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Vaccines
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Recent Scientific Advancements towards a Vaccine against Group A Streptococcus
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Recent Scientific Advancements towards a Vaccine against Group A Streptococcus

A special issue of Vaccines (ISSN 2076-393X). This special issue belongs to the section "Pathogens-host Immune Interface".

Deadline for manuscript submissions: closed (20 March 2024) | Viewed by 9149

Special Issue Editors

Dr. Helen Alexandra Shaw

E-Mail Website
Guest Editor
The Medicines and Healthcare Regulatory Agency (MHRA), London, UK
Interests: Group A Streptococcus; vaccine research; glycoconjugate vaccines
Dr. Helge C. Dorfmueller

E-Mail Website
Guest Editor
School of Life Sciences, University of Dundee, Dundee, Scotland, UK
Interests: Streptococcus pyogenes; glycoconjugate vaccines; Group A Carbohydrate

Special Issue Information

Dear Colleagues,

Group A Streptococcus (GAS) is a major global pathogen, disproportionately affecting low- and middle- income countries, particularly through autoimmune sequelae such as acute rheumatic fever and rheumatic heart disease (RHD). The World Health Organization has highlighted the need for a GAS vaccine, with a particular focus on reducing the burden of pharyngitis as a precursor to the prevention of RHD. Despite extensive research and scientific advancements in the field, there is still a need to progress vaccine candidates into clinical trials in order to eventually get them into the market. A particular challenge is to provide broad vaccine coverage against global strains and to prevent mucosal infection without aggravating autoimmune responses. Understanding immunity through natural infection, serotype surveillance and protection in models is imperative to advance vaccines towards the market. 

The focus of this Special Issue is to bring together exciting developments and considerations for vaccine development against GAS, including epidemiological justification for vaccination or support for particular antigens. We invite you to submit your original research, reports or reviews towards the progression of a vaccine against GAS. Topics can include, but are not limited to, the following: (i) candidate antigens, (ii) correlates of protection, (iii) novel delivery methods, (iv) mucosal immunity, (v) field studies of natural infections, (vi) assay development, and vii) infection models.

Dr. Helen Alexandra Shaw
Dr. Helge C. Dorfmueller
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Vaccines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Group A Streptococcus
  • Strep A
  • S. pyogenes
  • vaccine
  • genomics
  • immunity

Published Papers (5 papers)

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Research

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15 pages, 4150 KiB  
Article
The Group A Streptococcal Vaccine Candidate VAX-A1 Protects against Group B Streptococcus Infection via Cross-Reactive IgG Targeting Virulence Factor C5a Peptidase
by Sinead McCabe, Elisabet Bjånes, Astrid Hendriks, Zhen Wang, Nina M. van Sorge, Lucy Pill-Pepe, Leslie Bautista, Ellen Chu, Jeroen D. C. Codée, Jeff Fairman, Neeraj Kapoor, Satoshi Uchiyama and Victor Nizet
Vaccines 2023, 11(12), 1811; https://doi.org/10.3390/vaccines11121811 - 3 Dec 2023
Viewed by 1880
Abstract
Group B Streptococcus (Streptococcus agalactiae or GBS) is the leading infectious cause of neonatal mortality, causing roughly 150,000 infant deaths and stillbirths annually across the globe. Approximately 20% of pregnant women are asymptomatically colonized by GBS, which is a major risk factor [...] Read more.
Group B Streptococcus (Streptococcus agalactiae or GBS) is the leading infectious cause of neonatal mortality, causing roughly 150,000 infant deaths and stillbirths annually across the globe. Approximately 20% of pregnant women are asymptomatically colonized by GBS, which is a major risk factor for severe fetal and neonatal infections as well as preterm birth, low birth weight, and neurodevelopmental abnormalities. Current clinical interventions for GBS infection are limited to antibiotics, and no vaccine is available. We previously described VAX-A1 as a highly effective conjugate vaccine against group A Streptococcus that is formulated with three antigens, SpyAD, streptolysin O, and C5a peptidase (ScpA). ScpA is a surface-expressed, well-characterized GAS virulence factor that shares nearly identical sequences with the lesser studied GBS homolog ScpB. Here, we show that GBS C5a peptidase ScpB cleaves human complement factor C5a and contributes to disease severity in the murine models of pneumonia and sepsis. Furthermore, antibodies elicited by GAS C5a peptidase bind to GBS in an ScpB-dependent manner, and VAX-A1 immunization protects mice against lethal GBS heterologous challenge. These findings support the contribution of ScpB to GBS virulence and underscore the importance of choosing vaccine antigens; a universal GAS vaccine such as VAX-A1 whose formulation includes GAS C5a peptidase may have additional benefits through some measure of cross-protection against GBS infections. Full article
(This article belongs to the Special Issue Recent Scientific Advancements towards a Vaccine against Group A Streptococcus)
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15 pages, 1181 KiB  
Article
Mucosal Immunization Has Benefits over Traditional Subcutaneous Immunization with Group A Streptococcus Antigens in a Pilot Study in a Mouse Model
by Helen Alexandra Shaw, Alex Remmington, Giselle McKenzie, Caroline Winkel and Fatme Mawas
Vaccines 2023, 11(11), 1724; https://doi.org/10.3390/vaccines11111724 - 17 Nov 2023
Viewed by 1128
Abstract
Group A Streptococcus (GAS) is a major human pathogen for which there is no licensed vaccine. To protect against infection, a strong systemic and mucosal immune response is likely to be necessary to prevent initial colonization and any events that might lead to [...] Read more.
Group A Streptococcus (GAS) is a major human pathogen for which there is no licensed vaccine. To protect against infection, a strong systemic and mucosal immune response is likely to be necessary to prevent initial colonization and any events that might lead to invasive disease. A broad immune response will be necessary to target the varied GAS serotypes and disease presentations. To this end, we designed a representative panel of recombinant proteins to cover the stages of GAS infection and investigated whether mucosal and systemic immunity could be stimulated by these protein antigens. We immunized mice sublingually, intranasally and subcutaneously, then measured IgG and IgA antibody levels and functional activity through in vitro assays. Our results show that both sublingual and intranasal immunization in the presence of adjuvant induced both systemic IgG and mucosal IgA. Meanwhile, subcutaneous immunization generated only a serum IgG response. The antibodies mediated binding and killing of GAS cells and blocked binding of GAS to HaCaT cells, particularly following intranasal and subcutaneous immunizations. Further, antigen-specific assays revealed that immune sera inhibited cleavage of IL-8 by SpyCEP and IgG by Mac/IdeS. These results demonstrate that mucosal immunization can induce effective systemic and mucosal antibody responses. This finding warrants further investigation and optimization of humoral and cellular responses as a viable alternative to subcutaneous immunization for urgently needed GAS vaccines. Full article
(This article belongs to the Special Issue Recent Scientific Advancements towards a Vaccine against Group A Streptococcus)
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18 pages, 3287 KiB  
Article
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
by Matthew J. Troese, Elodie Burlet, Madeleine W. Cunningham, Kathy Alvarez, Rebecca Bentley, Nissy Thomas, Shanna Carwell and Garry L. Morefield
Vaccines 2023, 11(9), 1504; https://doi.org/10.3390/vaccines11091504 - 20 Sep 2023
Cited by 1 | Viewed by 1625
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Recent Scientific Advancements towards a Vaccine against Group A Streptococcus)
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Review

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20 pages, 744 KiB  
Review
Recent Scientific Advancements towards a Vaccine against Group A Streptococcus
by Jingyi Fan, Istvan Toth and Rachel J. Stephenson
Vaccines 2024, 12(3), 272; https://doi.org/10.3390/vaccines12030272 - 5 Mar 2024
Viewed by 1401
Abstract
Group A Streptococcus (GAS), or Streptococcus pyogenes, is a gram-positive bacterium that extensively colonises within the human host. GAS is responsible for causing a range of human infections, such as pharyngitis, impetigo, scarlet fever, septicemia, and necrotising fasciitis. GAS pathogens have the [...] Read more.
Group A Streptococcus (GAS), or Streptococcus pyogenes, is a gram-positive bacterium that extensively colonises within the human host. GAS is responsible for causing a range of human infections, such as pharyngitis, impetigo, scarlet fever, septicemia, and necrotising fasciitis. GAS pathogens have the potential to elicit fatal autoimmune sequelae diseases (including rheumatic fever and rheumatic heart diseases) due to recurrent GAS infections, leading to high morbidity and mortality of young children and the elderly worldwide. Antibiotic drugs are the primary method of controlling and treating the early stages of GAS infection; however, the recent identification of clinical GAS isolates with reduced sensitivity to penicillin-adjunctive antibiotics and increasing macrolide resistance is an increasing threat. Vaccination is credited as the most successful medical intervention against infectious diseases since it was discovered by Edward Jenner in 1796. Immunisation with an inactive/live-attenuated whole pathogen or selective pathogen-derived antigens induces a potent adaptive immunity and protection against infectious diseases. Although no GAS vaccines have been approved for the market following more than 100 years of GAS vaccine development, the understanding of GAS pathogenesis and transmission has significantly increased, providing detailed insight into the primary pathogenic proteins, and enhancing GAS vaccine design. This review highlights recent advances in GAS vaccine development, providing detailed data from preclinical and clinical studies across the globe for potential GAS vaccine candidates. Furthermore, the challenges and future perspectives on the development of GAS vaccines are also described. Full article
(This article belongs to the Special Issue Recent Scientific Advancements towards a Vaccine against Group A Streptococcus)
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14 pages, 309 KiB  
Review
Streptococcus pyogenes: Pathogenesis and the Current Status of Vaccines
by Jiachao Wang, Cuiqing Ma, Miao Li, Xue Gao, Hao Wu, Wenbin Dong and Lin Wei
Vaccines 2023, 11(9), 1510; https://doi.org/10.3390/vaccines11091510 - 21 Sep 2023
Cited by 4 | Viewed by 2392
Abstract
Streptococcus pyogenes (group A Streptococcus; GAS), a Gram-positive coccal bacterium, poses a significant global disease burden, especially in low- and middle-income countries. Its manifestations can range from pharyngitis and skin infection to severe and aggressive diseases, such as necrotizing fasciitis and streptococcal [...] Read more.
Streptococcus pyogenes (group A Streptococcus; GAS), a Gram-positive coccal bacterium, poses a significant global disease burden, especially in low- and middle-income countries. Its manifestations can range from pharyngitis and skin infection to severe and aggressive diseases, such as necrotizing fasciitis and streptococcal toxic shock syndrome. At present, although GAS is still sensitive to penicillin, there are cases of treatment failure for GAS pharyngitis, and antibiotic therapy does not universally prevent subsequent disease. In addition to strengthening global molecular epidemiological surveillance and monitoring of antibiotic resistance, developing a safe and effective licensed vaccine against GAS would be the most effective way to broadly address GAS-related diseases. Over the past decades, the development of GAS vaccines has been stalled, mainly because of the wide genetic heterogeneity of GAS and the diverse autoimmune responses to GAS. With outbreaks of scarlet fever in various countries in recent years, accelerating the development of a safe and effective vaccine remains a high priority. When developing a GAS vaccine, many factors need to be considered, including the selection of antigen epitopes, avoidance of self-response, and vaccine coverage. Given the challenges in GAS vaccine development, this review describes the important virulence factors that induce disease by GAS infection and how this has influenced the progression of vaccine development efforts, focusing on several candidate vaccines that are further along in development. Full article
(This article belongs to the Special Issue Recent Scientific Advancements towards a Vaccine against Group A Streptococcus)
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