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

Scientific Reports
Carly M BlissKatie J Ewer

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 potent...Continue Reading

References

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Citations

Jul 31, 2020·Nature·Neeltje van DoremalenVincent J Munster
Jul 25, 2018·Vaccines·Amy Flaxman, Katie J Ewer
Jun 25, 2019·Frontiers in Immunology·Yun Shan GohLaurent Rénia
Jan 15, 2020·Molecular Therapy. Methods & Clinical Development·Carly M BlissLynda Coughlan
Apr 17, 2021·Frontiers in Immunology·Samantha J PastonLindy G Durrant
May 4, 2021·Frontiers in Molecular Biosciences·Rajashri BezbaruahSaeid Abu-Romman
Aug 6, 2021·Journal of Thrombosis and Haemostasis : JTH·Maha OthmanAlan L Parker

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Methods Mentioned

BETA
flow cytometry
ELISA
blood
Enzyme Linked Immunosorbent Assay
ELISAs

Clinical Trials Mentioned

NCT01364883

Software Mentioned

Gen5
GraphPad Prism
GraphPad

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