Comprehensive review of safety in Experimental Human Pneumococcal Challenge

Ryan Robinson; Christopher Myerscough; Nengjie He; Helen Hill; Wendi A. Shepherd; Patricia Gonzalez-Dias; Kostas Liatsikos; Samuel Latham; Fred Fyles; Klara Doherty; Phoebe Hazenberg; Fathimath Shiham; Daniella Mclenghan; Hugh Adler; Vicki Randles; Seher Zaidi; Angela Hyder-Wright; Elena Mitsi; Hassan Burhan; Benjamin Morton; Jamie Rylance; Maia Lesosky; Stephen Gordon; Andrea Collins; Daniela Ferreira

doi:10.1371/journal.pone.0284399

Comprehensive review of safety in Experimental Human Pneumococcal Challenge

Ryan Robinson, Christopher Myerscough, Nengjie He, Helen Hill, Wendi A. Shepherd, Patricia Gonzalez-Dias, Kostas Liatsikos, Samuel Latham, Fred Fyles, Klara Doherty, Phoebe Hazenberg, Fathimath Shiham, Daniella Mclenghan, Hugh Adler, Vicki Randles, Seher Zaidi, Angela Hyder-Wright, Elena Mitsi, Hassan Burhan, Benjamin MortonJamie Rylance, Maia Lesosky, Stephen Gordon, Andrea Collins, Daniela Ferreira

Research output: Contribution to journal › Article › peer-review

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Abstract

Introduction:

Experimental Human Pneumococcal Challenge (EHPC) involves the controlled exposure of adults to a specific antibiotic-sensitive Streptococcus pneumoniae serotype, to induce nasopharyngeal colonisation for the purpose of vaccine research. The aims are to review comprehensively the safety profile of EHPC, explore the association between pneumococcal colonisation and frequency of safety review and describe the medical intervention required to undertake such studies.

Methods:

A single-centre review of all EHPC studies performed 2011–2021. All recorded serious adverse events (SAE) in eligible studies are reported. An unblinded meta-analysis of collated anonymised individual patient data from eligible EHPC studies was undertaken to assess the association between experimental pneumococcal colonisation and the frequency of safety events following inoculation.

Results:

In 1416 individuals (median age 21, IQR 20–25), 1663 experimental pneumococcal inoculations were performed. No pneumococcal-related SAE have occurred. 214 safety review events were identified with 182 (12.85%) participants presenting with symptoms potentially in keeping with pneumococcal infection, predominantly in pneumococcal colonised individuals (colonised = 96/658, non-colonised = 86/1005, OR 1.81 (95% CI 1.28–2.56, P = <0.001). The majority were mild (pneumococcal group = 72.7% [120/165 reported symptoms], non-pneumococcal = 86.7% [124/143 reported symptoms]). 1.6% (23/1416) required antibiotics for safety.

Discussion:

No SAEs were identified directly relating to pneumococcal inoculation. Safety review for symptoms was infrequent but occurred more in experimentally colonised participants. Most symptoms were mild and resolved with conservative management. A small minority required antibiotics, notably those serotype 3 inoculated.

Conclusion:

Outpatient human pneumococcal challenge can be conducted safely with appropriate levels of safety monitoring procedures in place.

Original language	English
Article number	e0284399
Pages (from-to)	e0284399
Journal	PLoS ONE
Volume	18
Issue number	5 May
Early online date	4 May 2023
DOIs	https://doi.org/10.1371/journal.pone.0284399
Publication status	Published - 4 May 2023

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Safety, Diagnostics, and Serotype Expansion in a Human Pneumococcal Challenge Model Involving Healthy Participants
Robinson, R. (Author), Collins, A. (Supervisor), Ferreira, D. (Supervisor) & Mitsi, E. (Supervisor), 2024
Student thesis: Doctoral thesis

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Robinson, R., Myerscough, C., He, N., Hill, H., Shepherd, W. A., Gonzalez-Dias, P., Liatsikos, K., Latham, S., Fyles, F., Doherty, K., Hazenberg, P., Shiham, F., Mclenghan, D., Adler, H., Randles, V., Zaidi, S., Hyder-Wright, A., Mitsi, E., Burhan, H., ... Ferreira, D. (2023). Comprehensive review of safety in Experimental Human Pneumococcal Challenge. PLoS ONE, 18(5 May), e0284399. Article e0284399. https://doi.org/10.1371/journal.pone.0284399

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title = "Comprehensive review of safety in Experimental Human Pneumococcal Challenge",

abstract = "Introduction:Experimental Human Pneumococcal Challenge (EHPC) involves the controlled exposure of adults to a specific antibiotic-sensitive Streptococcus pneumoniae serotype, to induce nasopharyngeal colonisation for the purpose of vaccine research. The aims are to review comprehensively the safety profile of EHPC, explore the association between pneumococcal colonisation and frequency of safety review and describe the medical intervention required to undertake such studies.Methods:A single-centre review of all EHPC studies performed 2011–2021. All recorded serious adverse events (SAE) in eligible studies are reported. An unblinded meta-analysis of collated anonymised individual patient data from eligible EHPC studies was undertaken to assess the association between experimental pneumococcal colonisation and the frequency of safety events following inoculation.Results:In 1416 individuals (median age 21, IQR 20–25), 1663 experimental pneumococcal inoculations were performed. No pneumococcal-related SAE have occurred. 214 safety review events were identified with 182 (12.85\%) participants presenting with symptoms potentially in keeping with pneumococcal infection, predominantly in pneumococcal colonised individuals (colonised = 96/658, non-colonised = 86/1005, OR 1.81 (95\% CI 1.28–2.56, P = <0.001). The majority were mild (pneumococcal group = 72.7\% [120/165 reported symptoms], non-pneumococcal = 86.7\% [124/143 reported symptoms]). 1.6\% (23/1416) required antibiotics for safety.Discussion:No SAEs were identified directly relating to pneumococcal inoculation. Safety review for symptoms was infrequent but occurred more in experimentally colonised participants. Most symptoms were mild and resolved with conservative management. A small minority required antibiotics, notably those serotype 3 inoculated.Conclusion:Outpatient human pneumococcal challenge can be conducted safely with appropriate levels of safety monitoring procedures in place.",

author = "Ryan Robinson and Christopher Myerscough and Nengjie He and Helen Hill and Shepherd, \{Wendi A.\} and Patricia Gonzalez-Dias and Kostas Liatsikos and Samuel Latham and Fred Fyles and Klara Doherty and Phoebe Hazenberg and Fathimath Shiham and Daniella Mclenghan and Hugh Adler and Vicki Randles and Seher Zaidi and Angela Hyder-Wright and Elena Mitsi and Hassan Burhan and Benjamin Morton and Jamie Rylance and Maia Lesosky and Stephen Gordon and Andrea Collins and Daniela Ferreira",

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volume = "18",

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Robinson, R, Myerscough, C, He, N, Hill, H, Shepherd, WA, Gonzalez-Dias, P, Liatsikos, K, Latham, S, Fyles, F, Doherty, K, Hazenberg, P, Shiham, F, Mclenghan, D, Adler, H, Randles, V, Zaidi, S, Hyder-Wright, A, Mitsi, E, Burhan, H, Morton, B, Rylance, J, Lesosky, M, Gordon, S , Collins, A & Ferreira, D 2023, 'Comprehensive review of safety in Experimental Human Pneumococcal Challenge', PLoS ONE, vol. 18, no. 5 May, e0284399, pp. e0284399. https://doi.org/10.1371/journal.pone.0284399

TY - JOUR

T1 - Comprehensive review of safety in Experimental Human Pneumococcal Challenge

AU - Robinson, Ryan

AU - Myerscough, Christopher

AU - He, Nengjie

AU - Hill, Helen

AU - Shepherd, Wendi A.

AU - Gonzalez-Dias, Patricia

AU - Liatsikos, Kostas

AU - Latham, Samuel

AU - Fyles, Fred

AU - Doherty, Klara

AU - Hazenberg, Phoebe

AU - Shiham, Fathimath

AU - Mclenghan, Daniella

AU - Adler, Hugh

AU - Randles, Vicki

AU - Zaidi, Seher

AU - Hyder-Wright, Angela

AU - Mitsi, Elena

AU - Burhan, Hassan

AU - Morton, Benjamin

AU - Rylance, Jamie

AU - Lesosky, Maia

AU - Gordon, Stephen

AU - Collins, Andrea

AU - Ferreira, Daniela

PY - 2023/5/4

Y1 - 2023/5/4

N2 - Introduction:Experimental Human Pneumococcal Challenge (EHPC) involves the controlled exposure of adults to a specific antibiotic-sensitive Streptococcus pneumoniae serotype, to induce nasopharyngeal colonisation for the purpose of vaccine research. The aims are to review comprehensively the safety profile of EHPC, explore the association between pneumococcal colonisation and frequency of safety review and describe the medical intervention required to undertake such studies.Methods:A single-centre review of all EHPC studies performed 2011–2021. All recorded serious adverse events (SAE) in eligible studies are reported. An unblinded meta-analysis of collated anonymised individual patient data from eligible EHPC studies was undertaken to assess the association between experimental pneumococcal colonisation and the frequency of safety events following inoculation.Results:In 1416 individuals (median age 21, IQR 20–25), 1663 experimental pneumococcal inoculations were performed. No pneumococcal-related SAE have occurred. 214 safety review events were identified with 182 (12.85%) participants presenting with symptoms potentially in keeping with pneumococcal infection, predominantly in pneumococcal colonised individuals (colonised = 96/658, non-colonised = 86/1005, OR 1.81 (95% CI 1.28–2.56, P = <0.001). The majority were mild (pneumococcal group = 72.7% [120/165 reported symptoms], non-pneumococcal = 86.7% [124/143 reported symptoms]). 1.6% (23/1416) required antibiotics for safety.Discussion:No SAEs were identified directly relating to pneumococcal inoculation. Safety review for symptoms was infrequent but occurred more in experimentally colonised participants. Most symptoms were mild and resolved with conservative management. A small minority required antibiotics, notably those serotype 3 inoculated.Conclusion:Outpatient human pneumococcal challenge can be conducted safely with appropriate levels of safety monitoring procedures in place.

AB - Introduction:Experimental Human Pneumococcal Challenge (EHPC) involves the controlled exposure of adults to a specific antibiotic-sensitive Streptococcus pneumoniae serotype, to induce nasopharyngeal colonisation for the purpose of vaccine research. The aims are to review comprehensively the safety profile of EHPC, explore the association between pneumococcal colonisation and frequency of safety review and describe the medical intervention required to undertake such studies.Methods:A single-centre review of all EHPC studies performed 2011–2021. All recorded serious adverse events (SAE) in eligible studies are reported. An unblinded meta-analysis of collated anonymised individual patient data from eligible EHPC studies was undertaken to assess the association between experimental pneumococcal colonisation and the frequency of safety events following inoculation.Results:In 1416 individuals (median age 21, IQR 20–25), 1663 experimental pneumococcal inoculations were performed. No pneumococcal-related SAE have occurred. 214 safety review events were identified with 182 (12.85%) participants presenting with symptoms potentially in keeping with pneumococcal infection, predominantly in pneumococcal colonised individuals (colonised = 96/658, non-colonised = 86/1005, OR 1.81 (95% CI 1.28–2.56, P = <0.001). The majority were mild (pneumococcal group = 72.7% [120/165 reported symptoms], non-pneumococcal = 86.7% [124/143 reported symptoms]). 1.6% (23/1416) required antibiotics for safety.Discussion:No SAEs were identified directly relating to pneumococcal inoculation. Safety review for symptoms was infrequent but occurred more in experimentally colonised participants. Most symptoms were mild and resolved with conservative management. A small minority required antibiotics, notably those serotype 3 inoculated.Conclusion:Outpatient human pneumococcal challenge can be conducted safely with appropriate levels of safety monitoring procedures in place.

U2 - 10.1371/journal.pone.0284399

DO - 10.1371/journal.pone.0284399

M3 - Article

VL - 18

SP - e0284399

JO - PLoS ONE

JF - PLoS ONE

IS - 5 May

M1 - e0284399

ER -

Comprehensive review of safety in Experimental Human Pneumococcal Challenge

Abstract

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Safety, Diagnostics, and Serotype Expansion in a Human Pneumococcal Challenge Model Involving Healthy Participants

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