Phase I safety and immunogenicity trial of FMP1/AS02A, a Plasmodium falciparum MSP-1 asexual blood stage vaccine

Christian F Ockenhouse; Evelina Angov; Kent E Kester; Carter Diggs; Lorraine Soisson; James F Cummings; Ann V Stewart; Dupeh R Palmer; Babita Mahajan; Urszula Krzych; Nadia Tornieporth; M Delchambre; M Vanhandenhove; Opokua Ofori-Anyinam; Joe Cohen; Jeffrey A Lyon; D Gray Heppner; MSP-1 Working Group

doi:10.1016/j.vaccine.2005.11.028

Phase I safety and immunogenicity trial of FMP1/AS02A, a Plasmodium falciparum MSP-1 asexual blood stage vaccine

Vaccine. 2006 Apr 5;24(15):3009-17. doi: 10.1016/j.vaccine.2005.11.028. Epub 2005 Nov 28.

Authors

Christian F Ockenhouse¹, Evelina Angov, Kent E Kester, Carter Diggs, Lorraine Soisson, James F Cummings, Ann V Stewart, Dupeh R Palmer, Babita Mahajan, Urszula Krzych, Nadia Tornieporth, M Delchambre, M Vanhandenhove, Opokua Ofori-Anyinam, Joe Cohen, Jeffrey A Lyon, D Gray Heppner; MSP-1 Working Group

Affiliation

¹ Department of Immunology, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA. [email protected]

PMID: 16356603
DOI: 10.1016/j.vaccine.2005.11.028

Abstract

We report the first safety and immunogenicity trial of the Plasmodium falciparum malaria blood stage vaccine candidate, FMP1/AS02A consisting of the FMP1 antigen, an Escherichia coli-expressed His-tagged fusion protein from the 42 kDa C-terminal fragment from the 3D7 clone of the merozoite surface protein 1 formulated in the AS02A adjuvant. An open label, prospective, single-center Phase I dose escalation trial of FMP1/AS02A was conducted in 15 adult malaria-naïve human volunteers to assess safety, reactogenicity, and immunogenicity. The vaccine was safe and well-tolerated and no serious adverse events were observed. The vaccine induced high-titer ELISA and IFA responses in all volunteers. Proliferative and ELISPOT responses were induced to vaccine antigen. Biologically active antibodies were induced as measured by GIA. This study establishes the foundation to further evaluate and measure the vaccine's ability to reduce morbidity and mortality in target populations directly affected by P. falciparum malaria.

Publication types

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

MeSH terms

Adjuvants, Immunologic / administration & dosage
Adjuvants, Immunologic / pharmacology
Adolescent
Adult
Animals
Antibodies, Protozoan / blood
Drug Combinations
Enzyme-Linked Immunosorbent Assay
Female
Fluorescent Antibody Technique, Indirect
Humans
Interferon-gamma / biosynthesis
L-Lactate Dehydrogenase / analysis
Lipid A / administration & dosage
Lipid A / analogs & derivatives*
Lipid A / pharmacology
Malaria Vaccines / administration & dosage
Malaria Vaccines / adverse effects
Malaria Vaccines / immunology*
Male
Merozoite Surface Protein 1 / immunology*
Middle Aged
Plasmodium falciparum / growth & development
Plasmodium falciparum / immunology*
Saponins / administration & dosage
Saponins / pharmacology*
T-Lymphocytes / immunology
Vaccines, Subunit / administration & dosage
Vaccines, Subunit / adverse effects
Vaccines, Subunit / immunology
Vaccines, Synthetic / administration & dosage
Vaccines, Synthetic / adverse effects
Vaccines, Synthetic / immunology

Substances

ASO2A adjuvant
Adjuvants, Immunologic
Antibodies, Protozoan
Drug Combinations
Lipid A
Malaria Vaccines
Merozoite Surface Protein 1
Saponins
Vaccines, Subunit
Vaccines, Synthetic
Interferon-gamma
L-Lactate Dehydrogenase