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

作者：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

来源：Scientific Reports, 2018, 8(1): 3390.

DOI：10.1038/s41598-018-21630-4

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.

• 出版日期2018-2-21