Safety and immunogenicity of an FP9-vectored candidate tuberculosis vaccine (FP85A), alone and with candidate vaccine MVA85A in BCG-vaccinated healthy adults: A phase i clinical trial

Rosalind Rowland, Ansar A. Pathan, Iman Satti, Ian D. Poulton, Magali M.L. Matsumiya, Megan Whittaker, Angela M. Minassian, Geraldine A. O'Hara, Matthew Hamill, Janet T. Scott, Stephanie A. Harris, Hazel C. Poyntz, Cynthia Bateman, Joel Meyer, Nicola Williams, Sarah C. Gilbert, Alison M. Lawrie, Adrian V.S. Hill, Helen McShane

Research output: Contribution to journalArticle

Abstract

The safety and immunogenicity of a new candidate tuberculosis (TB) vaccine, FP85A was evaluated alone and in heterologous prime-boost regimes with another candidate TB vaccine, MVA85A. This was an open label, non-controlled, non-randomized Phase I clinical trial. Healthy previously BCG-vaccinated adult subjects were enrolled sequentially into three groups and vaccinated with FP85A alone, or both FP85A and MVA85A, with a four week interval between vaccinations. Passive and active data on adverse events were collected. Immunogenicity was evaluated by Enzyme Linked Immunospot (ELISpot), flow cytometry and Enzyme Linked Immunosorbent assay (ELISA ). Most adverse events were mild and there were no vaccine-related serious adverse events. FP85A vaccination did not enhance antigen 85A-specific cellular immunity. When MVA85A vaccination was preceded by FP85A vaccination, cellular immune responses were lower compared with when MVA85A vaccination was the first immunisation. MVA85A vaccination, but not FP85A vaccination, induced anti-MVA IgG antibodies. Both MVA85A and FP85A vaccinations induced anti-FP9 IgG antibodies. In conclusion, FP85A vaccination was well tolerated but did not induce antigen-specific cellular immune responses. We hypothesize that FP85A induced anti-FP9 IgG antibodies with cross-reactivity for MVA85A, which may have mediated inhibition of the immune response to subsequent MVA85A. ClinicalTrials.gov identification number: NCT00653770.

Original languageEnglish (US)
Pages (from-to)50-62
Number of pages13
JournalHuman Vaccines and Immunotherapeutics
Volume9
Issue number1
DOIs
StatePublished - Jan 1 2013
Externally publishedYes

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Tuberculosis Vaccines
Mycobacterium bovis
Vaccination
Vaccines
Clinical Trials
Safety
Cellular Immunity
Antibodies
MVA 85A
Antigens
Clinical Trials, Phase I
Immunization
Flow Cytometry
Enzyme-Linked Immunosorbent Assay

Keywords

  • Heterologous prime-boost regimes
  • Phase I clinical trial
  • Poxvirus-vectored subunit vaccines
  • Tuberculosis vaccines

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology

Cite this

Safety and immunogenicity of an FP9-vectored candidate tuberculosis vaccine (FP85A), alone and with candidate vaccine MVA85A in BCG-vaccinated healthy adults : A phase i clinical trial. / Rowland, Rosalind; Pathan, Ansar A.; Satti, Iman; Poulton, Ian D.; Matsumiya, Magali M.L.; Whittaker, Megan; Minassian, Angela M.; O'Hara, Geraldine A.; Hamill, Matthew; Scott, Janet T.; Harris, Stephanie A.; Poyntz, Hazel C.; Bateman, Cynthia; Meyer, Joel; Williams, Nicola; Gilbert, Sarah C.; Lawrie, Alison M.; Hill, Adrian V.S.; McShane, Helen.

In: Human Vaccines and Immunotherapeutics, Vol. 9, No. 1, 01.01.2013, p. 50-62.

Research output: Contribution to journalArticle

Rowland, R, Pathan, AA, Satti, I, Poulton, ID, Matsumiya, MML, Whittaker, M, Minassian, AM, O'Hara, GA, Hamill, M, Scott, JT, Harris, SA, Poyntz, HC, Bateman, C, Meyer, J, Williams, N, Gilbert, SC, Lawrie, AM, Hill, AVS & McShane, H 2013, 'Safety and immunogenicity of an FP9-vectored candidate tuberculosis vaccine (FP85A), alone and with candidate vaccine MVA85A in BCG-vaccinated healthy adults: A phase i clinical trial', Human Vaccines and Immunotherapeutics, vol. 9, no. 1, pp. 50-62. https://doi.org/10.4161/hv.22464
Rowland, Rosalind ; Pathan, Ansar A. ; Satti, Iman ; Poulton, Ian D. ; Matsumiya, Magali M.L. ; Whittaker, Megan ; Minassian, Angela M. ; O'Hara, Geraldine A. ; Hamill, Matthew ; Scott, Janet T. ; Harris, Stephanie A. ; Poyntz, Hazel C. ; Bateman, Cynthia ; Meyer, Joel ; Williams, Nicola ; Gilbert, Sarah C. ; Lawrie, Alison M. ; Hill, Adrian V.S. ; McShane, Helen. / Safety and immunogenicity of an FP9-vectored candidate tuberculosis vaccine (FP85A), alone and with candidate vaccine MVA85A in BCG-vaccinated healthy adults : A phase i clinical trial. In: Human Vaccines and Immunotherapeutics. 2013 ; Vol. 9, No. 1. pp. 50-62.
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AU - Pathan, Ansar A.

AU - Satti, Iman

AU - Poulton, Ian D.

AU - Matsumiya, Magali M.L.

AU - Whittaker, Megan

AU - Minassian, Angela M.

AU - O'Hara, Geraldine A.

AU - Hamill, Matthew

AU - Scott, Janet T.

AU - Harris, Stephanie A.

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AU - Bateman, Cynthia

AU - Meyer, Joel

AU - Williams, Nicola

AU - Gilbert, Sarah C.

AU - Lawrie, Alison M.

AU - Hill, Adrian V.S.

AU - McShane, Helen

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N2 - The safety and immunogenicity of a new candidate tuberculosis (TB) vaccine, FP85A was evaluated alone and in heterologous prime-boost regimes with another candidate TB vaccine, MVA85A. This was an open label, non-controlled, non-randomized Phase I clinical trial. Healthy previously BCG-vaccinated adult subjects were enrolled sequentially into three groups and vaccinated with FP85A alone, or both FP85A and MVA85A, with a four week interval between vaccinations. Passive and active data on adverse events were collected. Immunogenicity was evaluated by Enzyme Linked Immunospot (ELISpot), flow cytometry and Enzyme Linked Immunosorbent assay (ELISA ). Most adverse events were mild and there were no vaccine-related serious adverse events. FP85A vaccination did not enhance antigen 85A-specific cellular immunity. When MVA85A vaccination was preceded by FP85A vaccination, cellular immune responses were lower compared with when MVA85A vaccination was the first immunisation. MVA85A vaccination, but not FP85A vaccination, induced anti-MVA IgG antibodies. Both MVA85A and FP85A vaccinations induced anti-FP9 IgG antibodies. In conclusion, FP85A vaccination was well tolerated but did not induce antigen-specific cellular immune responses. We hypothesize that FP85A induced anti-FP9 IgG antibodies with cross-reactivity for MVA85A, which may have mediated inhibition of the immune response to subsequent MVA85A. ClinicalTrials.gov identification number: NCT00653770.

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