Sporozoite neutralizing antibodies elicited in mice and rhesus macaques immunized with a Plasmodium falciparum repeat peptide conjugated to meningococcal outer membrane protein complex
Antibodies that neutralize infectivity of malaria sporozoites target the central repeat region of the circumsporozoite (CS) protein, which in Plasmodium falciparum is comprised primarily of 30-40 tandem NANP tetramer repeats. We evaluated immunogenicity of an alum-adsorbed (NANP)6 peptide conjugate...
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2012-11-01
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doaj-fb5be210060a46d0ad1c269451f33b942020-11-25T00:17:52ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882012-11-01210.3389/fcimb.2012.0014636258Sporozoite neutralizing antibodies elicited in mice and rhesus macaques immunized with a Plasmodium falciparum repeat peptide conjugated to meningococcal outer membrane protein complexCraig ePrzysiecki0Bob eLucas1Robert eMitchell2Zhiyun eWen3Daniel eCarapau4Xin-Min eWang5Debbie eNahas6Chengwei eWu7Robert eHepler8Elizabeth eOttinger9Jan eter Meulen10David eKaslow11John eShiver12Hui eXu13Elizabeth eNardin14Merck Research LaboratoriesMerck Research LaboratoriesNew York University School of MedicineMerck Research LaboratoriesNew York University School of MedicineMerck Research LaboratoriesMerck Research LaboratoriesMerck Research LaboratoriesMerck Research LaboratoriesMerck Research LaboratoriesMerck Research LaboratoriesMerck Research LaboratoriesMerck Research LaboratoriesMerck Research LaboratoriesNew York University School of MedicineAntibodies that neutralize infectivity of malaria sporozoites target the central repeat region of the circumsporozoite (CS) protein, which in Plasmodium falciparum is comprised primarily of 30-40 tandem NANP tetramer repeats. We evaluated immunogenicity of an alum-adsorbed (NANP)6 peptide conjugated to an outer membrane protein complex (OMPC) derived from Neisseria meningitidis, a carrier protein used in a licensed H. influenzae pediatric vaccine. Mice immunized with alum-adsorbed (NANP)6-OMPC, with or without Iscomatrix© as co-adjuvant, developed high levels of anti-repeat peptide antibody that inhibited in vitro invasion of human hepatoma cells by transgenic P. berghei sporozoites that express P. falciparum CS repeats (PfPb). Inhibition of sporozoite invasion in vitro correlated with in vivo resistance to challenge by the bites of PfPb infected mosquitoes. Challenged mice had > 90% reduction of hepatic stage parasites as measured by real-time PCR, and either sterile immunity, i.e. no detectable blood stage parasites, or delayed prepatent periods which indicate neutralization of a majority, but not all, sporozoites. Rhesus macaques immunized with two doses of (NANP)6-OMPC/MAA formulated with Iscomatrix© developed anti-repeat antibodies that persisted for ~2 years. A third dose of (NANP)6-OMPC/MAA+ Iscomatrix© at that time elicited strong anamnestic antibody responses. Rhesus macaque immune sera obtained post second and third dose of vaccine displayed high levels of sporozoite neutralizing activity in vitro that correlated with presence of high anti-repeat antibody titers. These preclinical studies in mice of different MHC haplotypes and a non-human primate support use of CS peptide-OMPC conjugates as a highly immunogenic platform to evaluate CS protective epitopes. Potential pre-erythrocytic vaccines can be combined with sexual blood stage vaccines as a multi-antigen malaria vaccine to block invasion and transmission of Plasmodium parasiteshttp://journal.frontiersin.org/Journal/10.3389/fcimb.2012.00146/fullMiceSporozoitesVaccineantibodyRhesusP. falciparum |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Craig ePrzysiecki Bob eLucas Robert eMitchell Zhiyun eWen Daniel eCarapau Xin-Min eWang Debbie eNahas Chengwei eWu Robert eHepler Elizabeth eOttinger Jan eter Meulen David eKaslow John eShiver Hui eXu Elizabeth eNardin |
spellingShingle |
Craig ePrzysiecki Bob eLucas Robert eMitchell Zhiyun eWen Daniel eCarapau Xin-Min eWang Debbie eNahas Chengwei eWu Robert eHepler Elizabeth eOttinger Jan eter Meulen David eKaslow John eShiver Hui eXu Elizabeth eNardin Sporozoite neutralizing antibodies elicited in mice and rhesus macaques immunized with a Plasmodium falciparum repeat peptide conjugated to meningococcal outer membrane protein complex Frontiers in Cellular and Infection Microbiology Mice Sporozoites Vaccine antibody Rhesus P. falciparum |
author_facet |
Craig ePrzysiecki Bob eLucas Robert eMitchell Zhiyun eWen Daniel eCarapau Xin-Min eWang Debbie eNahas Chengwei eWu Robert eHepler Elizabeth eOttinger Jan eter Meulen David eKaslow John eShiver Hui eXu Elizabeth eNardin |
author_sort |
Craig ePrzysiecki |
title |
Sporozoite neutralizing antibodies elicited in mice and rhesus macaques immunized with a Plasmodium falciparum repeat peptide conjugated to meningococcal outer membrane protein complex |
title_short |
Sporozoite neutralizing antibodies elicited in mice and rhesus macaques immunized with a Plasmodium falciparum repeat peptide conjugated to meningococcal outer membrane protein complex |
title_full |
Sporozoite neutralizing antibodies elicited in mice and rhesus macaques immunized with a Plasmodium falciparum repeat peptide conjugated to meningococcal outer membrane protein complex |
title_fullStr |
Sporozoite neutralizing antibodies elicited in mice and rhesus macaques immunized with a Plasmodium falciparum repeat peptide conjugated to meningococcal outer membrane protein complex |
title_full_unstemmed |
Sporozoite neutralizing antibodies elicited in mice and rhesus macaques immunized with a Plasmodium falciparum repeat peptide conjugated to meningococcal outer membrane protein complex |
title_sort |
sporozoite neutralizing antibodies elicited in mice and rhesus macaques immunized with a plasmodium falciparum repeat peptide conjugated to meningococcal outer membrane protein complex |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Cellular and Infection Microbiology |
issn |
2235-2988 |
publishDate |
2012-11-01 |
description |
Antibodies that neutralize infectivity of malaria sporozoites target the central repeat region of the circumsporozoite (CS) protein, which in Plasmodium falciparum is comprised primarily of 30-40 tandem NANP tetramer repeats. We evaluated immunogenicity of an alum-adsorbed (NANP)6 peptide conjugated to an outer membrane protein complex (OMPC) derived from Neisseria meningitidis, a carrier protein used in a licensed H. influenzae pediatric vaccine. Mice immunized with alum-adsorbed (NANP)6-OMPC, with or without Iscomatrix© as co-adjuvant, developed high levels of anti-repeat peptide antibody that inhibited in vitro invasion of human hepatoma cells by transgenic P. berghei sporozoites that express P. falciparum CS repeats (PfPb). Inhibition of sporozoite invasion in vitro correlated with in vivo resistance to challenge by the bites of PfPb infected mosquitoes. Challenged mice had > 90% reduction of hepatic stage parasites as measured by real-time PCR, and either sterile immunity, i.e. no detectable blood stage parasites, or delayed prepatent periods which indicate neutralization of a majority, but not all, sporozoites. Rhesus macaques immunized with two doses of (NANP)6-OMPC/MAA formulated with Iscomatrix© developed anti-repeat antibodies that persisted for ~2 years. A third dose of (NANP)6-OMPC/MAA+ Iscomatrix© at that time elicited strong anamnestic antibody responses. Rhesus macaque immune sera obtained post second and third dose of vaccine displayed high levels of sporozoite neutralizing activity in vitro that correlated with presence of high anti-repeat antibody titers. These preclinical studies in mice of different MHC haplotypes and a non-human primate support use of CS peptide-OMPC conjugates as a highly immunogenic platform to evaluate CS protective epitopes. Potential pre-erythrocytic vaccines can be combined with sexual blood stage vaccines as a multi-antigen malaria vaccine to block invasion and transmission of Plasmodium parasites |
topic |
Mice Sporozoites Vaccine antibody Rhesus P. falciparum |
url |
http://journal.frontiersin.org/Journal/10.3389/fcimb.2012.00146/full |
work_keys_str_mv |
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