Heterologous prime-boost vaccination with viral vectors simian adenovirus 63 (ChAd63) and Modified Vaccinia Ankara (MVA) induces potent T cell and antibody responses in humans. The 8-week regimen demonstrates significant efficacy against malaria when expressing the pre-erythrocytic malaria antigen Thrombospondin-Related Adhesion Protein fused to a multiple epitope string (ME-TRAP). We tested these vaccines in 7 new 4- and 8-week interval schedules to evaluate safety and immunogenicity of multiple ChAd63 ME-TRAP priming vaccinations (denoted A), multiple MVA ME-TRAP boosts (denoted M) and alternating vectors. All regimens exhibited acceptable reactogenicity and CD8(+) T cell immunogenicity was enhanced with a 4-week interval (AM) and with incorporation of additional ChAd63 ME-TRAP vaccination at 4- or 8-weeks (AAM or A_ A_ M). Induction of TRAP antibodies was comparable between schedules. T cell immunity against the ChAd63 hexon did not affect T cell responses to the vaccine insert, however pre-vaccination ChAd63-specific T cells correlated with reduced TRAP antibodies. Vaccine-induced antibodies against MVA did not affect TRAP antibody induction, and correlated positively with ME-TRAP-specific T cells. This study identifies potentially more effective immunisation regimens to assess in Phase IIa trials and demonstrates a degree of flexibility with the timing of vectored vaccine administration, aiding incorporation into existing vaccination programmes.

Assessment of novel vaccination regimens using viral vectored liver stage malaria vaccines encoding ME-TRAP / Bliss, Carly M.; Bowyer, Georgina; Anagnostou, Nicholas A.; Havelock, Tom; Snudden, Claudia M.; Davies, Huw; De Cassan, Simone C.; Grobbelaar, Amy; Lawrie, Alison M.; Venkatraman, Navin; Poulton, Ian D.; Roberts, Rachel; Mange, Pooja B.; Choudhary, Prateek; Faust, Saul N.; Colloca, Stefano; Gilbert, Sarah C.; Nicosia, Alfredo; Hill, Adrian V. S.; Ewer, Katie J.. - In: SCIENTIFIC REPORTS. - ISSN 2045-2322. - 8:1(2018), p. 3390. [10.1038/s41598-018-21630-4]

Assessment of novel vaccination regimens using viral vectored liver stage malaria vaccines encoding ME-TRAP

Nicosia, Alfredo;
2018

Abstract

Heterologous prime-boost vaccination with viral vectors simian adenovirus 63 (ChAd63) and Modified Vaccinia Ankara (MVA) induces potent T cell and antibody responses in humans. The 8-week regimen demonstrates significant efficacy against malaria when expressing the pre-erythrocytic malaria antigen Thrombospondin-Related Adhesion Protein fused to a multiple epitope string (ME-TRAP). We tested these vaccines in 7 new 4- and 8-week interval schedules to evaluate safety and immunogenicity of multiple ChAd63 ME-TRAP priming vaccinations (denoted A), multiple MVA ME-TRAP boosts (denoted M) and alternating vectors. All regimens exhibited acceptable reactogenicity and CD8(+) T cell immunogenicity was enhanced with a 4-week interval (AM) and with incorporation of additional ChAd63 ME-TRAP vaccination at 4- or 8-weeks (AAM or A_ A_ M). Induction of TRAP antibodies was comparable between schedules. T cell immunity against the ChAd63 hexon did not affect T cell responses to the vaccine insert, however pre-vaccination ChAd63-specific T cells correlated with reduced TRAP antibodies. Vaccine-induced antibodies against MVA did not affect TRAP antibody induction, and correlated positively with ME-TRAP-specific T cells. This study identifies potentially more effective immunisation regimens to assess in Phase IIa trials and demonstrates a degree of flexibility with the timing of vectored vaccine administration, aiding incorporation into existing vaccination programmes.
2018
Assessment of novel vaccination regimens using viral vectored liver stage malaria vaccines encoding ME-TRAP / Bliss, Carly M.; Bowyer, Georgina; Anagnostou, Nicholas A.; Havelock, Tom; Snudden, Claudia M.; Davies, Huw; De Cassan, Simone C.; Grobbelaar, Amy; Lawrie, Alison M.; Venkatraman, Navin; Poulton, Ian D.; Roberts, Rachel; Mange, Pooja B.; Choudhary, Prateek; Faust, Saul N.; Colloca, Stefano; Gilbert, Sarah C.; Nicosia, Alfredo; Hill, Adrian V. S.; Ewer, Katie J.. - In: SCIENTIFIC REPORTS. - ISSN 2045-2322. - 8:1(2018), p. 3390. [10.1038/s41598-018-21630-4]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/745338
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