A phase I trial evaluating the safety and immunogenicity of a candidate tuberculosis vaccination regimen, ChAdOx1 85A prime - MVA85A boost in healthy UK adults

Morven Wilkie; Iman Satti; Alice Minhinnick; Stephanie Harris; Michael Riste; Raquel Lopez Ramon; Sharon Sheehan; Zita-Rose Manjaly Thomas; Daniel Wright; Lisa Stockdale; Ali Hamidi; Matthew K O'Shea; Kritica Dwivedi; Hannah Michaela Behrens; Tamara Davenne; Joshua Morton; Samantha Vermaak; Alison Lawrie; Paul Moss; Helen McShane

doi:10.1016/j.vaccine.2019.10.102

A phase I trial evaluating the safety and immunogenicity of a candidate tuberculosis vaccination regimen, ChAdOx1 85A prime - MVA85A boost in healthy UK adults

Morven Wilkie, Iman Satti, Alice Minhinnick, Stephanie Harris, Michael Riste, Raquel Lopez Ramon, Sharon Sheehan, Zita-Rose Manjaly Thomas, Daniel Wright, Lisa Stockdale, Ali Hamidi, Matthew K O'Shea, Kritica Dwivedi, Hannah Michaela Behrens, Tamara Davenne, Joshua Morton, Samantha Vermaak, Alison Lawrie, Paul Moss, Helen McShane

Medical and Dental Sciences

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

19 Citations (Scopus)

Abstract

BACKGROUND: This phase I trial evaluated the safety and immunogenicity of a candidate tuberculosis vaccination regimen, ChAdOx1 85A prime-MVA85A boost, previously demonstrated to be protective in animal studies, in healthy UK adults.

METHODS: We enrolled 42 healthy, BCG-vaccinated adults into 4 groups: low dose Starter Group (n = 6; ChAdOx1 85A alone), high dose groups; Group A (n = 12; ChAdOx1 85A), Group B (n = 12; ChAdOx1 85A prime - MVA85A boost) or Group C (n = 12; ChAdOx1 85A - ChAdOx1 85A prime - MVA85A boost). Safety was determined by collection of solicited and unsolicited vaccine-related adverse events (AEs). Immunogenicity was measured by antigen-specific ex-vivo IFN-γ ELISpot, IgG serum ELISA, and antigen-specific intracellular IFN-γ, TNF-α, IL-2 and IL-17.

RESULTS: AEs were mostly mild/moderate, with no Serious Adverse Events. ChAdOx1 85A induced Ag85A-specific ELISpot and intracellular cytokine CD4+ and CD8+ T cell responses, which were not boosted by a second dose, but were boosted with MVA85A. Polyfunctional CD4+ T cells (IFN-γ, TNF-α and IL-2) and IFN-γ+, TNF-α+ CD8+ T cells were induced by ChAdOx1 85A and boosted by MVA85A. ChAdOx1 85A induced serum Ag85A IgG responses which were boosted by MVA85A.

CONCLUSION: A ChAdOx1 85A prime - MVA85A boost is well tolerated and immunogenic in healthy UK adults.

Original language	English
Pages (from-to)	779-789
Number of pages	11
Journal	Vaccine
Volume	38
Issue number	4
DOIs	https://doi.org/10.1016/j.vaccine.2019.10.102
Publication status	Published - 22 Jan 2020

Bibliographical note

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.vaccine.2019.10.102

Cite this

Wilkie, M., Satti, I., Minhinnick, A., Harris, S., Riste, M., Ramon, R. L., Sheehan, S., Thomas, Z-R. M., Wright, D., Stockdale, L., Hamidi, A., O'Shea, M. K., Dwivedi, K., Behrens, H. M., Davenne, T., Morton, J., Vermaak, S., Lawrie, A., Moss, P., & McShane, H. (2020). A phase I trial evaluating the safety and immunogenicity of a candidate tuberculosis vaccination regimen, ChAdOx1 85A prime - MVA85A boost in healthy UK adults. Vaccine, 38(4), 779-789. https://doi.org/10.1016/j.vaccine.2019.10.102

@article{6634699f08af4deca22d40d2ea69db5a,

title = "A phase I trial evaluating the safety and immunogenicity of a candidate tuberculosis vaccination regimen, ChAdOx1 85A prime - MVA85A boost in healthy UK adults",

abstract = "BACKGROUND: This phase I trial evaluated the safety and immunogenicity of a candidate tuberculosis vaccination regimen, ChAdOx1 85A prime-MVA85A boost, previously demonstrated to be protective in animal studies, in healthy UK adults.METHODS: We enrolled 42 healthy, BCG-vaccinated adults into 4 groups: low dose Starter Group (n = 6; ChAdOx1 85A alone), high dose groups; Group A (n = 12; ChAdOx1 85A), Group B (n = 12; ChAdOx1 85A prime - MVA85A boost) or Group C (n = 12; ChAdOx1 85A - ChAdOx1 85A prime - MVA85A boost). Safety was determined by collection of solicited and unsolicited vaccine-related adverse events (AEs). Immunogenicity was measured by antigen-specific ex-vivo IFN-γ ELISpot, IgG serum ELISA, and antigen-specific intracellular IFN-γ, TNF-α, IL-2 and IL-17.RESULTS: AEs were mostly mild/moderate, with no Serious Adverse Events. ChAdOx1 85A induced Ag85A-specific ELISpot and intracellular cytokine CD4+ and CD8+ T cell responses, which were not boosted by a second dose, but were boosted with MVA85A. Polyfunctional CD4+ T cells (IFN-γ, TNF-α and IL-2) and IFN-γ+, TNF-α+ CD8+ T cells were induced by ChAdOx1 85A and boosted by MVA85A. ChAdOx1 85A induced serum Ag85A IgG responses which were boosted by MVA85A.CONCLUSION: A ChAdOx1 85A prime - MVA85A boost is well tolerated and immunogenic in healthy UK adults.",

author = "Morven Wilkie and Iman Satti and Alice Minhinnick and Stephanie Harris and Michael Riste and Ramon, {Raquel Lopez} and Sharon Sheehan and Thomas, {Zita-Rose Manjaly} and Daniel Wright and Lisa Stockdale and Ali Hamidi and O'Shea, {Matthew K} and Kritica Dwivedi and Behrens, {Hannah Michaela} and Tamara Davenne and Joshua Morton and Samantha Vermaak and Alison Lawrie and Paul Moss and Helen McShane",

year = "2020",

month = jan,

day = "22",

doi = "10.1016/j.vaccine.2019.10.102",

language = "English",

volume = "38",

pages = "779--789",

journal = "Vaccine",

issn = "0264-410X",

publisher = "Elsevier",

number = "4",

}

Wilkie, M, Satti, I, Minhinnick, A, Harris, S, Riste, M, Ramon, RL, Sheehan, S, Thomas, Z-RM, Wright, D, Stockdale, L, Hamidi, A, O'Shea, MK, Dwivedi, K, Behrens, HM, Davenne, T, Morton, J, Vermaak, S, Lawrie, A, Moss, P & McShane, H 2020, 'A phase I trial evaluating the safety and immunogenicity of a candidate tuberculosis vaccination regimen, ChAdOx1 85A prime - MVA85A boost in healthy UK adults', Vaccine, vol. 38, no. 4, pp. 779-789. https://doi.org/10.1016/j.vaccine.2019.10.102

TY - JOUR

T1 - A phase I trial evaluating the safety and immunogenicity of a candidate tuberculosis vaccination regimen, ChAdOx1 85A prime - MVA85A boost in healthy UK adults

AU - Wilkie, Morven

AU - Satti, Iman

AU - Minhinnick, Alice

AU - Harris, Stephanie

AU - Riste, Michael

AU - Ramon, Raquel Lopez

AU - Sheehan, Sharon

AU - Thomas, Zita-Rose Manjaly

AU - Wright, Daniel

AU - Stockdale, Lisa

AU - Hamidi, Ali

AU - O'Shea, Matthew K

AU - Dwivedi, Kritica

AU - Behrens, Hannah Michaela

AU - Davenne, Tamara

AU - Morton, Joshua

AU - Vermaak, Samantha

AU - Lawrie, Alison

AU - Moss, Paul

AU - McShane, Helen

PY - 2020/1/22

Y1 - 2020/1/22

N2 - BACKGROUND: This phase I trial evaluated the safety and immunogenicity of a candidate tuberculosis vaccination regimen, ChAdOx1 85A prime-MVA85A boost, previously demonstrated to be protective in animal studies, in healthy UK adults.METHODS: We enrolled 42 healthy, BCG-vaccinated adults into 4 groups: low dose Starter Group (n = 6; ChAdOx1 85A alone), high dose groups; Group A (n = 12; ChAdOx1 85A), Group B (n = 12; ChAdOx1 85A prime - MVA85A boost) or Group C (n = 12; ChAdOx1 85A - ChAdOx1 85A prime - MVA85A boost). Safety was determined by collection of solicited and unsolicited vaccine-related adverse events (AEs). Immunogenicity was measured by antigen-specific ex-vivo IFN-γ ELISpot, IgG serum ELISA, and antigen-specific intracellular IFN-γ, TNF-α, IL-2 and IL-17.RESULTS: AEs were mostly mild/moderate, with no Serious Adverse Events. ChAdOx1 85A induced Ag85A-specific ELISpot and intracellular cytokine CD4+ and CD8+ T cell responses, which were not boosted by a second dose, but were boosted with MVA85A. Polyfunctional CD4+ T cells (IFN-γ, TNF-α and IL-2) and IFN-γ+, TNF-α+ CD8+ T cells were induced by ChAdOx1 85A and boosted by MVA85A. ChAdOx1 85A induced serum Ag85A IgG responses which were boosted by MVA85A.CONCLUSION: A ChAdOx1 85A prime - MVA85A boost is well tolerated and immunogenic in healthy UK adults.

AB - BACKGROUND: This phase I trial evaluated the safety and immunogenicity of a candidate tuberculosis vaccination regimen, ChAdOx1 85A prime-MVA85A boost, previously demonstrated to be protective in animal studies, in healthy UK adults.METHODS: We enrolled 42 healthy, BCG-vaccinated adults into 4 groups: low dose Starter Group (n = 6; ChAdOx1 85A alone), high dose groups; Group A (n = 12; ChAdOx1 85A), Group B (n = 12; ChAdOx1 85A prime - MVA85A boost) or Group C (n = 12; ChAdOx1 85A - ChAdOx1 85A prime - MVA85A boost). Safety was determined by collection of solicited and unsolicited vaccine-related adverse events (AEs). Immunogenicity was measured by antigen-specific ex-vivo IFN-γ ELISpot, IgG serum ELISA, and antigen-specific intracellular IFN-γ, TNF-α, IL-2 and IL-17.RESULTS: AEs were mostly mild/moderate, with no Serious Adverse Events. ChAdOx1 85A induced Ag85A-specific ELISpot and intracellular cytokine CD4+ and CD8+ T cell responses, which were not boosted by a second dose, but were boosted with MVA85A. Polyfunctional CD4+ T cells (IFN-γ, TNF-α and IL-2) and IFN-γ+, TNF-α+ CD8+ T cells were induced by ChAdOx1 85A and boosted by MVA85A. ChAdOx1 85A induced serum Ag85A IgG responses which were boosted by MVA85A.CONCLUSION: A ChAdOx1 85A prime - MVA85A boost is well tolerated and immunogenic in healthy UK adults.

UR - http://www.scopus.com/inward/record.url?scp=85075435347&partnerID=8YFLogxK

U2 - 10.1016/j.vaccine.2019.10.102

DO - 10.1016/j.vaccine.2019.10.102

M3 - Article

C2 - 31735500

SN - 0264-410X

VL - 38

SP - 779

EP - 789

JO - Vaccine

JF - Vaccine

IS - 4

ER -

A phase I trial evaluating the safety and immunogenicity of a candidate tuberculosis vaccination regimen, ChAdOx1 85A prime - MVA85A boost in healthy UK adults

Abstract

Bibliographical note

UN SDGs

Access to Document

Fingerprint

Cite this