AA Holder

AE Dent

AR Dluzewski

AW Stowers

B Genton

BA Okech

Ben Andagalu

Bernhards Ogutu

BR Ogutu

Brent House

CA Darko

Carter Diggs

CD Galamo

CF Ockenhouse

Christian F Ockenhouse

D Courtin

D Gray Heppner

DG Heppner Jr

Donna Tosh

E Angov

E Malkin

Elke Bergmann-Leitner

ES Bergmann-Leitner

Evelina Angov

Farhat Khan

FJ McCallum

Godfrey Allan Otieno

GS Hui

JA Lyon

JA Stoute

James Cummings

Jason Bennett

JF Cummings

Joe Cohen

John Waitumbi

KE Kester

KE Persson

L Renia

Lisa Ware

Lori Miller

Lorraine Soisson

Lucas Otieno

MA Thera

Margaret Koech

Marie-Claude Dubois

Mark Polhemus

MD Spring

ME Polhemus

Meng Shi

Michele D Spring

MR Withers

Nancy Richie

Nekoye Otsyula

Olivier Godeaux

PD Crompton

R Perraut

RD Ellis

RI Nwuba

RS McIntosh

RTS,S Clinical Trial Partnership

S Singh

SP Chang

TF De Koning-Ward

V Udhayakumar

W Ripley Ballou

Walter Otieno

Malaria Journal

Abstract
          
            Background
            The development of an asexual blood stage vaccine against Plasmodium falciparum malaria based on the major merozoite surface protein-1 (MSP1) antigen is founded on the protective efficacy observed in preclinical studies and induction of invasion and growth inhibitory antibody responses. The 42 kDa C-terminus of MSP1 has been developed as the recombinant protein vaccine antigen, and the 3D7 allotype, formulated with the Adjuvant System AS02A, has been evaluated extensively in human clinical trials. In preclinical rabbit studies, the FVO allele of MSP142 has been shown to have improved immunogenicity over the 3D7 allele, in terms of antibody titres as well as growth inhibitory activity of antibodies against both the heterologous 3D7 and homologous FVO parasites.
          
          
            Methods
            Two Phase 1 clinical studies were conducted to examine the safety, reactogenicity and immunogenicity of the FVO allele of MSP142 in the adjuvant system AS01 administered intramuscularly at 0-, 1-, and 2-months: one in the USA and, after evaluation of safety data results, one in Western Kenya. The US study was an open-label, dose escalation study of 10 and 50 μg doses of MSP142 in 26 adults, while the Kenya study, evaluating 30 volunteers, was a double-blind, randomized study of only the 50 μg dose with a rabies vaccine comparator.
          
          
            Results
            In these studies it was demonstrated that this vaccine formulation has an acceptable safety profile and is immunogenic in malaria-naïve and malaria-experienced populations. High titres of anti-MSP1 antibodies were induced in both study populations, although there was a limited number of volunteers whose serum demonstrated significant inhibition of blood-stage parasites as measured by growth inhibition assay. In the US volunteers, the antibodies generated exhibited better cross-reactivity to heterologous MSP1 alleles than a MSP1-based vaccine (3D7 allele) previously tested at both study sites.
          
          
            Conclusions
            Given that the primary effector mechanism for blood stage vaccine targets is humoral, the antibody responses demonstrated to this vaccine candidate, both quantitative (total antibody titres) and qualitative (functional antibodies inhibiting parasite growth) warrant further consideration of its application in endemic settings.
          
          
            Trial registrations
            Clinical Trials NCT00666380
          </jats:sec

Crossref

Results from tandem Phase 1 studies evaluating the safety, reactogenicity and immunogenicity of the vaccine candidate antigen Plasmodium falciparum FVO merozoite surface protein-1 (MSP142) administered intramuscularly with adjuvant system AS01

https://malariajournal.biomedcentral.com/track/pdf/10.1186/1475-2875-12-29?site=malariajournal.biomedcentral.com

Results from tandem Phase 1 studies evaluating the safety, reactogenicity and immunogenicity of the vaccine candidate antigen Plasmodium falciparum FVO merozoite surface protein-1 (MSP142) administered intramuscularly with adjuvant system AS01

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