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Included citation to study that used single cell transcriptome profiling to study immune responses in a challenge study. |
Included an explanation how challenge studies contributed to our knowledge on the immune responses to SARS-CoV-2 exposure. |
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{{Use dmy dates|date=August 2021}}
{{Short description|Clinical trial with intentional exposure to a pathogen}}
A '''human challenge study''', also called a '''challenge trial''' or '''controlled human infection model''' (CHIM), is a type of [[clinical trial]] for a [[vaccine]] or other [[drug|pharmaceutical]] involving the intentional exposure of the test subject to the condition tested.<ref name="lamb">{{Cite journal|last1=Lambkin-Williams|first1=Rob|last2=Noulin|first2=Nicolas|last3=Mann|first3=Alex|last4=Catchpole|first4=Andrew|last5=Gilbert|first5=Anthony S.|date=22 June 2018|title=The human viral challenge model: accelerating the evaluation of respiratory antivirals, vaccines and novel diagnostics|journal=Respiratory Research|volume=19|issue=1|pages=123|doi=10.1186/s12931-018-0784-1|issn=1465-993X|pmc=6013893|pmid=29929556 |doi-access=free }}</ref><ref name="eyal">{{Cite journal|last1=Eyal|first1=Nir|last2=Lipsitch|first2=Marc|last3=Smith|first3=Peter G.|title=Human challenge studies to accelerate coronavirus vaccine licensure|url= |journal=The Journal of Infectious Diseases|doi=10.1093/infdis/jiaa152|date=31 March 2020|volume=221|issue=11|pages=1752–1756|pmid=32232474|pmc=7184325| name-list-style = vanc }}</ref><ref name="callaway">{{Cite journal|vauthors=Callaway E |date=April 2020|title=Should scientists infect healthy people with the coronavirus to test vaccines?|journal=Nature|volume=580|issue=7801|pages=17|doi=10.1038/d41586-020-00927-3|pmid=32218549|bibcode=2020Natur.580...17C|s2cid=256820005 |doi-access=}}</ref> Human challenge studies may be ethically controversial because they involve exposing test subjects to dangers beyond those posed by potential [[side effect]]s of the substance being tested.<ref name=eyal/><ref name=callaway/> Controlled human infection studies are also used to study viruses and immune responses.<ref name="Killingley 2022">{{cite journal |last1=Killingley |first1=Ben |last2=Mann |first2=Alex J. |last3=Kalinova |first3=Mariya |last4=Boyers |first4=Alison |last5=Goonawardane |first5=Niluka |last6=Zhou |first6=Jie |last7=Lindsell |first7=Kate |last8=Hare |first8=Samanjit S. |last9=Brown |first9=Jonathan |last10=Frise |first10=Rebecca |last11=Smith |first11=Emma |last12=Hopkins |first12=Claire |last13=Noulin |first13=Nicolas |last14=Löndt |first14=Brandon |last15=Wilkinson |first15=Tom |last16=Harden |first16=Stephen |last17=McShane |first17=Helen |last18=Baillet |first18=Mark |last19=Gilbert |first19=Anthony |last20=Jacobs |first20=Michael |last21=Charman |first21=Christine |last22=Mande |first22=Priya |last23=Nguyen-Van-Tam |first23=Jonathan S. |last24=Semple |first24=Malcolm G. |last25=Read |first25=Robert C. |last26=Ferguson |first26=Neil M. |last27=Openshaw |first27=Peter J. |last28=Rapeport |first28=Garth |last29=Barclay |first29=Wendy S. |last30=Catchpole |first30=Andrew P. |last31=Chiu |first31=Christopher |title=Safety, tolerability and viral kinetics during SARS-CoV-2 human challenge in young adults |journal=Nature Medicine |date=May 2022 |volume=28 |issue=5 |pages=1031–1041 |doi=10.1038/s41591-022-01780-9 |pmid=35361992 |url=https://www.nature.com/articles/s41591-022-01780-9 |access-date=12 April 2024|hdl=10044/1/96278 |hdl-access=free }}</ref><ref name=":0">{{Cite journal |last=Lindeboom |first=Rik G. H. |last2=Worlock |first2=Kaylee B. |last3=Dratva |first3=Lisa M. |last4=Yoshida |first4=Masahiro |last5=Scobie |first5=David |last6=Wagstaffe |first6=Helen R. |last7=Richardson |first7=Laura |last8=Wilbrey-Clark |first8=Anna |last9=Barnes |first9=Josephine L. |last10=Kretschmer |first10=Lorenz |last11=Polanski |first11=Krzysztof |last12=Allen-Hyttinen |first12=Jessica |last13=Mehta |first13=Puja |last14=Sumanaweera |first14=Dinithi |last15=Boccacino |first15=Jacqueline M. |date=2024-07 |title=Human SARS-CoV-2 challenge uncovers local and systemic response dynamics |url=https://www.nature.com/articles/s41586-024-07575-x |journal=Nature |language=en |volume=631 |issue=8019 |pages=189–198 |doi=10.1038/s41586-024-07575-x |issn=1476-4687 |pmc=PMC11222146 |pmid=38898278}}</ref>
During the mid 20th and 21st century, the number of human challenge studies has been increasing.<ref name="Adams-Phipps">{{cite journal |last1=Adams-Phipps |first1=Jupiter |last2=Toomey |first2=Danny |last3=Więcek |first3=Witold|last4=Schmit |first4=Virginia|last5=Wilkinson |first5=James|last6=Scholl |first6=Keller|last7=Jamrozik |first7=Joshua|last8=Roestenberg |first8=Meta|last9=Manheim |first9=David|title=A Systematic Review of Human Challenge Trials, Designs, and Safety|journal=Clinical Infectious Diseases|date=11 October 2022 |volume=76 |issue=4 |pages=609–619 |doi=10.1093/cid/ciac820 |pmid=36219704 |pmc=9938741 |doi-access=free }}</ref><ref name="cohen16">{{cite journal|url=https://www.science.org/doi/10.1126/science.352.6288.882|title=Studies that intentionally infect people with disease-causing bugs are on the rise|first=Jon|last=Cohen|journal=Science|doi=10.1126/science.aaf5726|date=18 May 2016|volume=352 |issue=6288 |pages=882–885 }}</ref> A challenge study to test promising vaccines for prevention of [[COVID-19]] was under consideration during 2020 by several vaccine developers, including the [[World Health Organization]] (WHO),<ref name="who-chall">{{Cite web|title=Key criteria for the ethical acceptability of COVID-19 human challenge studies|url=https://apps.who.int/iris/bitstream/handle/10665/331976/WHO-2019-nCoV-Ethics_criteria-2020.1-eng.pdf|publisher=World Health Organization|date=6 May 2020|access-date=18 May 2020}}</ref><ref name="cohen20">{{Cite journal|url=https://www.science.org/content/article/speed-coronavirus-vaccine-testing-deliberately-infecting-volunteers-not-so-fast-some|title=Speed coronavirus vaccine testing by deliberately infecting volunteers? Not so fast, some scientists warn|last=Cohen|first=Jon|date=31 March 2020|journal=Science|doi=10.1126/science.abc0006|s2cid=216451224|access-date=19 April 2020}}</ref> and was approved in the UK in 2021.<ref>{{Cite web|title=World's first coronavirus Human Challenge study receives ethics approval in the UK|url=https://www.gov.uk/government/news/worlds-first-coronavirus-human-challenge-study-receives-ethics-approval-in-the-uk|access-date=18 February 2021|website=GOV.UK|language=en}}</ref>
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In May 2020, a guidance document was issued by the WHO on criteria for conducting challenge clinical trials and providing clinical care for the participants.<ref name=who-chall/> Following the challenge infection with or without the candidate vaccine, volunteers would be monitored closely in hospitals or clinics managed by physicians treating people with COVID-19 disease and with life-saving resources, if needed.<ref name=eyal/><ref name=callaway/><ref name=who-chall/> Volunteering for a vaccine challenge study during the COVID-19 pandemic is likened to the emergency service of healthcare personnel for COVID-19-infected people, [[firefighter]]s, or [[organ donation|organ donors]].<ref name=eyal/><ref name=callaway/>
Human SARS-CoV-2 challenge studies have also been performed to study the viral infection and immune response kinetics in COVID-19.<ref name="Killingley 2022" /><ref name=":0" /> Compared to patient-based studies, challenge studies offer the unique possibility to study the immune system prior to viral exposure, immediately after exposure, and in people that do not get infected upon exposure. This enabled scientists to discover a biomarker for protection, and that many distinct immune responses precede the onset of symptoms, including some also present in people that do not get infected upon exposure.<ref name=":0" />
In March 2024, funding for a five-year international consortium to develop and run human challenge studies for mucosal (transmission-blocking) Covid vaccines was announced on behalf of the [[European Union]]’s Horizon Europe Programme and the [[Coalition for Epidemic Preparedness Innovations]] (CEPI).<ref name="CEPI March 2024">{{cite web |title=Global consortium plans coordinated human challenge studies in hunt for transmission-blocking coronavirus vaccines {{!}} CEPI |url=https://cepi.net/global-consortium-plans-coordinated-human-challenge-studies-hunt-transmission-blocking-coronavirus |website=cepi.net |access-date=1 May 2024}}</ref> Called Mucosal Immunity in human Coronavirus Challenge (MusiCC) and led by [[Imperial College London]], trials are planned to take place in the UK, Europe, Singapore, and the United States.<ref name="CEPI March 2024" /> Representatives of the consortium and its Scientific Advisory Board met in April 2024 to start the project.<ref name="Imperial News Apr 2024">{{cite web |title=Imperial-led global human challenge consortium kick off ambitious 5-year project {{!}} Imperial News {{!}} Imperial College London |url=https://www.imperial.ac.uk/news/252855/imperial-led-global-human-challenge-consortium-kick/ |website=Imperial News |access-date=1 May 2024 |language=en |date=24 April 2024}}</ref> At that meeting, a speaker from CEPI said that human challenge studies were a part of the goal of achieving vaccines for new pandemic diseases in 100 days.<ref name="Imperial News Apr 2024" />
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