Safety and immunogenicity of a plant-produced Pfs25 virus-like particle as a transmission blocking vaccine against malaria: A Phase 1 dose-escalation study in healthy adults

Jessica A Chichester; Brian J Green; R Mark Jones; Yoko Shoji; Kazutoyo Miura; Carole A Long; Cynthia K Lee; Christian F Ockenhouse; Merribeth J Morin; Stephen J Streatfield; Vidadi Yusibov

doi:10.1016/j.vaccine.2018.08.033

Safety and immunogenicity of a plant-produced Pfs25 virus-like particle as a transmission blocking vaccine against malaria: A Phase 1 dose-escalation study in healthy adults

Vaccine. 2018 Sep 18;36(39):5865-5871. doi: 10.1016/j.vaccine.2018.08.033. Epub 2018 Aug 17.

Affiliations

¹ Fraunhofer USA Inc. Center for Molecular Biotechnology, Newark, DE 19711, USA.
² Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.
³ PATH's Malaria Vaccine Initiative, Washington, DC 20001, USA.
⁴ Fraunhofer USA Inc. Center for Molecular Biotechnology, Newark, DE 19711, USA. Electronic address: Vidadi.Yusibov@fhcmb.org.

Abstract

Malaria continues to be one of the world's most devastating infectious tropical diseases, and alternative strategies to prevent infection and disease spread are urgently needed. These strategies include the development of effective vaccines, such as malaria transmission blocking vaccines (TBV) directed against proteins found on the sexual stages of Plasmodium falciparum parasites present in the mosquito midgut. The Pfs25 protein, which is expressed on the surface of gametes, zygotes and ookinetes, has been a primary target for TBV development. One such vaccine strategy based on Pfs25 is a plant-produced malaria vaccine candidate engineered as a chimeric non-enveloped virus-like particle (VLP) comprising Pfs25 fused to the Alfalfa mosaic virus coat protein. This Pfs25 VLP-FhCMB vaccine candidate has been engineered and manufactured in Nicotiana benthamiana plants at pilot plant scale under current Good Manufacturing Practice guidelines. The safety, reactogenicity and immunogenicity of Pfs25 VLP-FhCMB was assessed in healthy adult volunteers. This Phase 1, dose escalation, first-in-human study was designed primarily to evaluate the safety of the purified plant-derived Pfs25 VLP combined with Alhydrogel® adjuvant. At the doses tested in this Phase 1 study, the vaccine was generally shown to be safe in healthy volunteers, with no incidence of vaccine-related serious adverse events and no evidence of any dose-limiting or dose-related toxicity, demonstrating that the plant-derived Pfs25 VLP-FhCMB vaccine had an acceptable safety and tolerability profile. In addition, although the vaccine did induce Pfs25-specific IgG in vaccinated patients in a dose dependent manner, the transmission reducing activity of the antibodies generated were weak, suggesting the need for an alternative vaccine adjuvant formulation. This study was registered at www.ClinicalTrials.gov under reference identifier NCT02013687.

Keywords: Malaria; Pfs25; Plant-produced; Transmission blocking vaccine; Virus-like particle.

Publication types

Clinical Trial, Phase I
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't

MeSH terms

Adjuvants, Immunologic / administration & dosage
Adolescent
Adult
Alfalfa mosaic virus
Antibodies, Protozoan / blood
Antigens, Protozoan / immunology
Female
Healthy Volunteers
Humans
Immunogenicity, Vaccine*
Malaria Vaccines / adverse effects
Malaria Vaccines / immunology*
Malaria, Falciparum / prevention & control
Male
Middle Aged
Nicotiana / metabolism
Plasmodium falciparum
Protozoan Proteins / immunology*
Vaccines, Synthetic / adverse effects
Vaccines, Synthetic / immunology*
Vaccines, Virus-Like Particle / immunology*
Young Adult

Substances

Adjuvants, Immunologic
Antibodies, Protozoan
Antigens, Protozoan
Malaria Vaccines
Pfs25 protein, Plasmodium falciparum
Protozoan Proteins
Vaccines, Synthetic
Vaccines, Virus-Like Particle

Associated data

ClinicalTrials.gov/NCT02013687