A Plant-produced Pfs25 VLP Malaria Vaccine Candidate Induces Persistent Transmission Blocking Antibodies Against Plasmodium Falciparum in Immunized Mice

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2013 Nov 22

PMID 24260245

Citations 60

Authors

R Mark Jones

Jessica A Chichester

Vadim Mett

Jennifer Jaje

Stephen Tottey

Slobodanka Manceva

Louis J Casta

Sandra K Gibbs

Konstantin Musiychuk

Moneim Shamloul

Joey Norikane

Valentina Mett

Stephen J Streatfield

Marga van de Vegte-Bolmer

Will Roeffen

Robert W Sauerwein

Vidadi Yusibov

Affiliations

Soon will be listed here.

Abstract

Malaria transmission blocking vaccines (TBVs) are considered an effective means to control and eventually eliminate malaria. The Pfs25 protein, expressed predominantly on the surface of the sexual and sporogonic stages of Plasmodium falciparum including gametes, zygotes and ookinetes, is one of the primary targets for TBV. It has been demonstrated that plants are an effective, highly scalable system for the production of recombinant proteins, including virus-like particles (VLPs). We engineered VLPs (Pfs25-CP VLP) comprising Pfs25 fused to the Alfalfa mosaic virus coat protein (CP) and produced these non-enveloped hybrid VLPs in Nicotiana benthamiana plants using a Tobacco mosaic virus-based 'launch' vector. Purified Pfs25-CP VLPs were highly consistent in size (19.3±2.4 nm in diameter) with an estimated 20-30% incorporation of Pfs25 onto the VLP surface. Immunization of mice with one or two doses of Pfs25-CP VLPs plus Alhydrogel® induced serum antibodies with complete transmission blocking activity through the 6 month study period. These results support the evaluation of Pfs25-CP VLP as a potential TBV candidate and the feasibility of the 'launch' vector technology for the production of VLP-based recombinant vaccines against infectious diseases.

Citing Articles

Molecular Farming for Immunization: Current Advances and Future Prospects in Plant-Produced Vaccines.

Vo D, Trinh K Vaccines (Basel). 2025; 13(2).

PMID: 40006737 PMC: 11860421. DOI: 10.3390/vaccines13020191.

Targeting Bottlenecks in Malaria Transmission: Antibody-Epitope Descriptions Guide the Design of Next-Generation Biomedical Interventions.

Yoo R, Jore M, Julien J Immunol Rev. 2025; 330(1):e70001.

PMID: 39907429 PMC: 11796336. DOI: 10.1111/imr.70001.

Virus-like Particles Produced in Plants: A Promising Platform for Recombinant Vaccine Development.

Mardanova E, Vasyagin E, Ravin N Plants (Basel). 2025; 13(24.

PMID: 39771262 PMC: 11678810. DOI: 10.3390/plants13243564.

Overview of Recombinant Tick Vaccines and Perspectives on the Use of Plant-Made Vaccines to Control Ticks of Veterinary Importance.

Trujillo E, Ramos-Vega A, Monreal-Escalante E, Almazan C, Angulo C Vaccines (Basel). 2024; 12(10).

PMID: 39460344 PMC: 11512348. DOI: 10.3390/vaccines12101178.

Recent advances in expression and purification strategies for plant made vaccines.

Venkataraman S, Khan I, Habibi P, Le M, Lippert R, Hefferon K Front Plant Sci. 2023; 14:1273958.

PMID: 38078091 PMC: 10701439. DOI: 10.3389/fpls.2023.1273958.

References

Thera M, Doumbo O, Coulibaly D, Laurens M, Kone A, Guindo A . Safety and immunogenicity of an AMA1 malaria vaccine in Malian children: results of a phase 1 randomized controlled trial. PLoS One. 2010; 5(2):e9041. PMC: 2816207. DOI: 10.1371/journal.pone.0009041. View

Agnandji S, Lell B, Fernandes J, Abossolo B, Methogo B, Lumeka Kabwende A . A phase 3 trial of RTS,S/AS01 malaria vaccine in African infants. N Engl J Med. 2012; 367(24):2284-95. PMC: 10915853. DOI: 10.1056/NEJMoa1208394. View

McLain L, Porta C, Lomonossoff G, Durrani Z, Dimmock N . Human immunodeficiency virus type 1-neutralizing antibodies raised to a glycoprotein 41 peptide expressed on the surface of a plant virus. AIDS Res Hum Retroviruses. 1995; 11(3):327-34. DOI: 10.1089/aid.1995.11.327. View

Brewer J, Conacher M, Hunter C, Mohrs M, Brombacher F, Alexander J . Aluminium hydroxide adjuvant initiates strong antigen-specific Th2 responses in the absence of IL-4- or IL-13-mediated signaling. J Immunol. 1999; 163(12):6448-54. View

Kubler-Kielb J, Majadly F, Wu Y, Narum D, Guo C, Miller L . Long-lasting and transmission-blocking activity of antibodies to Plasmodium falciparum elicited in mice by protein conjugates of Pfs25. Proc Natl Acad Sci U S A. 2006; 104(1):293-8. PMC: 1765452. DOI: 10.1073/pnas.0609885104. View

Wu Y, Ellis R, Shaffer D, Fontes E, Malkin E, Mahanty S . Phase 1 trial of malaria transmission blocking vaccine candidates Pfs25 and Pvs25 formulated with montanide ISA 51. PLoS One. 2008; 3(7):e2636. PMC: 2440546. DOI: 10.1371/journal.pone.0002636. View

Cech P, Aebi T, Abdallah M, Mpina M, Machunda E, Westerfeld N . Virosome-formulated Plasmodium falciparum AMA-1 & CSP derived peptides as malaria vaccine: randomized phase 1b trial in semi-immune adults & children. PLoS One. 2011; 6(7):e22273. PMC: 3142124. DOI: 10.1371/journal.pone.0022273. View

Yusibov V, Streatfield S, Kushnir N, Roy G, Padmanaban A . Hybrid viral vectors for vaccine and antibody production in plants. Curr Pharm Des. 2013; 19(31):5574-86. DOI: 10.2174/13816128113199990335. View

Tsai C, Duggan P, Shimp Jr R, Miller L, Narum D . Overproduction of Pichia pastoris or Plasmodium falciparum protein disulfide isomerase affects expression, folding and O-linked glycosylation of a malaria vaccine candidate expressed in P. pastoris. J Biotechnol. 2005; 121(4):458-70. DOI: 10.1016/j.jbiotec.2005.08.025. View

10.

Yusibov V, Hooper D, Spitsin S, Fleysh N, Kean R, Mikheeva T . Expression in plants and immunogenicity of plant virus-based experimental rabies vaccine. Vaccine. 2002; 20(25-26):3155-64. DOI: 10.1016/s0264-410x(02)00260-8. View

11.

Qian F, Rausch K, Muratova O, Zhou H, Song G, Diouf A . Addition of CpG ODN to recombinant Pseudomonas aeruginosa ExoProtein A conjugates of AMA1 and Pfs25 greatly increases the number of responders. Vaccine. 2008; 26(20):2521-7. PMC: 2426823. DOI: 10.1016/j.vaccine.2008.03.005. View

12.

Oyewumi M, Kumar A, Cui Z . Nano-microparticles as immune adjuvants: correlating particle sizes and the resultant immune responses. Expert Rev Vaccines. 2010; 9(9):1095-107. PMC: 2963573. DOI: 10.1586/erv.10.89. View

13.

Hill A . Vaccines against malaria. Philos Trans R Soc Lond B Biol Sci. 2011; 366(1579):2806-14. PMC: 3146776. DOI: 10.1098/rstb.2011.0091. View

14.

Durrani Z, McInerney T, McLain L, Jones T, Bellaby T, Brennan F . Intranasal immunization with a plant virus expressing a peptide from HIV-1 gp41 stimulates better mucosal and systemic HIV-1-specific IgA and IgG than oral immunization. J Immunol Methods. 1998; 220(1-2):93-103. DOI: 10.1016/s0022-1759(98)00145-8. View

15.

Mett V, Farrance C, Green B, Yusibov V . Plants as biofactories. Biologicals. 2008; 36(6):354-8. DOI: 10.1016/j.biologicals.2008.09.001. View

16.

Kushnir N, Streatfield S, Yusibov V . Virus-like particles as a highly efficient vaccine platform: diversity of targets and production systems and advances in clinical development. Vaccine. 2012; 31(1):58-83. PMC: 7115575. DOI: 10.1016/j.vaccine.2012.10.083. View

17.

Yusibov V, Streatfield S, Kushnir N . Clinical development of plant-produced recombinant pharmaceuticals: vaccines, antibodies and beyond. Hum Vaccin. 2011; 7(3):313-21. DOI: 10.4161/hv.7.3.14207. View

18.

Chichester J, Musiychuk K, Farrance C, Mett V, Lyons J, Mett V . A single component two-valent LcrV-F1 vaccine protects non-human primates against pneumonic plague. Vaccine. 2009; 27(25-26):3471-4. DOI: 10.1016/j.vaccine.2009.01.050. View

19.

Outchkourov N, Vermunt A, Jansen J, Kaan A, Roeffen W, Teelen K . Epitope analysis of the malaria surface antigen pfs48/45 identifies a subdomain that elicits transmission blocking antibodies. J Biol Chem. 2007; 282(23):17148-56. DOI: 10.1074/jbc.M700948200. View

20.

Musiychuk K, Stephenson N, Bi H, Farrance C, Orozovic G, Brodelius M . A launch vector for the production of vaccine antigens in plants. Influenza Other Respir Viruses. 2009; 1(1):19-25. PMC: 4634661. DOI: 10.1111/j.1750-2659.2006.00005.x. View