streptococcus (GAS) <i>Streptococcus pyogenes</i> SpeA SpeB vaccine safety |
| title | Group A Streptococcus Vaccine Targeting the Erythrogenic Toxins SpeA and SpeB Is Safe and Immunogenic in Rabbits and Does Not Induce Antibodies Associated with Autoimmunity |
| title_full | Group A Streptococcus Vaccine Targeting the Erythrogenic Toxins SpeA and SpeB Is Safe and Immunogenic in Rabbits and Does Not Induce Antibodies Associated with Autoimmunity |
| title_fullStr | Group A Streptococcus Vaccine Targeting the Erythrogenic Toxins SpeA and SpeB Is Safe and Immunogenic in Rabbits and Does Not Induce Antibodies Associated with Autoimmunity |
| title_full_unstemmed | Group A Streptococcus Vaccine Targeting the Erythrogenic Toxins SpeA and SpeB Is Safe and Immunogenic in Rabbits and Does Not Induce Antibodies Associated with Autoimmunity |
| title_short | Group A Streptococcus Vaccine Targeting the Erythrogenic Toxins SpeA and SpeB Is Safe and Immunogenic in Rabbits and Does Not Induce Antibodies Associated with Autoimmunity |
| title_sort | group a streptococcus vaccine targeting the erythrogenic toxins spea and speb is safe and immunogenic in rabbits and does not induce antibodies associated with autoimmunity |
| topic | Group A Streptococcus (GAS) <i>Streptococcus pyogenes</i> SpeA SpeB vaccine safety |
| url | https://www.mdpi.com/2076-393X/11/9/1504 |
| work_keys_str_mv | AT matthewjtroese groupastreptococcusvaccinetargetingtheerythrogenictoxinsspeaandspebissafeandimmunogenicinrabbitsanddoesnotinduceantibodiesassociatedwithautoimmunity AT elodieburlet groupastreptococcusvaccinetargetingtheerythrogenictoxinsspeaandspebissafeandimmunogenicinrabbitsanddoesnotinduceantibodiesassociatedwithautoimmunity AT madeleinewcunningham groupastreptococcusvaccinetargetingtheerythrogenictoxinsspeaandspebissafeandimmunogenicinrabbitsanddoesnotinduceantibodiesassociatedwithautoimmunity AT kathyalvarez groupastreptococcusvaccinetargetingtheerythrogenictoxinsspeaandspebissafeandimmunogenicinrabbitsanddoesnotinduceantibodiesassociatedwithautoimmunity AT rebeccabentley groupastreptococcusvaccinetargetingtheerythrogenictoxinsspeaandspebissafeandimmunogenicinrabbitsanddoesnotinduceantibodiesassociatedwithautoimmunity AT nissythomas groupastreptococcusvaccinetargetingtheerythrogenictoxinsspeaandspebissafeandimmunogenicinrabbitsanddoesnotinduceantibodiesassociatedwithautoimmunity AT shannacarwell groupastreptococcusvaccinetargetingtheerythrogenictoxinsspeaandspebissafeandimmunogenicinrabbitsanddoesnotinduceantibodiesassociatedwithautoimmunity AT garrylmorefield groupastreptococcusvaccinetargetingtheerythrogenictoxinsspeaandspebissafeandimmunogenicinrabbitsanddoesnotinduceantibodiesassociatedwithautoimmunity |