Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Malaria Journal
Published in: Malaria Journal 1/2007

Open Access 01-12-2007 | Research

Transmission-blocking activity induced by malaria vaccine candidates Pfs25/Pvs25 is a direct and predictable function of antibody titer

Authors: Kazutoyo Miura, David B Keister, Olga V Muratova, Jetsumon Sattabongkot, Carole A Long, Allan Saul

Published in: Malaria Journal | Issue 1/2007

Login to get access

Abstract

Background

Mosquito stage malaria vaccines are designed to induce an immune response in the human host that will block the parasite's growth in the mosquito and consequently block transmission of the parasite. A mosquito membrane-feeding assay (MFA) is used to test transmission-blocking activity (TBA), but in this technique cannot accommodate many samples. A clear understanding of the relationship between antibody levels and TBA may allow ELISA determinations to be used to predict TBA and assist in planning vaccine development.

Methods

Rabbit anti-Pfs25 sera and monkey anti-Pvs25 sera were generated and the antibody titers were determined by a standardized ELISA. The biological activity of the same sera was tested by MFA using Plasmodium gametocytes (cultured Plasmodium falciparum or Plasmodium vivax from malaria patients) and Anopheles mosquitoes.

Results

Anti-Pfs25 and anti-Pvs25 sera showed that ELISA antibody units correlate with the percent reduction in the oocyst density per mosquito (Spearman Rank correlations: 0.934 and 0.616, respectively), and fit a hyperbolic curve when percent reduction in oocyst density is plotted against antibody units of the tested sample. Antibody levels also correlated with the number of mosquitoes that failed to become infected, and this proportion can be calculated from the reduction in oocyst numbers and the distribution of oocysts per infected mosquito in control group.

Conclusion

ELISA data may be used as a surrogate for the MFA to evaluate transmission-blocking vaccine efficacy. This will facilitate the evaluation of transmission-blocking vaccines and implementation of this malaria control strategy.
Appendix
Available only for authorised users
Literature
1.
2.
Ballou WR, Arevalo-Herrera M, Carucci D, Richie TL, Corradin G, Diggs C, Druilhe P, Giersing BK, Saul A, Heppner DG, Kester KE, Lanar DE, Lyon J, Hill AV, Pan W, Cohen JD: Update on the clinical development of candidate malaria vaccines. Am J Trop Med Hyg. 2004, 71: 239-247.PubMed
3.
Carter R, Mendis KN, Miller LH, Molineaux L, Saul A: Malaria transmission-blocking vaccines--how can their development be supported?. Nat Med. 2000, 6: 241-244. 10.1038/73062.CrossRefPubMed
4.
Smith TA, Leuenberger R, Lengeler C: Child mortality and malaria transmission intensity in Africa. Trends Parasitol. 2001, 17: 145-149. 10.1016/S1471-4922(00)01814-6.CrossRefPubMed
5.
Alonso PL, Sacarlal J, Aponte JJ, Leach A, Macete E, Aide P, Sigauque B, Milman J, Mandomando I, Bassat Q, Guinovart C, Espasa M, Corachan S, Lievens M, Navia MM, Dubois MC, Menendez C, Dubovsky F, Cohen J, Thompson R, Ballou WR: Duration of protection with RTS,S/AS02A malaria vaccine in prevention of Plasmodium falciparum disease in Mozambican children: single-blind extended follow-up of a randomised controlled trial. Lancet. 2005, 366: 2012-2018. 10.1016/S0140-6736(05)67669-6.CrossRefPubMed
6.
Alonso PL, Lindsay SW, Armstrong JR, Conteh M, Hill AG, David PH, Fegan G, De-Francisco A, Hall AJ, Shenton FC, Greenwood BM, Conteh M, Cham K, Hill AG, David PH, Fegan G, Hall AJ: The effect of insecticide-treated bed nets on mortality of Gambian children. Lancet. 1991, 337: 1499-1502. 10.1016/0140-6736(91)93194-E.CrossRefPubMed
7.
Binka FN, Kubaje A, Adjuik M, Williams LA, Lengeler C, Maude GH, Armah GE, Kajihara B, Adiamah JH, Smith PG: Impact of permethrin impregnated bednets on child mortality in Kassena-Nankana district, Ghana: a randomized controlled trial. Trop Med Int Health. 1996, 1: 147-154.CrossRefPubMed
8.
Nevill CG, Some ES, Mung'ala VO, Mutemi W, New L, Marsh K, Lengeler C, Snow RW: Insecticide-treated bednets reduce mortality and severe morbidity from malaria among children on the Kenyan coast. Trop Med Int Health. 1996, 1: 139-146.CrossRefPubMed
9.
Saxena AK, Singh K, Su HP, Klein MM, Stowers AW, Saul AJ, Long CA, Garboczi DN: The essential mosquito-stage P25 and P28 proteins from Plasmodium form tile-like triangular prisms. Nat Struct Mol Biol. 2005
10.
Kaslow DC, Quakyi IA, Syin C, Raum MG, Keister DB, Coligan JE, McCutchan TF, Miller LH: A vaccine candidate from the sexual stage of human malaria that contains EGF-like domains. Nature. 1988, 333: 74-76. 10.1038/333074a0.CrossRefPubMed
11.
Tsuboi T, Kaslow DC, Gozar MMG, Tachibana M, Cao YM, Torii M: Sequence polymorphism in two novel Plasmodium vivax ookinete surface proteins, Pvs25 and Pvs28, that are malaria transmission-blocking vaccine candidates. Mol Med. 1998, 4: 772-782.PubMedCentralPubMed
12.
Kaslow DC, Quakyi IA, Keister DB: Minimal variation in a vaccine candidate from the sexual stage of Plasmodium falciparum. Mol Biochem Parasitol. 1989, 32: 101-103. 10.1016/0166-6851(89)90134-5.CrossRefPubMed
13.
Shi YP, Alpers MP, Povoa MM, Lal AA: Single amino acid variation in the ookinete vaccine antigen from field isolates of Plasmodium falciparum. Mol Biochem Parasitol. 1992, 50: 179-180. 10.1016/0166-6851(92)90254-H.CrossRefPubMed
14.
Barr PJ, Green KM, Gibson HL, Bathurst IC, Quakyi IA, Kaslow DC: Recombinant Pfs25 protein of Plasmodium falciparum elicits malaria transmission-blocking immunity in experimental animals. J Exp Med. 1991, 174: 1203-1208. 10.1084/jem.174.5.1203.CrossRefPubMed
15.
Hisaeda H, Stowers AW, Tsuboi T, Collins WE, Sattabongkot JS, Suwanabun N, Torii M, Kaslow DC: Antibodies to malaria vaccine candidates Pvs25 and Pvs28 completely block the ability of Plasmodium vivax to infect mosquitoes. Infect Immun. 2000, 68: 6618-6623. 10.1128/IAI.68.12.6618-6623.2000.PubMedCentralCrossRefPubMed
16.
Kaslow DC, Shiloach J: Production, purification and immunogenicity of a malaria transmission-blocking vaccine candidate: TBV25H expressed in yeast and purified using nickel-NTA agarose. Biotechnology N Y. 1994, 12: 494-499. 10.1038/nbt0594-494.CrossRefPubMed
17.
Stowers AW, Keister DB, Muratova O, Kaslow DC: A region of Plasmodium falciparum antigen pfs25 that is the target of highly potent transmission-blocking antibodies. Infect Immun. 2000, 68: 5530-5538. 10.1128/IAI.68.10.5530-5538.2000.PubMedCentralCrossRefPubMed
18.
Gozar MMG, Muratova O, Keister DB, Kensil CR, Price VL, Kaslow DC: Plasmodium falciparum: immunogenicity of alum-adsorbed clinical-grade TBV25-28, a yeast-secreted malaria transmission-blocking vaccine candidate. Exp Parasitol. 2001, 97: 61-69. 10.1006/expr.2000.4580.CrossRefPubMed
19.
Kaslow DC, Bathurst IC, Lensen T, Ponnudurai T, Barr PJ, Keister DB: Saccharomyces cerevisiae recombinant Pfs25 adsorbed to alum elicits antibodies that block transmission of Plasmodium falciparum. Infect Immun. 1994, 62: 5576-5580.PubMedCentralPubMed
20.
Collins WE, Barnwell JW, Sullivan JS, Nace D, Williams T, Bounngaseng A, Roberts J, Strobert E, McClure H, Saul A, Long CA: Assessment of transmission-blocking activity of candidate Pvs25 vaccine using gametocytes from chimpanzees. Am J Trop Med Hyg. 2006, 74: 215-221.PubMed
21.
Malkin EM, Durbin AP, Diemert DJ, Sattabongkot J, Wu Y, Miura K, Long CA, Lambert L, Miles AP, Wang J, Stowers A, Miller LH, Saul A: Phase 1 vaccine trial of Pvs25H: a transmission blocking vaccine for Plasmodium vivax malaria. Vaccine. 2005, 23: 3131-3138. 10.1016/j.vaccine.2004.12.019.CrossRefPubMed
22.
Bousema JT, Drakeley CJ, Kihonda J, Hendriks JC, Akim NI, Roeffen W, Sauerwein RW: A longitudinal study of immune responses to Plasmodium falciparum sexual stage antigens in Tanzanian adults. Parasite Immunol. 2007, 29: 309-317. 10.1111/j.1365-3024.2007.00948.x.CrossRefPubMed
23.
Drakeley CJ, Eling W, Teelen K, Bousema JT, Sauerwein R, Greenwood BM, Targett GA: Parasite infectivity and immunity to Plasmodium falciparum gametocytes in Gambian children. Parasite Immunol. 2004, 26: 159-165. 10.1111/j.0141-9838.2004.00696.x.CrossRefPubMed
24.
Outchkourov N, Vermunt A, Jansen J, Kaan A, Roeffen W, Teelen K, Lasonder E, Braks A, van , Qiu LY, Sauerwein R, Stunnenberg HG: Epitope analysis of the malaria surface antigen pfs48/45 identifies a subdomain that elicits transmission blocking antibodies. J Biol Chem. 2007, 282: 17148-17156. 10.1074/jbc.M700948200.CrossRefPubMed
25.
Zou L, Miles AP, Wang J, Stowers AW: Expression of malaria transmission-blocking vaccine antigen Pfs25 in Pichia pastoris for use in human clinical trials. Vaccine. 2003, 21: 1650-1657. 10.1016/S0264-410X(02)00701-6.CrossRefPubMed
26.
Miles AP, Zhang Y, Saul A, Stowers AW: Large-Scale Purification and Characterization of Malaria Vaccine Candidate Antigen Pvs25H for Use in Clinical Trials. Protein Expr Purif. 2002, 25: 87-96. 10.1006/prep.2001.1613.CrossRefPubMed
27.
Kashala O, Amador R, Valero MV, Moreno A, Barbosa A, Nickel B, Daubenberger CA, Guzman F, Pluschke G, Patarroyo ME: Safety, tolerability and immunogenicity of new formulations of the Plasmodium falciparum malaria peptide vaccine SPf66 combined with the immunological adjuvant QS-21. Vaccine. 2002, 20: 2263-2277. 10.1016/S0264-410X(02)00115-9.CrossRefPubMed
28.
Nardin EH, Oliveira GA, Calvo-Calle JM, Castro ZR, Nussenzweig RS, Schmeckpeper B, Hall BF, Diggs C, Bodison S, Edelman R: Synthetic Malaria Peptide Vaccine Elicits High Levels of Antibodies in Vaccinees of Defined HLA Genotypes. J Infect Dis. 2000, 182: 1486-1496. 10.1086/315871.CrossRefPubMed
29.
Xiao L, Rafi-Janajreh A, Patterson P, Zhou Z, Lal AA: Adjuvants and malaria vaccine development. Chem Immunol. 2002, 80: 343-365.CrossRefPubMed
30.
Collins WE, Walduck A, Sullivan JS, Andrews K, Stowers A, Morris CL, Jennings V, Yang C, Kendall J, Lin Q, Martin LB, Diggs C, Saul A: Efficacy of vaccines containing rhoptry-associated proteins RAP1 and RAP2 of Plasmodium falciparum in Saimiri boliviensis monkeys. Am J Trop Med Hyg. 2000, 62: 466-479.PubMed
31.
Dutta S, Ware LA, Barbosa A, Ockenhouse CF, Lanar DE: Purification, characterization, and immunogenicity of a disulfide cross-linked Plasmodium vivax vaccine candidate antigen, merozoite surface protein 1, expressed in Escherichia coli. Infect Immun. 2001, 69: 5464-5470. 10.1128/IAI.69.9.5464-5470.2001.PubMedCentralCrossRefPubMed
32.
Hirunpetcharat C, Wipasa J, Sakkhachornphop S, Nitkumhan T, Zheng YZ, Pichyangkul S, Krieg AM, Walsh DS, Heppner DG, Good MF: CpG oligodeoxynucleotide enhances immunity against blood-stage malaria infection in mice parenterally immunized with a yeast-expressed 19 kDa carboxyl-terminal fragment of Plasmodium yoelii merozoite surface protein-1 (MSP1(19)) formulated in oil-based Montanides. Vaccine. 2003, 21: 2923-2932. 10.1016/S0264-410X(03)00132-4.CrossRefPubMed
33.
Hodder AN, Crewther PE, Anders RF: Specificity of the protective antibody response to apical membrane antigen 1. Infect Immun. 2001, 69: 3286-3294. 10.1128/IAI.69.5.3286-3294.2001.PubMedCentralCrossRefPubMed
34.
Jones GL, Spencer L, Lord R, Mollard R, Pye D, Saul A: Peptide vaccines derived from a malarial surface antigen: effects of dose and adjuvants on immunogenicity. Immunol Lett. 1990, 24: 253-260. 10.1016/0165-2478(90)90008-E.CrossRefPubMed
35.
Genton B, Al-Yaman F, Anders R, Saul A, Brown G, Pye D, Irving DO, Briggs WR, Mai A, Ginny M, Adiguma T, Rare L, Giddy A, Reber-Liske R, Stuerchler D, Alpers MP: Safety and immunogenicity of a three-component blood-stage malaria vaccine in adults living in an endemic area of Papua New Guinea. Vaccine. 2000, 18: 2504-2511. 10.1016/S0264-410X(00)00036-0.CrossRefPubMed
36.
Lawrence GW, Saul A, Giddy AJ, Kemp R, Pye D: Phase I trial in humans of an oil-based adjuvant SEPPIC MONTANIDE ISA 720. Vaccine. 1997, 15: 176-178. 10.1016/S0264-410X(96)00150-8.CrossRefPubMed
37.
Saul A, Lawrence G, Smillie A, Rzepczyk CM, Reed C, Taylor D, Anderson K, Stowers A, Kemp R, Allworth A, Anders RF, Brown GV, Pye D, Schoofs P, Irving DO, Dyer SL, Woodrow GC, Briggs WRS, Reber R, Stürcher D: Human phase I vaccine trials of 3 recombinant asexual stage malaria antigens with Montanide ISA720 adjuvant. Vaccine. 1999, 17: 3145-3159. 10.1016/S0264-410X(99)00175-9.CrossRefPubMed
38.
Yamamoto S, Yamamoto T, Kataoka T, Kuramoto E, Yano O, Tokunaga T: Unique palindromic sequences in synthetic oligonucleotides are required to induce IFN and augment IFN-mediated natural killer activity. J Immunol. 1992, 148: 4072-4076.PubMed
39.
Krieg AM, Yi AK, Matson S, Waldschmidt TJ, Bishop GA, Teasdale R, Koretzky GA, Klinman DM: CpG motifs in bacterial DNA trigger direct B-cell activation. Nature. 1995, 374: 546-549. 10.1038/374546a0.CrossRefPubMed
40.
Chu RS, Targoni OS, Krieg AM, Lehmann PV, Harding CV: CpG oligodeoxynucleotides act as adjuvants that switch on T helper 1 (Th1) immunity. J Exp Med. 1997, 186: 1623-1631. 10.1084/jem.186.10.1623.PubMedCentralCrossRefPubMed
41.
Davis HL, Weeratna R, Waldschmidt TJ, Tygrett L, Schorr J, Krieg AM: CpG DNA is a potent enhancer of specific immunity in mice immunized with recombinant hepatitis B surface antigen. J Immunol. 1998, 160: 870-876.PubMed
42.
Weiner GJ, Liu HM, Wooldridge JE, Dahle CE, Krieg AM: Immunostimulatory oligodeoxynucleotides containing the CpG motif are effective as immune adjuvants in tumor antigen immunization. Proc Natl Acad Sci U S A. 1997, 94: 10833-10837. 10.1073/pnas.94.20.10833.PubMedCentralCrossRefPubMed
43.
Sato Y, Roman M, Tighe H, Lee D, Corr M, Nguyen MD, Silverman GJ, Lotz M, Carson DA, Raz E: Immunostimulatory DNA sequences necessary for effective intradermal gene immunization. Science. 1996, 273: 352-354. 10.1126/science.273.5273.352.CrossRefPubMed
44.
Halperin SA, Van Nest G, Smith B, Abtahi S, Whiley H, Eiden JJ: A phase I study of the safety and immunogenicity of recombinant hepatitis B surface antigen co-administered with an immunostimulatory phosphorothioate oligonucleotide adjuvant. Vaccine. 2003, 21: 2461-2467. 10.1016/S0264-410X(03)00045-8.CrossRefPubMed
45.
Krieg AM: CpG motifs: the active ingredient in bacterial extracts?. Nat Med. 2003, 9: 831-835. 10.1038/nm0703-831.CrossRefPubMed
46.
Roman M, Martin-Orozco E, Goodman JS, Nguyen MD, Sato Y, Ronaghy A, Kornbluth RS, Richman DD, Carson DA, Raz E: Immunostimulatory DNA sequences function as T helper-1-promoting adjuvants. Nat Med. 1997, 3: 849-854. 10.1038/nm0897-849.CrossRefPubMed
47.
Stowers AW, Keister DB, Muratova O, Kaslow DC: A region of plasmodium falciparum antigen pfs25 that is the target of highly potent transmission-blocking antibodies. Infect Immun. 2000, 68: 5530-5538. 10.1128/IAI.68.10.5530-5538.2000.PubMedCentralCrossRefPubMed
48.
Toure YT, Doumbo O, Toure A, Bagayoko M, Diallo M, Dolo A, Vernick KD, Keister DB, Muratova O, Kaslow DC: Gametocyte infectivity by direct mosquito feeds in an area of seasonal malaria transmission: implications for Bancoumana, Mali as a transmission-blocking vaccine site. Am J Trop Med Hyg. 1998, 59: 481-486.PubMed
49.
Medley GF, Sinden RE, Fleck S, Billingsley PF, Tirawanchai N, Rodriguez MH: Heterogeneity in patterns of malarial oocyst infections in the mosquito vector. Parasitology. 1993, 106: 441-449.CrossRefPubMed
50.
M. K, de Vlas SJ, Saul A, van , Eling WM, Sauerwein RW: Evaluation of the standard membrane feeding assay (SMFA) for the determination of malaria transmission-reducing activity using empirical data. Parasitology. 2005, 130: 13-22. 10.1017/S0031182004006067.CrossRef
Metadata
Title
Transmission-blocking activity induced by malaria vaccine candidates Pfs25/Pvs25 is a direct and predictable function of antibody titer
Authors
Kazutoyo Miura
David B Keister
Olga V Muratova
Jetsumon Sattabongkot
Carole A Long
Allan Saul
Publication date
01-12-2007
Publisher
BioMed Central
Published in
Malaria Journal / Issue 1/2007
Electronic ISSN: 1475-2875
DOI
https://doi.org/10.1186/1475-2875-6-107

Other articles of this Issue 1/2007

Malaria Journal 1/2007 Go to the issue

Case report

Severe sepsis due to severe falciparum malaria and leptospirosis co-infection treated with activated protein C

Review

World Antimalarial Resistance Network I: Clinical efficacy of antimalarial drugs

Research

Treatment-seeking behaviour for febrile illness in an area of seasonal malaria transmission in rural Ethiopia

Research

Malaria vector control by indoor residual insecticide spraying on the tropical island of Bioko, Equatorial Guinea

Research

Evaluation of the intra- and inter-specific genetic variability of Plasmodium lactate dehydrogenase

Case study

Outcome of life-threatening malaria in African children requiring endotracheal intubation
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits