Malaria vaccine candidates displayed on novel virus-like particles are immunogenic and induce transmission-blocking activity

ABSTRACTThe development of effective malaria vaccines remains a global health priority. Currently, the most advanced vaccine, known as RTS,S, has only shown modest efficacy in clinical trials. Thus, the development of more efficacious vaccines by improving the formulation of RTS,S for increased efficacy or to interrupt malaria transmission are urgently needed. The RTS,S vaccine is based on the presentation of a fragment of the sporozoite antigen on the surface of virus-like particles (VLPs) based on human hepatitis B virus (HBV). In this study, we have developed and evaluated a novel VLP platform based on duck HBV (known as Metavax) for malaria vaccine development. This platform can incorporate large and complex proteins into VLPs and is produced in a Hansenula cell line compatible with cGMP vaccine production. Here, we have established the expression of leading P. falciparum malaria vaccine candidates as VLPs. This includes Pfs230 and Pfs25, which are candidate transmission-blocking vaccine antigens. We demonstrated that the VLPs effectively induce antibodies to malaria vaccine candidates with minimal induction of antibodies to the duck-HBV scaffold antigen. Antibodies to Pfs230 also recognised native protein on the surface of gametocytes, and antibodies to both Pfs230 and Pfs25 demonstrated transmission-reducing activity in standard membrane feeding assays. These results establish the potential utility of this VLP platform for malaria vaccines, which may be suitable for the development of multi-component vaccines that achieve high vaccine efficacy and transmission-blocking immunity.

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

Malaria Journal ◽

10.1186/1475-2875-6-107 ◽

2007 ◽

Vol 6 (1) ◽

Cited By ~ 60

Author(s):

Kazutoyo Miura ◽

David B Keister ◽

Olga V Muratova ◽

Jetsumon Sattabongkot ◽

Carole A Long ◽

...

Keyword(s):

Antibody Titer ◽

Malaria Vaccine ◽

Transmission Blocking ◽

Vaccine Candidates ◽

Blocking Activity

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Cloning, expression and transmission-blocking activity of anti-PvWARP, malaria vaccine candidate, in Anopheles stephensi mysorensis

Malaria Journal ◽

10.1186/1475-2875-9-158 ◽

2010 ◽

Vol 9 (1) ◽

pp. 158 ◽

Cited By ~ 4

Author(s):

Saber Gholizadeh ◽

Hamid Basseri ◽

Sedigheh Zakeri ◽

Hossein Ladoni ◽

Navid Djadid

Keyword(s):

Malaria Vaccine ◽

Anopheles Stephensi ◽

Vaccine Candidate ◽

Transmission Blocking ◽

Blocking Activity ◽

Malaria Vaccine Candidate

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Antibodies to Malaria Vaccine Candidates Pvs25 and Pvs28 Completely Block the Ability of Plasmodium vivax To Infect Mosquitoes

Infection and Immunity ◽

10.1128/iai.68.12.6618-6623.2000 ◽

2000 ◽

Vol 68 (12) ◽

pp. 6618-6623 ◽

Cited By ~ 111

Author(s):

Hajime Hisaeda ◽

Anthony W. Stowers ◽

Takafumi Tsuboi ◽

William E. Collins ◽

Jetsumon S. Sattabongkot ◽

...

Keyword(s):

Plasmodium Vivax ◽

Malaria Vaccine ◽

Antibody Responses ◽

Sexual Stage ◽

Infected Blood ◽

Transmission Blocking ◽

Vaccine Candidates ◽

Human Antibodies ◽

Transmission Blocking Vaccines ◽

Transmission Blocking Vaccine

ABSTRACT Transmission-blocking vaccines are one strategy for controlling malaria, whereby sexual-stage parasites are inhibited from infecting mosquitoes by human antibodies. To evaluate whether the recently clonedPlasmodium vivax proteins Pvs25 and Pvs28 are candidates for a transmission-blocking vaccine, the molecules were expressed in yeast as secreted recombinant proteins. Mice vaccinated with these proteins adsorbed to aluminum hydroxide developed strong antibody responses against the immunogens, although for Pvs28, this response was genetically restricted. Antisera against both recombinant Pvs25 and Pvs28 recognized the corresponding molecules expressed by cultured sexual-stage parasites isolated from patients with P. vivaxmalaria. The development of malaria parasites in mosquitoes was completely inhibited when these antisera were ingested with the infected blood meal. Pvs25 and Pvs28, expressed inSaccharomyces cerevisiae, are as yet the only fully characterized transmission-blocking vaccine candidates against P. vivax that induce such a potent antiparasite response.

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The use of transgenic Plasmodium berghei expressing the Plasmodium vivax antigen P25 to determine the transmission-blocking activity of sera from malaria vaccine trials

Vaccine ◽

10.1016/j.vaccine.2006.09.035 ◽

2007 ◽

Vol 25 (5) ◽

pp. 886-894 ◽

Cited By ~ 35

Author(s):

Souraya Ramjanee ◽

James S. Robertson ◽

Blandine Franke-Fayard ◽

Ria Sinha ◽

Andrew P. Waters ◽

...

Keyword(s):

Plasmodium Vivax ◽

Plasmodium Berghei ◽

Malaria Vaccine ◽

Transmission Blocking ◽

Vaccine Trials ◽

Blocking Activity

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In vitro antimalarial interaction and transmission-blocking activity of cryptolepine

Planta Medica ◽

10.1055/s-0036-1596329 ◽

2016 ◽

Vol 81 (S 01) ◽

pp. S1-S381

Author(s):

A Donkor Forkuo ◽

C Ansah ◽

B Gyan ◽

D Mancama ◽

A Theron

Keyword(s):

Transmission Blocking ◽

Blocking Activity

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In silico characterisation of putative Plasmodium falciparum vaccine candidates in African malaria populations

Scientific Reports ◽

10.1038/s41598-021-95442-4 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

O. Ajibola ◽

M. F. Diop ◽

A. Ghansah ◽

L. Amenga-Etego ◽

L. Golassa ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Malaria Vaccine ◽

Transmembrane Domain ◽

Vaccine Development ◽

Balancing Selection ◽

Immune Recognition ◽

African Countries ◽

Vaccine Candidates ◽

D Values ◽

Tajima’S D

AbstractGenetic diversity of surface exposed and stage specific Plasmodium falciparum immunogenic proteins pose a major roadblock to developing an effective malaria vaccine with broad and long-lasting immunity. We conducted a prospective genetic analysis of candidate antigens (msp1, ama1, rh5, eba175, glurp, celtos, csp, lsa3, Pfsea, trap, conserved chrom3, hyp9, hyp10, phistb, surfin8.2, and surfin14.1) for malaria vaccine development on 2375 P. falciparum sequences from 16 African countries. We described signatures of balancing selection inferred from positive values of Tajima’s D for all antigens across all populations except for glurp. This could be as a result of immune selection on these antigens as positive Tajima’s D values mapped to regions with putative immune epitopes. A less diverse phistb antigen was characterised with a transmembrane domain, glycophosphatidyl anchors between the N and C- terminals, and surface epitopes that could be targets of immune recognition. This study demonstrates the value of population genetic and immunoinformatic analysis for identifying and characterising new putative vaccine candidates towards improving strain transcending immunity, and vaccine efficacy across all endemic populations.

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