A Plant-Produced Pfs25 VLP Malaria Vaccine Candidate Induces Persistent Transmission Blocking Antibodies against Plasmodium falciparum in Immunized Mice

Q3 · CROSS-FIELD

ArticleOA

Author: Stephen J. Streatfield ; Louis J. Casta ; Jennifer Jaje ; Stephen Tottey ; Jessica A. Chichester ; Joey Norikane ; Slobodanka Manceva ; Marga van de Vegte-Bolmer ; Valentina Mett ; Sandra K. Gibbs ; Moneim Shamloul ; Robert W. Sauerwein ; Will Roeffen ; R. Mark Jones ; Konstantin Musiychuk ; Vidadi Yusibov ; Vadim Mett

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.

npj Vaccines

A Pvs25 mRNA vaccine induces complete and durable transmission-blocking immunity to Plasmodium vivax

Article

Author: Nguitragool, Wang ; Takashima, Eizo ; Ishino, Tomoko ; Tsuboi, Takafumi ; Tam, Ying K ; Pichyangkul, Sathit ; Lin, Paulo J C ; Kangwanrangsan, Niwat ; Pardi, Norbert ; Muramatsu, Hiromi ; Kunkeaw, Nawapol ; Sattabongkot, Jetsumon ; Tachibana, Mayumi

AbstractPlasmodium vivax (P. vivax) is the major malaria parasite outside of Africa and no vaccine is available against it. A vaccine that interrupts parasite transmission (transmission-blocking vaccine, TBV) is considered highly desirable to reduce the spread of P. vivax and to accelerate its elimination. However, the development of a TBV against this pathogen has been hampered by the inability to culture the parasite as well as the low immunogenicity of the vaccines developed to date. Pvs25 is the most advanced TBV antigen candidate for P. vivax. However, in previous phase I clinical trials, TBV vaccines based on Pvs25 yielded low antibody responses or had unacceptable safety profiles. As the nucleoside-modified mRNA–lipid nanoparticle (mRNA–LNP) vaccine platform proved to be safe and effective in humans, we generated and tested mRNA–LNP vaccines encoding several versions of Pvs25 in mice. We found that in a prime-boost vaccination schedule, all Pvs25 mRNA–LNP vaccines elicited robust antigen-specific antibody responses. Furthermore, when compared with a Pvs25 recombinant protein vaccine formulated with Montanide ISA-51 adjuvant, the full-length Pvs25 mRNA–LNP vaccine induced a stronger and longer-lasting functional immunity. Seven months after the second vaccination, vaccine-induced antibodies retained the ability to fully block P. vivax transmission in direct membrane feeding assays, whereas the blocking activity induced by the protein/ISA-51 vaccine dropped significantly. Taken together, we report on mRNA vaccines targeting P. vivax and demonstrate that Pvs25 mRNA–LNP outperformed an adjuvanted Pvs25 protein vaccine suggesting that it is a promising candidate for further testing in non-human primates.

npj Vaccines

mRNA-LNP expressing PfCSP and Pfs25 vaccine candidates targeting infection and transmission of Plasmodium falciparum

Article

Author: Tam, Ying K ; Weissman, Drew ; Zavala, Fidel ; Hayashi, Clifford T H ; Alameh, Mohamad-Gabriel ; Lin, Paulo J C ; Tripathi, Abhai K ; Kumar, Nirbhay ; Cao, Yi ; Clark, Leor C ; Dwivedi, Garima ; Knox, James

AbstractMalaria is a deadly disease responsible for between 550,000 and 627,000 deaths annually. There is a pressing need to develop vaccines focused on malaria elimination. The complex lifecycle of Plasmodium falciparum provides opportunities not only to target the infectious sporozoite stage, introduced by anopheline mosquitoes, but also the sexual stages, which are ingested by mosquitoes during blood feeding, leading to parasite transmission. It is widely recognized that a vaccine targeting multiple stages would induce efficacious transmission reducing immunity. Technological advancements offer new vaccine platforms, such as mRNA-LNPs, which can be used to develop highly effective malarial vaccines. We evaluated the immunogenicity of two leading P. falciparum vaccine candidates, Pfs25 and PfCSP, delivered as mRNA-LNP vaccines. Both vaccines induced extremely potent immune responses when administered alone or in combination, which were superior to Pfs25 and PfCSP DNA vaccine formulations. Purified IgGs from Pfs25 mRNA-LNPs immunized mice were highly potent in reducing malaria transmission to mosquitoes. Additionally, mice after three and four immunizations with PfCSP mRNA-LNP provided evidence for varying degrees of protection against sporozoite challenge. The comparison of immune responses and stage-specific functional activity induced by each mRNA-LNP vaccine, administered alone or in combination, also supports the development of an effective combination vaccine without any risk of immune interference for targeting malaria parasites at various life cycle stages. A combination of vaccines targeting both the infective stage and sexual/midgut stages is expected to interrupt malaria transmission, which is critical for achieving elimination goals.

100 Deals associated with Pfs25 mRNA-LNP(University of Washington/Acuitas Therapeutics/The Johns Hopkins University)

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Indication	Highest Phase	Country/Location	Organization	Date
Malaria	Preclinical	-	The Johns Hopkins University	01 Dec 2022
Malaria	Preclinical	-	Acuitas Therapeutics, Inc.	01 Dec 2022
Malaria	Preclinical	-	University of Washington	01 Dec 2022

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Pfs25 mRNA-LNP(University of Washington/Acuitas Therapeutics/The Johns Hopkins University)

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