Effective induction of high-titer antibodies by viral vector vaccines

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Abstract

Protein-in-adjuvant vaccines have shown limited success against difficult diseases such as blood-stage malaria. Here we show that a recombinant adenovirus–poxvirus prime-boost immunization regime (known to induce strong T cell immunogenicity) can also induce very strong antigen-specific antibody responses, and we identify a simple complement-based adjuvant to further enhance immunogenicity. Antibodies induced against a blood-stage malaria antigen by this viral vector platform are highly effective against Plasmodium yoelii parasites in mice and against Plasmodium falciparum in vitro.

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Figure 1: AdM42 vaccine–induced immune responses and protection against blood-stage P. yoelii are dependent on the prime-boost interval in BALB/c mice.
Figure 2: AdM42-C4bp vaccine–induced immune responses and protection against blood-stage P. yoelii.

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Acknowledgements

We thank L. Andrews, R. Fredslund-Andersen, J. Furze, C. Hutchings, A. Reyes-Sandoval, A. Spencer, S. Saurya, S. Sridhar, M. Tunnicliff, J.-B. Marchand, S. Moretz and H. Zhou for assistance and S. Ogun for discussions. This work was funded by the UK Medical Research Council and Wellcome Trust. The PATH Malaria Vaccine Initiative program and the Intramural US National Institute of Allergy and Infectious Diseases Program supported the GIA work. S.J.D. held a UK Medical Research Council Studentship during most of this work and is now a Junior Research Fellow of Merton College, Oxford. A.V.S.H. is a Wellcome Trust Principal Research Fellow.

Author information

S.J.D. designed and made the viruses, performed the in vivo experiments and wrote the manuscript. A.C.M. supervised the in vivo experiments. A.L.G. assisted with the GIA experiment. C.A.L. performed the GIA assay and standardized the ELISA. A.A.H. advised on the design of the PfM128 vaccine construct. S.C.G. supervised the design of the viruses. F.H. identified the adjuvant effect of mC4bp for protein vaccines and provided the MSP-142–C4bp construct. A.V.S.H. supervised the experiments and contributed to the manuscript.

Correspondence to Simon J Draper.

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Competing interests

F.H. is an employee of Imaxio, which owns rights to and is developing the C4bp adjuvant technology.

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Supplementary Table 1, Supplementary Fig.1 and Supplementary Methods (PDF 138 kb)

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