Randomized, Controlled Phase II Clinical Trial to Evaluate the Safety, Immunogenicity and Efficacy of the AMA-1 Malaria Vaccine FMP2.1/AS02A Versus Rabies Vaccine in 1-6 Year Old Children in Bandiagara, Mali

Malaria is a disease that affects many people in Africa. Malaria is caused by germs spread by mosquito bites. The purpose of this study is to compare the number of children who get malaria after receiving an experimental malaria vaccine (FMP2.1/AS02A) to the number of children who get malaria after receiving a vaccine for rabies (an approved vaccine that does not prevent malaria). The children will be assigned to one of the vaccine groups by chance. Participants and doctors will not know which vaccine was given. Study participants will include 400 children, ages 1-6 years, living in Bandiagara, Mali. Children will receive 3 vaccine doses, by injection, to their upper arm. Study procedures will include physical exams and several blood samples. Participants will be involved in the study for 26 months.

Start Date01 May 2007

Sponsor / Collaborator

U S Army Medical Research & Development Command

[+4]

NCT00358332

/ CompletedPhase 1IIT

Randomized, Controlled, Dose Escalation Phase I Clinical Trial to Evaluate the Safety and Immunogenicity of WRAIR's AMA-1 Malaria Vaccine (FMP2.1) Adjuvanted in GSKBio's AS02A Vs. Rabies Vaccine in 1-6 Year Old Children in Bandiagara, Mali

The purpose of this study is to test the safety and dosages of a malaria vaccine in 100 children, 1-6 years old, in Bandiagara, Mali. The study is testing the safety of the vaccine when it is given to people who are regularly exposed to malaria and it will provide information regarding optimal vaccine dosage. This study will compare 3 injections of different vaccine doses to a rabies vaccine that is already approved. During the study, the child's health will be checked in the clinic and during home visits. Children may participate for about 14 months, and blood will be taken from each child throughout the study. If the child becomes sick from malaria, he/she will be treated. Information from this study may be used to develop a malaria vaccine that will help control the disease.

Start Date01 Nov 2006

Sponsor / Collaborator

U S Army Medical Research & Development Command

[+4]

NCT00385047

/ CompletedPhase 1/2IIT

Phase I/IIa Study of the Safety, Immunogenicity and Preliminary Efficacy After Sporozoite Challenge of FMP2.1/AS01B and FMP2.1/AS02A Candidate Malaria Vaccines Administered Intramuscularly at Months 0, 1, and 2 in Malaria-naive Adults Living in the United States

The purpose of this study is to determine whether 2 investigational malaria vaccines are safe as well as protective against malaria in adults living in the United States

Start Date01 Sep 2006

Sponsor / Collaborator

U S Army Medical Research & Development Command

[+2]

100 Clinical Results associated with FMP 2.1 malaria vaccine(Walter Reed Army Institute of Research)

100 Translational Medicine associated with FMP 2.1 malaria vaccine(Walter Reed Army Institute of Research)

100 Patents (Medical) associated with FMP 2.1 malaria vaccine(Walter Reed Army Institute of Research)

Literatures (Medical) associated with FMP 2.1 malaria vaccine(Walter Reed Army Institute of Research)

01 Jul 2020·Vaccine

Epitope-based sieve analysis of Plasmodium falciparum sequences from a FMP2.1/AS02A vaccine trial is consistent with differential vaccine efficacy against immunologically relevant AMA1 variants

Article

Author: Laurens, Matthew B ; Niangaly, Amadou ; Kone, Abdoulaye K ; Thera, Mahamadou A ; Takala-Harrison, Shannon ; Djimdé, Abdoulaye ; Tolo, Youssouf ; Coulibaly, Drissa ; Adams, Matthew ; Doumbo, Ogobara K ; Diallo, Dapa A ; Plowe, Christopher V ; Laufer, Miriam K ; Kouriba, Bourema ; Silva, Joana C ; Ouattara, Amed ; Traore, Karim

To prevent premature dismissal of promising vaccine programs, it is critical to determine if lack of efficacy in the field is due to allele specific-efficacy, rather than to the lack of immunogenicity of the candidate antigen. Here we use samples collected during a field trial of the AMA1-based FMP2.1/AS02_A malaria vaccine, which incorporates the AMA1 variant encoded by the reference Plasmodium falciparum 3D7 strain, to assess the usefulness of epitope-based sieve analysis for the detection of vaccine-induced allele-specific immune responses. The samples used are from volunteers who received the malaria vaccine FMP2.1/AS02_A or a control (rabies vaccine), during a vaccine efficacy field trial, and who later developed malaria. In a previous study, P. falciparum DNA was extracted from all samples, and the ama1 locus amplified and sequenced. Here, a sieve analysis was used to measure T and B-cell escape, and difference in 3D7-like epitopes in the two treatment arms. Overall, no difference was observed in mean amino acid distance to the 3D7 AMA1 variant between sequences from vaccinees and controls in B-cell epitopes. However, we found a significantly greater proportion of 3D7-like T-cell epitopes that map to the AMA1 cluster one loop (c1L) region in the control vs. the vaccinee group (p = 0.02), consistent with allele-specific vaccine efficacy. Interestingly, AMA1 epitopes in infections from vaccinees had higher mean IC50, and consequently lower binding affinity, than epitopes generated from the control group (p = 0.01), suggesting that vaccine-induced selection impacted the immunological profile of the strains that pass through the sieve imposed by the vaccine-induced protection. These findings are consistent with a vaccine-derived sieve effect on the c1L region of AMA1 and suggest that sieve analyses of malaria vaccine trial samples targeted to epitopes identified in silico can help identify protective malaria antigens that may be efficacious if combined in a multivalent vaccine.

01 Dec 2019·Malaria JournalQ3 · MEDICINE

Immunoglobulin G subclass and antibody avidity responses in Malian children immunized with Plasmodium falciparum apical membrane antigen 1 vaccine candidate FMP2.1/AS02A

Q3 · MEDICINE

ArticleOA

Author: Dutta, Sheetij ; Berry, Andrea A ; Diggs, Carter L ; Niangaly, Amadou ; Plowe, Christopher V ; Ouattara, Amed ; Laurens, Matthew B ; Coulibaly, Drissa ; Thera, Mahamadou A ; Gottlieb, Eric R ; Tolo, Youssouf ; Traore, Karim ; Sztein, Marcelo B ; Doumbo, Ogobara K ; Kone, Abdoulaye K ; Lyke, Kirsten E ; Kouriba, Bourema ; Mishcherkin, Vladimir ; Soisson, Lorraine ; Blackwelder, William C ; Diarra, Issa

BACKGROUNDA malaria vaccine based on Plasmodium falciparum apical membrane antigen 1 (AMA1) elicited strain specific efficacy in Malian children that waned in the second season after vaccination despite sustained AMA1 antibody titers. With the goal of identifying a humoral correlate of vaccine-induced protection, pre- and post-vaccination sera from children vaccinated with the AMA1 vaccine and from a control group that received a rabies vaccine were tested for AMA1-specific immunoglobulin G (IgG) subclasses (IgG1, IgG2, IgG3, and IgG4) and for antibody avidity.METHODSSamples from a previously completed Phase 2 AMA1 vaccine trial in children residing in Mali, West Africa were used to determine AMA1-specific IgG subclass antibody titers and avidity by ELISA. Cox proportional hazards models were used to assess correlation between IgG subclass antibody titers and risk of time to first or only clinical malaria episode and risk of multiple episodes. Asexual P. falciparum parasite density measured for each child as area under the curve were used to assess correlation between IgG subclass antibody titers and parasite burden.RESULTSAMA1 vaccination did not elicit a change in antibody avidity; however, AMA1 vaccinees had a robust IgG subclass response that persisted over the malaria transmission season. AMA1-specific IgG subclass responses were not associated with decreased risk of subsequent clinical malaria. For the AMA1 vaccine group, IgG3 levels at study day 90 correlated with high parasite burden during days 90-240. In the control group, AMA1-specific IgG subclass rise and persistence over the malaria season was modest and correlated with age. In the control group, titers of several IgG subclasses at days 90 and 240 correlated with parasite burden over the first 90 study days, and IgG3 at day 240 correlated with parasite burden during days 90-240.CONCLUSIONSNeither IgG subclass nor avidity was associated with the modest, strain-specific efficacy elicited by this blood stage malaria vaccine. Although a correlate of protection was not identified, correlations between subclass titers and age, and correlations between IgG subclass titers and parasite burden, defined by area under the curve parasitaemia levels, were observed, which expand knowledge about IgG subclass responses. IgG3, known to have the shortest half-life of the IgG subclasses, might be the most temporally relevant indicator of ongoing malaria exposure when examining antibody responses to AMA1.

01 Jun 2016·Journal of Infectious DiseasesQ2 · MEDICINE

Demonstration of the Blood-StagePlasmodium falciparumControlled Human Malaria Infection Model to Assess Efficacy of theP. falciparumApical Membrane Antigen 1 Vaccine, FMP2.1/AS01

Q2 · MEDICINE

Article

Author: Ockenhouse, Christian F ; Sukhtankar, Priya ; de Graaf, Hans ; Elias, Sean C ; Halstead, Fenella D ; Nugent, Fay L ; McCarthy, James S ; Birkett, Ashley J ; Hill, Adrian V S ; Douglas, Alexander D ; Woods, Colleen ; Venkatraman, Navin ; Kathcart, April K ; Hodgson, Susanne H ; Rampling, Thomas W ; Miura, Kazutoyo ; Silk, Sarah E ; Williams, Nicola C ; Milne, Kathryn H ; Edwards, Nick J ; Ivinson, Karen ; Vekemans, Johan ; Faust, Saul N ; Lawrie, Alison M ; Brown, Rebecca E ; Cooke, Graham S ; Diggs, Carter L ; Dutta, Sheetij ; Poulton, Ian D ; Payne, Ruth O ; Roberts, Rachel ; Waters, Norman C ; Draper, Simon J ; Labbé, Geneviève M ; Qabar, Aziz N ; Biswas, Sumi ; Long, Carole A ; Soisson, Lorraine A

BACKGROUNDModels of controlled human malaria infection (CHMI) initiated by mosquito bite have been widely used to assess efficacy of preerythrocytic vaccine candidates in small proof-of-concept phase 2a clinical trials. Efficacy testing of blood-stage malaria parasite vaccines, however, has generally relied on larger-scale phase 2b field trials in malaria-endemic populations. We report the use of a blood-stage P. falciparum CHMI model to assess blood-stage vaccine candidates, using their impact on the parasite multiplication rate (PMR) as the primary efficacy end point.METHODSFifteen healthy United Kingdom adult volunteers were vaccinated with FMP2.1, a protein vaccine that is based on the 3D7 clone sequence of apical membrane antigen 1 (AMA1) and formulated in Adjuvant System 01 (AS01). Twelve vaccinees and 15 infectivity controls subsequently underwent blood-stage CHMI. Parasitemia was monitored by quantitative real-time polymerase chain reaction (PCR) analysis, and PMR was modeled from these data.RESULTSFMP2.1/AS01 elicited anti-AMA1 T-cell and serum antibody responses. Analysis of purified immunoglobulin G showed functional growth inhibitory activity against P. falciparum in vitro. There were no vaccine- or CHMI-related safety concerns. All volunteers developed blood-stage parasitemia, with no impact of the vaccine on PMR.CONCLUSIONSFMP2.1/AS01 demonstrated no efficacy after blood-stage CHMI. However, the model induced highly reproducible infection in all volunteers and will accelerate proof-of-concept testing of future blood-stage vaccine candidates.CLINICAL TRIALS REGISTRATIONNCT02044198.

100 Deals associated with FMP 2.1 malaria vaccine(Walter Reed Army Institute of Research)

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Malaria, Falciparum	Phase 2	Mali	GSK Plc	01 May 2007
Malaria, Falciparum	Phase 2	Mali	Walter Reed Army Institute of Research	01 May 2007
Malaria	Phase 2	-	National Institute of Allergy & Infectious Diseases	-
Malaria	Phase 2	-	United States Army Medical Research and Materiel Command	-
Malaria	Phase 2	-	University of Maryland	-

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00460525 (CTgov)	Phase 2	Malaria, Falciparum	400	Rabies Vaccine (Rabies Vaccine)	(qxpjgjdxgq) = qmyhrejuoi ysedmdxqdk (fivjbzlzty, pgvkfclsph - eprrghedur) View more	-	10 Aug 2010
				FMP2.1/AS02A (FMP2.1/AS02A)	(qxpjgjdxgq) = wptgflriif ysedmdxqdk (fivjbzlzty, zmeijrcgzu - ofquxwvqym) View more
NCT00358332 (CTgov)	Phase 1	Malaria, Falciparum	100	thimerosal+FMP2.1/AS02A (FMP2.1/AS02A 10 Mcg)	(aqfxkzxhre) = chycthhcwf hcnutvexxi (gulgfwwgqw, fcsshasgff - minevwbmut) View more	-	04 Mar 2009
				FMP2+thimerosal (FMP2.1/AS02A 25 Mcg)	(aqfxkzxhre) = rhvlnabqxf hcnutvexxi (gulgfwwgqw, gcowxxupgz - uvyzefbyel) View more
NCT00385047 (Pubmed \| J Biol Chem)	Phase 1/2	Malaria	30	apical membrane antigen-1 (AMA-1) (AMA-1/AS01B)	hywusmtaqv(ojtajeuxop) = xtmfosjfyc fgvizgbiof (vbnmprywlz, 210 - 369)	-	01 Jan 2009
				apical membrane antigen-1 (AMA-1) (AMA-1/AS02A)	hywusmtaqv(ojtajeuxop) = gzwfoahymd fgvizgbiof (vbnmprywlz, 169 - 276)

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis

FMP 2.1 malaria vaccine(Walter Reed Army Institute of Research)

Overview

Basic Info

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation