A viral vectored prime-boost immunization regime targeting the malaria pfs25 antigen induces transmission-blocking activity
Author(s)
Type
Journal Article
Abstract
The ookinete surface protein Pfs25 is a macrogamete-to-ookinete/ookinete stage antigen of Plasmodium falciparum,
capable of exerting high-level anti-malarial transmission-blocking activity following immunization with recombinant
protein-in-adjuvant formulations. Here, this antigen was expressed in recombinant chimpanzee adenovirus 63 (ChAd63),
human adenovirus serotype 5 (AdHu5) and modified vaccinia virus Ankara (MVA) viral vectored vaccines. Two
immunizations were administered to mice in a heterologous prime-boost regime. Immunization of mice with AdHu5
Pfs25 at week 0 and MVA Pfs25 at week 10 (Ad-MVA Pfs25) resulted in high anti-Pfs25 IgG titers, consisting of predominantly
isotypes IgG1 and IgG2a. A single priming immunization with ChAd63 Pfs25 was as effective as AdHu5 Pfs25 with respect to
ELISA titers at 8 weeks post-immunization. Sera from Ad-MVA Pfs25 immunized mice inhibited the transmission of P.
falciparum to the mosquito both ex vivo and in vivo. In a standard membrane-feeding assay using NF54 strain P. falciparum,
oocyst intensity in Anopheles stephensi mosquitoes was significantly reduced in an IgG concentration-dependent manner
when compared to control feeds (96% reduction of intensity, 78% reduction in prevalence at a 1 in 5 dilution of sera). In
addition, an in vivo transmission-blocking effect was also demonstrated by direct feeding of immunized mice infected with
Pfs25DR3, a chimeric P. berghei line expressing Pfs25 in place of endogenous Pbs25. In this assay the density of Pfs25DR3
oocysts was significantly reduced when mosquitoes were fed on vaccinated as compared to control mice (67% reduction of
intensity, 28% reduction in prevalence) and specific IgG titer correlated with efficacy. These data confirm the utility of the
adenovirus-MVA vaccine platform for the induction of antibodies with transmission-blocking activity, and support the
continued development of this alternative approach to transmission-blocking malaria subunit vaccines.
capable of exerting high-level anti-malarial transmission-blocking activity following immunization with recombinant
protein-in-adjuvant formulations. Here, this antigen was expressed in recombinant chimpanzee adenovirus 63 (ChAd63),
human adenovirus serotype 5 (AdHu5) and modified vaccinia virus Ankara (MVA) viral vectored vaccines. Two
immunizations were administered to mice in a heterologous prime-boost regime. Immunization of mice with AdHu5
Pfs25 at week 0 and MVA Pfs25 at week 10 (Ad-MVA Pfs25) resulted in high anti-Pfs25 IgG titers, consisting of predominantly
isotypes IgG1 and IgG2a. A single priming immunization with ChAd63 Pfs25 was as effective as AdHu5 Pfs25 with respect to
ELISA titers at 8 weeks post-immunization. Sera from Ad-MVA Pfs25 immunized mice inhibited the transmission of P.
falciparum to the mosquito both ex vivo and in vivo. In a standard membrane-feeding assay using NF54 strain P. falciparum,
oocyst intensity in Anopheles stephensi mosquitoes was significantly reduced in an IgG concentration-dependent manner
when compared to control feeds (96% reduction of intensity, 78% reduction in prevalence at a 1 in 5 dilution of sera). In
addition, an in vivo transmission-blocking effect was also demonstrated by direct feeding of immunized mice infected with
Pfs25DR3, a chimeric P. berghei line expressing Pfs25 in place of endogenous Pbs25. In this assay the density of Pfs25DR3
oocysts was significantly reduced when mosquitoes were fed on vaccinated as compared to control mice (67% reduction of
intensity, 28% reduction in prevalence) and specific IgG titer correlated with efficacy. These data confirm the utility of the
adenovirus-MVA vaccine platform for the induction of antibodies with transmission-blocking activity, and support the
continued development of this alternative approach to transmission-blocking malaria subunit vaccines.
Date Issued
2011-12-28
Date Acceptance
2011-11-29
Citation
PLOS One, 2011, 6 (12)
ISSN
1932-6203
Publisher
Public Library of Science
Journal / Book Title
PLOS One
Volume
6
Issue
12
Copyright Statement
© 2011 Goodman et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Subjects
Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
MULTIDISCIPLINARY SCIENCES
SUBUNIT VACCINE IMMUNOGENICITY
MEROZOITE SURFACE PROTEIN-1
PLASMODIUM-FALCIPARUM
FUNCTIONAL IMMUNOGENICITY
ADJUVANT VACCINES
SEXUAL STAGE
IN-VITRO
ANTIBODIES
CANDIDATE
IMMUNITY
Animals
Anopheles
Antigens, Protozoan
Base Sequence
Blotting, Western
DNA Primers
Enzyme-Linked Immunosorbent Assay
Fluorescent Antibody Technique
Genetic Vectors
Malaria, Falciparum
Mice
Plasmodium falciparum
Vaccinia virus
General Science & Technology
MD Multidisciplinary
Publication Status
Published
Article Number
e29428