Safety of Streptococcus pyogenes Vaccines: Anticipating and Overcoming Challenges for Clinical Trials and Post-Marketing Monitoring.

Streptococcus pyogenes (Strep A) infections result in a vastly underestimated burden of acute and chronic disease globally. The Strep A Vaccine Global Consortium's (SAVAC's) mission is to accelerate the development of safe, effective, and affordable S. pyogenes vaccines. The safety of vaccine recipients is of paramount importance. A single S. pyogenes vaccine clinical trial conducted in the 1960s raised important safety concerns. A SAVAC Safety Working Group was established to review the safety assessment methodology and results of more recent early-phase clinical trials and to consider future challenges for vaccine safety assessments across all phases of vaccine development. No clinical or biological safety signals were detected in any of these early-phase trials in the modern era. Improvements in vaccine safety assessments need further consideration, particularly for pediatric clinical trials, large-scale efficacy trials, and preparation for post-marketing pharmacovigilance.

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© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.

Déclaration de conflit d'intérêts

Potential conflicts of interest. E. J. A. is a member of the SAVAC Executive Committee. J. L. E. is member of SAVAC, an employee of IVI, and chair of a safety monitoring committee and a data and safety monitoring board (DSMB) for the US Military HIV Research Program. M. M. is past president of the International Pediatric Transplant Association (IPTA), current president of the South African Transplant Society, and reports IPTA Congress travel and accommodation as past president. S. S. declares membership of the SAVAC Executive Committee (a nonremunerated position). W. S. has participated in advisory boards for other vaccines not related to group A Streptococcus, is an independent consultant with multiple clients developing vaccines (none developing a group A Streptococcus vaccine), and owns stocks in ModernaTX, Inc. L. Z. is a member of the SAVAC Executive Committee (unpaid); is funded by SAMRC through its Division of Research Capacity Development under the Mid-Career Scientist Programme from funding received from the South African National Treasury; receives support from the National Research Foundation of South Africa, the UK Medical Research Council (MRC), and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreement via the African Research Leader Award; is a board member of the World Heart Federation, Non-communicable Diseases Alliance, and Food Forward SA; and received funding for contributions to UpToDate. J. H. K. is chair of SAVAC, an SK bioscience coronavirus disease (COVID) consultant, and an Everest unpaid COVID consultant. J. B. D. is the inventor of certain technologies related to the development of group A streptococcal vaccines (the intellectual property is owned by the University of Tennessee Research Foundation and has not been outlicensed), is a member of a DSMB for the Variation Biotechnologies vaccine program, and reports research funding from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (NIH) and Moderna. A. C. S. is co-chair of SAVAC (unpaid); president of the Lancefield Society for Streptococci and Streptococcal Diseases (unpaid); co-director of the ASAVI (unpaid); co-chair of the SAVAC (unpaid); reports funding from the Australian government’s National Health and Medical Research Council and Medical Research Future Fund, the US government’s NIH, the Viertel Foundation, the Macquarie Foundation, the Royal Children's Hospital Melbourne Foundation, and the Thrasher Foundation; and is a member of the DSMB for studies of moxidectin sponsored by Medicines Development for Global Health. J. A. reports consulting fees paid to employer by ASAVI and by IAVI. E. J. A. reports research grants to the University of Colorado from Pfizer Vaccines; consulting fees for serving on an advisory board for Moderna vaccines; support for attending meetings from SAVAC; and participation on a DSMB or advisory board for Curevac, Inovio, and IVI. All remaining authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.