Phase 1 clinical trial of apical membrane antigen 1: An asexual blood-stage vaccine for Plasmodium falciparum malaria

Elissa M. Malkin, David J. Diemert, Julie H. McArthur, John R. Perreault, Aaron P. Miles, Birgitte K. Giersing, Gregory E. Mullen, Andrew Orcutt, Olga Muratova, May Awkal, Hong Zhou, Jin Wang, Anthony Stowers, Carole A. Long, Siddhartha Mahanty, Louis H. Miller, Allan Saul, Anna P Durbin

Research output: Contribution to journalArticle

Abstract

Apical membrane antigen 1 (AMA1), a polymorphic merozoite surface protein, is a leading blood-stage malaria vaccine candidate. A phase 1 trial was conducted with 30 malaria-naïve volunteers to assess the safety and immunogenicity of the AMA1-C1 malaria vaccine. AMA1-C1 contains an equal mixture of recombinant proteins based on sequences from the FVO and 3D7 clones of Plasmodium falciparum. The proteins were expressed in Pichia pastoris and adsorbed on Alhydrogel. Ten volunteers in each of three dose groups (5 μg, 20 μg, and 80 μg) were vaccinated in an open-label study at 0, 28, and 180 days. The vaccine was well tolerated, with pain at the injection site being the most commonly observed reaction. Anti-AMA1 immunoglobulin G (IgG) was detected by enzyme-linked immunosorbent assay (ELISA) in 15/28 (54%) volunteers after the second immunization and in 23/25 (92%) after the third immunization, with equal reactivity to both AMA1-FVO and AMA1-3D7 vaccine components. A significant dose-response relationship between antigen dose and antibody response by ELISA was observed, and the antibodies were predominantly of the IgG1 isotype. Confocal microscopic evaluation of sera from vaccinated volunteers demonstrated reactivity with P. falciparum schizonts in a pattern similar to native parasite AMA1. Antigen-specific in vitro inhibition of both FVO and 3D7 parasites was achieved with IgG purified from sera of vaccinees, demonstrating biological activity of the antibodies. To our knowledge, this is the first AMA1 vaccine candidate to elicit functional immune responses in malaria-naïve humans, and our results support the further development of this vaccine.

Original languageEnglish (US)
Pages (from-to)3677-3685
Number of pages9
JournalInfection and Immunity
Volume73
Issue number6
DOIs
StatePublished - Jun 2005

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Clinical Trials, Phase I
Falciparum Malaria
Vaccines
Antigens
Membranes
Volunteers
Malaria Vaccines
Immunoglobulin G
Plasmodium falciparum
Malaria
Immunization
Parasites
Enzyme-Linked Immunosorbent Assay
Schizonts
Aluminum Hydroxide
Merozoites
Pichia
Antibodies
Serum
Recombinant Proteins

ASJC Scopus subject areas

  • Immunology

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Phase 1 clinical trial of apical membrane antigen 1 : An asexual blood-stage vaccine for Plasmodium falciparum malaria. / Malkin, Elissa M.; Diemert, David J.; McArthur, Julie H.; Perreault, John R.; Miles, Aaron P.; Giersing, Birgitte K.; Mullen, Gregory E.; Orcutt, Andrew; Muratova, Olga; Awkal, May; Zhou, Hong; Wang, Jin; Stowers, Anthony; Long, Carole A.; Mahanty, Siddhartha; Miller, Louis H.; Saul, Allan; Durbin, Anna P.

In: Infection and Immunity, Vol. 73, No. 6, 06.2005, p. 3677-3685.

Research output: Contribution to journalArticle

Malkin, EM, Diemert, DJ, McArthur, JH, Perreault, JR, Miles, AP, Giersing, BK, Mullen, GE, Orcutt, A, Muratova, O, Awkal, M, Zhou, H, Wang, J, Stowers, A, Long, CA, Mahanty, S, Miller, LH, Saul, A & Durbin, AP 2005, 'Phase 1 clinical trial of apical membrane antigen 1: An asexual blood-stage vaccine for Plasmodium falciparum malaria', Infection and Immunity, vol. 73, no. 6, pp. 3677-3685. https://doi.org/10.1128/IAI.73.6.3677-3685.2005
Malkin, Elissa M. ; Diemert, David J. ; McArthur, Julie H. ; Perreault, John R. ; Miles, Aaron P. ; Giersing, Birgitte K. ; Mullen, Gregory E. ; Orcutt, Andrew ; Muratova, Olga ; Awkal, May ; Zhou, Hong ; Wang, Jin ; Stowers, Anthony ; Long, Carole A. ; Mahanty, Siddhartha ; Miller, Louis H. ; Saul, Allan ; Durbin, Anna P. / Phase 1 clinical trial of apical membrane antigen 1 : An asexual blood-stage vaccine for Plasmodium falciparum malaria. In: Infection and Immunity. 2005 ; Vol. 73, No. 6. pp. 3677-3685.
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AU - Mullen, Gregory E.

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AU - Zhou, Hong

AU - Wang, Jin

AU - Stowers, Anthony

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