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<jats:title>ABSTRACT</jats:title> <jats:p>Despite promising progress in malaria vaccine development in recent years, an efficacious subunit vaccine against <jats:named-content content-type="genus-species">Plasmodium falciparum</jats:named-content> remains to be licensed and deployed. Cell-mediated protection from liver-stage malaria relies on a sufficient number of antigen-specific T cells reaching the liver during the time that parasites are present. A single vaccine expressing two antigens could potentially increase both the size and breadth of the antigen-specific response while halving vaccine production costs. In this study, we investigated combining two liver-stage antigens, <jats:named-content content-type="genus-species">P. falciparum</jats:named-content> LSA1 (PfLSA1) and PfLSAP2, and investigated the induction of protective efficacy by coadministration of single-antigen vectors or vaccination with dual-antigen vectors, using simian adenovirus and modified vaccinia virus Ankara vectors. The efficacy of these vaccines was assessed in mouse malaria challenge models using chimeric <jats:named-content content-type="genus-species">P. berghei</jats:named-content> parasites expressing the relevant <jats:named-content content-type="genus-species">P. falciparum</jats:named-content> antigens and challenging mice at the peak of the T cell response. Vaccination with a combination of the single-antigen vectors expressing PfLSA1 or PfLSAP2 was shown to improve protective efficacy compared to vaccination with each single-antigen vector alone. Vaccination with dual-antigen vectors expressing both PfLSA1 and PfLSAP2 resulted in responses to both antigens, particularly in outbred mice, and most importantly, the efficacy was equivalent to that of vaccination with a mixture of single-antigen vectors. Based on these promising data, dual-antigen vectors expressing PfLSA1 and PfLSAP2 will now proceed to manufacturing and clinical assessment under good manufacturing practice (GMP) guidelines.</jats:p>

Original publication

DOI

10.1128/iai.00573-19

Type

Journal article

Journal

Infection and Immunity

Publisher

American Society for Microbiology

Publication Date

18/11/2019

Volume

88