Protection Induced by Plasmodium Falciparum MSP1(42) is Strain-specific, Antigen and Adjuvant Dependent, and Correlates with Antibody Responses

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2008 Jul 31

PMID 18665258

Citations 48

Authors

Jeffrey A Lyon

Evelina Angov

Michael P Fay

JoAnn S Sullivan

Autumn S Girourd

Sally J Robinson

Elke S Bergmann-Leitner

Elizabeth H Duncan

Christian A Darko

William E Collins

Carole A Long

John W Barnwell

Affiliations

Soon will be listed here.

Abstract

Vaccination with Plasmodium falciparum MSP1(42)/complete Freund's adjuvant (FA) followed by MSP1(42)/incomplete FA is the only known regimen that protects Aotus nancymaae monkeys against infection by erythrocytic stage malaria parasites. The role of adjuvant is not defined; however complete FA cannot be used in humans. In rodent models, immunity is strain-specific. We vaccinated Aotus monkeys with the FVO or 3D7 alleles of MSP1(42) expressed in Escherichia coli or with the FVO allele expressed in baculovirus (bv) combined with complete and incomplete FA, Montanide ISA-720 (ISA-720) or AS02A. Challenge with FVO strain P. falciparum showed that suppression of cumulative day 11 parasitemia was strain-specific and could be induced by E. coli expressed MSP1(42) in combination with FA or ISA-720 but not with AS02A. The coli42-FVO antigen induced a stronger protective effect than the bv42-FVO antigen, and FA induced a stronger protective effect than ISA-720. ELISA antibody (Ab) responses at day of challenge (DOC) were strain-specific and correlated inversely with c-day 11 parasitemia (r = -0.843). ELISA Ab levels at DOC meeting a titer of at least 115,000 ELISA Ab units identified the vaccinees not requiring treatment (noTx) with a true positive rate of 83.3% and false positive rate of 14.3 %. Correlation between functional growth inhibitory Ab levels (GIA) and cumulative day 11 parasitemia was weaker (r = -0.511), and was not as predictive for a response of noTx. The lowest false positive rate for GIA was 30% when requiring a true positive rate of 83.3%. These inhibition results along with those showing that antigen/FA combinations induced a stronger protective immunity than antigen/ISA-720 or antigen/AS02 combinations are consistent with protection as ascribed to MSP1-specific cytophilic antibodies. Development of an effective MSP1(42) vaccine against erythrocytic stage P. falciparum infection will depend not only on antigen quality, but also upon the selection of an optimal adjuvant component.

Citing Articles

Diversity and selection analyses identify transmission-blocking antigens as the optimal vaccine candidates in Plasmodium falciparum.

Ciubotariu I, Broyles B, Xie S, Thimmapuram J, Mwenda M, Mambwe B EBioMedicine. 2024; 106:105227.

PMID: 39018754 PMC: 11663769. DOI: 10.1016/j.ebiom.2024.105227.

Natural Infection Stimulates Human Antibodies to MSP1 Epitopes Identified in Mice Infection Models upon Non-Natural Modified Peptidomimetic Vaccination.

Rodriguez Z, Melo F, Torres A, Agrawal N, Cortes-Vecino J, Lozano J Molecules. 2023; 28(6).

PMID: 36985500 PMC: 10057838. DOI: 10.3390/molecules28062527.

Orientation of Antigen Display on Self-Assembling Protein Nanoparticles Influences Immunogenicity.

Schneider C, Taylor J, Sibilo M, Miura K, Mallory K, Mann C Vaccines (Basel). 2021; 9(2).

PMID: 33572803 PMC: 7911071. DOI: 10.3390/vaccines9020103.

The Search of a Malaria Vaccine: The Time for Modified Immuno-Potentiating Probes.

Lozano J, Rodriguez Parra Z, Hernandez-Martinez S, Fernanda Yasnot-Acosta M, Rojas A, Marin-Waldo L Vaccines (Basel). 2021; 9(2).

PMID: 33540947 PMC: 7913233. DOI: 10.3390/vaccines9020115.

Plasmodium vivax Pv12 B-cell epitopes and HLA-DRβ1*-dependent T-cell epitopes in vitro antigenicity.

Yepes-Perez Y, Lopez C, Suarez C, Patarroyo M PLoS One. 2018; 13(9):e0203715.

PMID: 30199554 PMC: 6130872. DOI: 10.1371/journal.pone.0203715.

References

Chang S, Case S, Gosnell W, Hashimoto A, Kramer K, Tam L . A recombinant baculovirus 42-kilodalton C-terminal fragment of Plasmodium falciparum merozoite surface protein 1 protects Aotus monkeys against malaria. Infect Immun. 1996; 64(1):253-61. PMC: 173753. DOI: 10.1128/iai.64.1.253-261.1996. View

Angov E, Hillier C, Kincaid R, Lyon J . Heterologous protein expression is enhanced by harmonizing the codon usage frequencies of the target gene with those of the expression host. PLoS One. 2008; 3(5):e2189. PMC: 2364656. DOI: 10.1371/journal.pone.0002189. View

Darko C, Angov E, Collins W, Bergmann-Leitner E, Girouard A, Hitt S . The clinical-grade 42-kilodalton fragment of merozoite surface protein 1 of Plasmodium falciparum strain FVO expressed in Escherichia coli protects Aotus nancymai against challenge with homologous erythrocytic-stage parasites. Infect Immun. 2004; 73(1):287-97. PMC: 538964. DOI: 10.1128/IAI.73.1.287-297.2005. View

Blackman M, Holder A . Secondary processing of the Plasmodium falciparum merozoite surface protein-1 (MSP1) by a calcium-dependent membrane-bound serine protease: shedding of MSP133 as a noncovalently associated complex with other fragments of the MSP1. Mol Biochem Parasitol. 1992; 50(2):307-15. DOI: 10.1016/0166-6851(92)90228-c. View

Stoute J, Slaoui M, Heppner D, Momin P, Kester K, Desmons P . A preliminary evaluation of a recombinant circumsporozoite protein vaccine against Plasmodium falciparum malaria. RTS,S Malaria Vaccine Evaluation Group. N Engl J Med. 1997; 336(2):86-91. DOI: 10.1056/NEJM199701093360202. View

Miura K, Zhou H, Muratova O, Orcutt A, Giersing B, Miller L . In immunization with Plasmodium falciparum apical membrane antigen 1, the specificity of antibodies depends on the species immunized. Infect Immun. 2007; 75(12):5827-36. PMC: 2168362. DOI: 10.1128/IAI.00593-07. View

Kumar S, Yadava A, Keister D, Tian J, Ohl M, MILLER L . Immunogenicity and in vivo efficacy of recombinant Plasmodium falciparum merozoite surface protein-1 in Aotus monkeys. Mol Med. 1995; 1(3):325-32. PMC: 2229908. View

Sing T, Sander O, Beerenwinkel N, Lengauer T . ROCR: visualizing classifier performance in R. Bioinformatics. 2005; 21(20):3940-1. DOI: 10.1093/bioinformatics/bti623. View

CHAPPEL J, Holder A . Monoclonal antibodies that inhibit Plasmodium falciparum invasion in vitro recognise the first growth factor-like domain of merozoite surface protein-1. Mol Biochem Parasitol. 1993; 60(2):303-11. DOI: 10.1016/0166-6851(93)90141-j. View

10.

Blackman M, HEIDRICH H, Donachie S, McBride J, Holder A . A single fragment of a malaria merozoite surface protein remains on the parasite during red cell invasion and is the target of invasion-inhibiting antibodies. J Exp Med. 1990; 172(1):379-82. PMC: 2188181. DOI: 10.1084/jem.172.1.379. View

11.

Cohen S, McGregor I, Carrington S . Gamma-globulin and acquired immunity to human malaria. Nature. 1961; 192:733-7. DOI: 10.1038/192733a0. View

12.

Sachdeva S, Mohmmed A, Dasaradhi P, Crabb B, Katyal A, Malhotra P . Immunogenicity and protective efficacy of Escherichia coli expressed Plasmodium falciparum merozoite surface protein-1(42) using human compatible adjuvants. Vaccine. 2005; 24(12):2007-16. DOI: 10.1016/j.vaccine.2005.11.041. View

13.

Holder A . Proteins on the surface of the malaria parasite and cell invasion. Parasitology. 1994; 108 Suppl:S5-18. DOI: 10.1017/s0031182000075673. View

14.

Jin B, Wang R, Qiu Q, Sugauchi F, Grandinetti T, Alter H . Induction of potent cellular immune response in mice by hepatitis C virus NS3 protein with double-stranded RNA. Immunology. 2007; 122(1):15-27. PMC: 2265985. DOI: 10.1111/j.1365-2567.2007.02607.x. View

15.

Segal B, Chang J, Shevach E . CpG oligonucleotides are potent adjuvants for the activation of autoreactive encephalitogenic T cells in vivo. J Immunol. 2000; 164(11):5683-8. DOI: 10.4049/jimmunol.164.11.5683. View

16.

Singh S, Miura K, Zhou H, Muratova O, Keegan B, Miles A . Immunity to recombinant plasmodium falciparum merozoite surface protein 1 (MSP1): protection in Aotus nancymai monkeys strongly correlates with anti-MSP1 antibody titer and in vitro parasite-inhibitory activity. Infect Immun. 2006; 74(8):4573-80. PMC: 1539572. DOI: 10.1128/IAI.01679-05. View

17.

Miller L, Saul A, Mahanty S . Revisiting Freund's incomplete adjuvant for vaccines in the developing world. Trends Parasitol. 2005; 21(9):412-4. DOI: 10.1016/j.pt.2005.07.005. View

18.

Bergmann-Leitner E, Duncan E, Burge J, Spring M, Angov E . Miniaturization of a high-throughput pLDH-based Plasmodium falciparum growth inhibition assay for small volume samples from preclinical and clinical vaccine trials. Am J Trop Med Hyg. 2008; 78(3):468-71. View

19.

Siddiqui W, Tam L, Kramer K, Hui G, Case S, Yamaga K . Merozoite surface coat precursor protein completely protects Aotus monkeys against Plasmodium falciparum malaria. Proc Natl Acad Sci U S A. 1987; 84(9):3014-8. PMC: 304791. DOI: 10.1073/pnas.84.9.3014. View

20.

Goel V, Li X, Chen H, Liu S, Chishti A, Oh S . Band 3 is a host receptor binding merozoite surface protein 1 during the Plasmodium falciparum invasion of erythrocytes. Proc Natl Acad Sci U S A. 2003; 100(9):5164-9. PMC: 154316. DOI: 10.1073/pnas.0834959100. View