Pfs230 and Pfs48/45 fusion proteins elicit strong transmission-blocking antibody responses against Plasmodium falciparum

TY - JOUR

T1 - Pfs230 and Pfs48/45 fusion proteins elicit strong transmission-blocking antibody responses against Plasmodium falciparum

AU - Singh, Susheel K

AU - Thrane, Susan

AU - Chourasia, Bishwanath K

AU - Teelen, Karina

AU - Graumans, Wouter

AU - Stoter, Rianne

AU - van Gemert, Geert-Jan

AU - van de Vegte-Bolmer, Marga G

AU - Nielsen, Morten A

AU - Salanti, Ali

AU - Sander, Adam F

AU - Sauerwein, Robert W

AU - Jore, Matthijs M

AU - Theisen, Michael

PY - 2019

Y1 - 2019

N2 - The Plasmodium falciparum Pfs230 and Pfs48/45 proteins are expressed during transmission from man to mosquito and are leading candidates for a malaria transmission blocking vaccine. Individually they generate transmission blocking (TB) antibodies in rodent models. Whether the single protein vaccines are suitable to use in field settings will primarily depend on their potency to elicit functional antibodies. We hypothesized that a combination of both proteins will be more potent than each protein individually. Therefore we designed chimeric proteins composed of fragments of both Pfs230 and Pfs48/45 as well as single protein fragments, and expressed these in Lactoccus lactis. Both the individual Pfs230 and Pfs48/45 fragments and chimeras elicited high levels of functional antibodies in mice. Importantly, one of the chimeric proteins elicited over threefold higher transmission blocking antibody responses than the single antigens alone. Furthermore the immunogenicity of one of the chimeras could be enhanced through coupling to a virus-like particle (VLP). Altogether these data support further clinical development of these novel constructs.

AB - The Plasmodium falciparum Pfs230 and Pfs48/45 proteins are expressed during transmission from man to mosquito and are leading candidates for a malaria transmission blocking vaccine. Individually they generate transmission blocking (TB) antibodies in rodent models. Whether the single protein vaccines are suitable to use in field settings will primarily depend on their potency to elicit functional antibodies. We hypothesized that a combination of both proteins will be more potent than each protein individually. Therefore we designed chimeric proteins composed of fragments of both Pfs230 and Pfs48/45 as well as single protein fragments, and expressed these in Lactoccus lactis. Both the individual Pfs230 and Pfs48/45 fragments and chimeras elicited high levels of functional antibodies in mice. Importantly, one of the chimeric proteins elicited over threefold higher transmission blocking antibody responses than the single antigens alone. Furthermore the immunogenicity of one of the chimeras could be enhanced through coupling to a virus-like particle (VLP). Altogether these data support further clinical development of these novel constructs.

U2 - 10.3389/fimmu.2019.01256

DO - 10.3389/fimmu.2019.01256

M3 - Journal article

C2 - 31231386

SN - 1664-3224

VL - 10

SP - 1256

JO - Frontiers in Immunology

JF - Frontiers in Immunology

ER -