New adenovirus-based vaccine vectors targeting Pfs25 elicit antibodies that inhibit Plasmodium falciparum transmission

Abstract Background An effective malaria transmission-blocking vaccine (TBV) would be a major advance in the current efforts to eliminate and, ultimately, eradicate malaria. Antibodies against Plasmodium falciparum surface protein, Pfs25, are known to block parasite development in the mosquito vecto...

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Main Authors: Kathleen A. McGuire, Kazutoyo Miura, Christopher M. Wiethoff, Kim C. Williamson
Format: Article
Language:English
Published: BMC 2017-06-01
Series:Malaria Journal
Subjects:
Online Access:http://link.springer.com/article/10.1186/s12936-017-1896-7
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spelling doaj-122acf55372c4bb68b2e9e6c9bae021d2020-11-24T21:04:33ZengBMCMalaria Journal1475-28752017-06-0116111210.1186/s12936-017-1896-7New adenovirus-based vaccine vectors targeting Pfs25 elicit antibodies that inhibit Plasmodium falciparum transmissionKathleen A. McGuire0Kazutoyo Miura1Christopher M. Wiethoff2Kim C. Williamson3Department of Microbiology and Immunology, Stritch School of Medicine, Loyola University ChicagoLaboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of HealthDepartment of Microbiology and Immunology, Stritch School of Medicine, Loyola University ChicagoDepartment of Microbiology and Immunology, Uniformed Services UniversityAbstract Background An effective malaria transmission-blocking vaccine (TBV) would be a major advance in the current efforts to eliminate and, ultimately, eradicate malaria. Antibodies against Plasmodium falciparum surface protein, Pfs25, are known to block parasite development in the mosquito vector. However, in initial clinical trials the limited immunogenicity of recombinant Pfs25 protein-in-adjuvant vaccines has been a challenge. Methods Novel human adenovirus type 5 (Ad5) vectors were used in heterologous prime boost vaccination strategies to augment the immune response against Pfs25. Specifically, an Ad5 vector that directs expression of full-length, membrane-bound Pfs25 was used as a priming immunization followed by a boost with Ad5 viral particles displaying only the Pfs25 epitope targeted by transmission-blocking antibodies 4B7 and 1D2 (Pfs25 aa 122–134) in hypervariable region 5 of the hexon capsid protein. Results This heterologous prime-boost vaccine strategy induced antibodies that significantly inhibit P. falciparum transmission to mosquitoes in a standard membrane-feeding assay. Further, immunized mice generated a robust anti-Pfs25 antibody response characterized by higher titer, higher relative avidity and a broader IgG subclass profile than observed with a homologous prime-boost with recombinant Pfs25/alum. Conclusion The data suggest that focusing the immune response against defined epitopes displayed on the viral capsid is an effective strategy for transmission-blocking vaccine development.http://link.springer.com/article/10.1186/s12936-017-1896-7MalariaP. falciparumTransmission-blocking immunityPfs25Adenovirus vaccine vectors
collection DOAJ
language English
format Article
sources DOAJ
author Kathleen A. McGuire
Kazutoyo Miura
Christopher M. Wiethoff
Kim C. Williamson
spellingShingle Kathleen A. McGuire
Kazutoyo Miura
Christopher M. Wiethoff
Kim C. Williamson
New adenovirus-based vaccine vectors targeting Pfs25 elicit antibodies that inhibit Plasmodium falciparum transmission
Malaria Journal
Malaria
P. falciparum
Transmission-blocking immunity
Pfs25
Adenovirus vaccine vectors
author_facet Kathleen A. McGuire
Kazutoyo Miura
Christopher M. Wiethoff
Kim C. Williamson
author_sort Kathleen A. McGuire
title New adenovirus-based vaccine vectors targeting Pfs25 elicit antibodies that inhibit Plasmodium falciparum transmission
title_short New adenovirus-based vaccine vectors targeting Pfs25 elicit antibodies that inhibit Plasmodium falciparum transmission
title_full New adenovirus-based vaccine vectors targeting Pfs25 elicit antibodies that inhibit Plasmodium falciparum transmission
title_fullStr New adenovirus-based vaccine vectors targeting Pfs25 elicit antibodies that inhibit Plasmodium falciparum transmission
title_full_unstemmed New adenovirus-based vaccine vectors targeting Pfs25 elicit antibodies that inhibit Plasmodium falciparum transmission
title_sort new adenovirus-based vaccine vectors targeting pfs25 elicit antibodies that inhibit plasmodium falciparum transmission
publisher BMC
series Malaria Journal
issn 1475-2875
publishDate 2017-06-01
description Abstract Background An effective malaria transmission-blocking vaccine (TBV) would be a major advance in the current efforts to eliminate and, ultimately, eradicate malaria. Antibodies against Plasmodium falciparum surface protein, Pfs25, are known to block parasite development in the mosquito vector. However, in initial clinical trials the limited immunogenicity of recombinant Pfs25 protein-in-adjuvant vaccines has been a challenge. Methods Novel human adenovirus type 5 (Ad5) vectors were used in heterologous prime boost vaccination strategies to augment the immune response against Pfs25. Specifically, an Ad5 vector that directs expression of full-length, membrane-bound Pfs25 was used as a priming immunization followed by a boost with Ad5 viral particles displaying only the Pfs25 epitope targeted by transmission-blocking antibodies 4B7 and 1D2 (Pfs25 aa 122–134) in hypervariable region 5 of the hexon capsid protein. Results This heterologous prime-boost vaccine strategy induced antibodies that significantly inhibit P. falciparum transmission to mosquitoes in a standard membrane-feeding assay. Further, immunized mice generated a robust anti-Pfs25 antibody response characterized by higher titer, higher relative avidity and a broader IgG subclass profile than observed with a homologous prime-boost with recombinant Pfs25/alum. Conclusion The data suggest that focusing the immune response against defined epitopes displayed on the viral capsid is an effective strategy for transmission-blocking vaccine development.
topic Malaria
P. falciparum
Transmission-blocking immunity
Pfs25
Adenovirus vaccine vectors
url http://link.springer.com/article/10.1186/s12936-017-1896-7
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