Poster Presentation Lorne Infection and Immunity 2023

Strategic and scientific contributions of human challenge trials for vaccine development: facts versus fantasy (#101)

Yara N Abo 1 , Andrew Steer 1 , James McCarthy 2 , Zeb Jamrozik 3 , Meta Roestenberg 4 , Josh Osowicki 1
  1. Murdoch Children's Research Institute, Melbourne, VIC, Australia
  2. Victorian Infectious Diseases Service, Royal Melbourne Hospital, Melbourne, Australia
  3. Population Health, University of Oxford, Oxford, UK
  4. Controlled Human Infections Center, Leiden University Medical Center, The Netherlands

Introduction 

Fast-tracked pandemic vaccine development has offered hope for accelerated development across a range of vaccines. Human challenge studies model an encounter between human hosts and pathogens by deliberately exposing selected volunteers to a well-characterised pathogen under controlled conditions. Human challenge trials have been proposed as a means to expedite vaccine development. They can provide early proof-of-concept for vaccine efficacy using fewer volunteers and resources, and allow the most promising candidates to advance to further phases. Human challenge can also provide correlate of protection data for use in future vaccine efficacy testing and give insights into the impact of pre-existing immunity on vaccine responses.  

Methods: 

We identify human challenge trials contributing to development of vaccines for 22 different pathogens, to discuss limitations, barriers, opportunities, and pitfalls for efforts to realise their full scientific and strategic potential. 

Results: 

Eleven vaccine candidates for 7 pathogens tested in human challenge trials have reached phase III and/or IV studies. Vaccine efficacy results in healthy adult participants have translated well to phase II field trials, with notable exceptions (e.g., influenza T-cell vaccines). Additional vaccine candidates tested in human challenge are currently in late phase trials or are soon to be tested in phase II human challenge trials. Human challenge trials have helped to down-select >40 vaccine candidates for 8 pathogens. Correlates of protection have been identified in cholera and influenza human challenge vaccine trials, and human challenge vaccine trials have provided valuable insight into correlates of protection for further enteric and respiratory pathogens as well as malaria. Limitations of human challenge trials are discussed, as well as mitigation strategies, based on findings from trials in this review. 

Conclusion: 

Human challenge trials have successfully contributed to advancement of vaccines. A focussed pathogen- and product-specific use case should be applied to maximise the contribution of human challenge research to vaccine development.