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Preclinical Development and Assessment of Viral Vectors Expressing a Fusion Antigen of Plasmodium falciparum LSA1 and LSAP2 for Efficacy against Liver-Stage Malaria.
- Source :
-
Infection and immunity [Infect Immun] 2020 Jan 22; Vol. 88 (2). Date of Electronic Publication: 2020 Jan 22 (Print Publication: 2020). - Publication Year :
- 2020
-
Abstract
- Despite promising progress in malaria vaccine development in recent years, an efficacious subunit vaccine against Plasmodium falciparum 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, P. falciparum 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 P. berghei parasites expressing the relevant P. falciparum 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.<br /> (Copyright © 2020 Halbroth et al.)
- Subjects :
- Animals
Antigens, Protozoan genetics
Disease Models, Animal
Female
Humans
Immunity, Cellular
Malaria Vaccines administration & dosage
Malaria Vaccines genetics
Mice, Inbred BALB C
Mice, Inbred ICR
Recombinant Fusion Proteins genetics
Treatment Outcome
Vaccines, Subunit administration & dosage
Vaccines, Subunit genetics
Vaccines, Subunit immunology
Vaccines, Synthetic administration & dosage
Vaccines, Synthetic genetics
Vaccines, Synthetic immunology
Adenoviruses, Simian genetics
Antigens, Protozoan immunology
Drug Carriers
Malaria prevention & control
Malaria Vaccines immunology
Recombinant Fusion Proteins immunology
Vaccinia virus genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1098-5522
- Volume :
- 88
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Infection and immunity
- Publication Type :
- Academic Journal
- Accession number :
- 31740525
- Full Text :
- https://doi.org/10.1128/IAI.00573-19