Controlled human infection for vaccination against Streptococcus pyogenes (CHIVAS): Establishing a group A Streptococcus pharyngitis human infection study

Joshua Osowicki, Kristy I. Azzopardi, Ciara Baker, Claire S. Waddington, Manisha Pandey, Tibor Schuster, Anneke Grobler, Allen C. Cheng, Andrew J. Pollard, James S. McCarthy, Michael F. Good, Mark J. Walker, James Dale, Michael R. Batzloff, Jonathan R. Carapetis, Pierre R. Smeesters, Andrew C. Steer

Research output: Contribution to journalArticle

Abstract

Group A Streptococcus (GAS) is a highly-adapted and human-restricted pathogen responsible for a high global burden of disease across a diverse clinical spectrum. Vaccine development has been impeded by scientific, regulatory, and commercial obstacles. Human infection studies (HIS) are increasingly contributing to drug, diagnostics, and vaccine development, reducing uncertainty at early stages, especially for pathogens with animal models that incompletely reproduce key elements of human disease. We review the small number of historical GAS HIS and present the study protocol for a dose-ranging inpatient study in healthy adults. The primary objective of the study is to establish a new GAS pharyngitis HIS with an attack rate of at least 60% as a safe and reliable platform for vaccine evaluation and pathogenesis research. According to an adaptive dose-ranging study design, emm75 GAS doses manufactured in keeping with principles of Good Manufacturing Practice will be directly applied by swab to the pharynx of carefully screened healthy adult volunteers at low risk of severe complicated GAS disease. Participants will remain as closely monitored inpatients for up to six days, observed for development of the primary outcome of acute symptomatic pharyngitis, as defined by clinical and microbiological criteria. All participants will be treated with antibiotics and followed as outpatients for six months. An intensive sampling schedule will facilitate extensive studies of host and organism dynamics during experimental pharyngitis. Ethics approval has been obtained and the study has been registered at ClinicalTrials.gov (NCT03361163).

Original languageEnglish (US)
Pages (from-to)3485-3494
Number of pages10
JournalVaccine
Volume37
Issue number26
DOIs
StatePublished - Jun 6 2019

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Streptococcus pyogenes
Pharyngitis
Streptococcus
Vaccination
vaccination
Infection
infection
Vaccines
vaccine development
Inpatients
dosage
microbiological criteria
good manufacturing practices
burden of disease
pathogens
pharynx
ethics
Pharynx
human diseases
Ethics

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Immunology and Microbiology(all)
  • veterinary(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

Cite this

Controlled human infection for vaccination against Streptococcus pyogenes (CHIVAS) : Establishing a group A Streptococcus pharyngitis human infection study. / Osowicki, Joshua; Azzopardi, Kristy I.; Baker, Ciara; Waddington, Claire S.; Pandey, Manisha; Schuster, Tibor; Grobler, Anneke; Cheng, Allen C.; Pollard, Andrew J.; McCarthy, James S.; Good, Michael F.; Walker, Mark J.; Dale, James; Batzloff, Michael R.; Carapetis, Jonathan R.; Smeesters, Pierre R.; Steer, Andrew C.

In: Vaccine, Vol. 37, No. 26, 06.06.2019, p. 3485-3494.

Research output: Contribution to journalArticle

Osowicki, J, Azzopardi, KI, Baker, C, Waddington, CS, Pandey, M, Schuster, T, Grobler, A, Cheng, AC, Pollard, AJ, McCarthy, JS, Good, MF, Walker, MJ, Dale, J, Batzloff, MR, Carapetis, JR, Smeesters, PR & Steer, AC 2019, 'Controlled human infection for vaccination against Streptococcus pyogenes (CHIVAS): Establishing a group A Streptococcus pharyngitis human infection study', Vaccine, vol. 37, no. 26, pp. 3485-3494. https://doi.org/10.1016/j.vaccine.2019.03.059
Osowicki, Joshua ; Azzopardi, Kristy I. ; Baker, Ciara ; Waddington, Claire S. ; Pandey, Manisha ; Schuster, Tibor ; Grobler, Anneke ; Cheng, Allen C. ; Pollard, Andrew J. ; McCarthy, James S. ; Good, Michael F. ; Walker, Mark J. ; Dale, James ; Batzloff, Michael R. ; Carapetis, Jonathan R. ; Smeesters, Pierre R. ; Steer, Andrew C. / Controlled human infection for vaccination against Streptococcus pyogenes (CHIVAS) : Establishing a group A Streptococcus pharyngitis human infection study. In: Vaccine. 2019 ; Vol. 37, No. 26. pp. 3485-3494.
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