Safety and immunogenicity of an AMA-1 malaria vaccine in Malian adults

Results of a phase 1 randomized controlled trial

Mahamadou A. Thera, Ogobara K. Doumbo, Drissa Coulibaly, Dapa A. Diallo, Abdoulaye K. Kone, Ando B. Guindo, Karim Traore, Alassane Dicko, Issaka Sagara, Mahamadou S. Sissoko, Mounirou Baby, Mady Sissoko, Issa Diarra, Amadou Niangaly, Amagana Dolo, Modibo Daou, Sory I. Diawara, D. Gray Heppner, V. Ann Stewart, Evelina Angov & 14 others Elke S. Bergmann-Leitner, David E. Lanar, Sheetij Dutta, Lorraine Soisson, Carter L. Diggs, Amanda Leach, Alex Owusu, Marie Claude Dubois, Joe Cohen, Jason N. Nixon, Aric Gregson, Shannon L. Takala, Kirsten E. Lyke, Christopher V. Plowe

    Research output: Contribution to journalArticleResearchpeer-review

    Abstract

    Background. The objective was to evaluate the safety, reactogenicity and immunogenicity of the AMA-1-based blood-stage malaria vaccine FMP2.1/ AS02A in adults exposed to seasonal malaria. Methodology/Principal Findings. A phase 1 double Wind randomized controlled dose escalation trial was conductected in Bandiagara, Mall, West Africa, a rural town with intense seasonal transmission of Plasmodium falciparum malaria. The malaria vaccine FMP2.1/AS02A is a recombinant protein (FMP2.1) based on apical membrane antigen-1 (AMA-1) from the 3D7 clone of P. falciparum, adjuvanted with AS02A. The comparator vaccine was a cell-culture rabies virus vaccine (RabAvert). Sixty healthy, malaria-experienced adults aged 18-55 y were recruited into 2 cohorts and randomized to receive either a half dose or full dose of the malaria vaccine (FMP2.1 25 μg/A502A 0.25 ml. or FMP2.1 50 μg/AS02a 0.5 ml) or rabies vaccine given in 3 doses at 0, 1 and 2 mo, and were followed for 1 y. Solicited symptoms were assessed for 7 d and unsolicited symptoms for 30 d after each vaccination. Sewious adverse events were assessed throughout the study. Titers of anti-AMA-1 antibodies were measured by ELISA and p. falciparum growth inhibition assays were performed on sera collected at pre- and post-vaccination time points. Transient local pain and swelling were common and more frequent in both malaria vaccine dosage groups than in the comparator group. Anti-AMA-1 antibodies increased significantly in both malaria vaccine groups, peaking at nearly 5-fold and more than 6-foid higher than baseline in the half-dose and full-dose groups, respectively. Conclusion/Significance. The FMP2.1/AS02A vaccine had a good safety profile, was well-talerated, and was highly immunogenic in malaria-exposed adults, This malaria vaccine is being evaluated in Phase 1 and 2 trials in children at this site.

    Original languageEnglish
    Article numbere1465
    Pages (from-to)1-11
    Number of pages11
    JournalPLoS One
    Volume3
    Issue number1
    DOIs
    Publication statusPublished - 2008

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    Malaria Vaccines
    Randomized Controlled Trials
    immune response
    antigens
    Membranes
    Safety
    Antigens
    malaria
    dosage
    Rabies Vaccines
    Malaria
    Vaccination
    vaccines
    Vaccines
    vaccination
    Plasmodium falciparum
    signs and symptoms (animals and humans)
    Rabies virus
    Shopping centers
    Western Africa

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    Thera, M. A., Doumbo, O. K., Coulibaly, D., Diallo, D. A., Kone, A. K., Guindo, A. B., ... Plowe, C. V. (2008). Safety and immunogenicity of an AMA-1 malaria vaccine in Malian adults: Results of a phase 1 randomized controlled trial. PLoS One, 3(1), 1-11. [e1465]. https://doi.org/10.1371/journal.pone.0001465
    Thera, Mahamadou A. ; Doumbo, Ogobara K. ; Coulibaly, Drissa ; Diallo, Dapa A. ; Kone, Abdoulaye K. ; Guindo, Ando B. ; Traore, Karim ; Dicko, Alassane ; Sagara, Issaka ; Sissoko, Mahamadou S. ; Baby, Mounirou ; Sissoko, Mady ; Diarra, Issa ; Niangaly, Amadou ; Dolo, Amagana ; Daou, Modibo ; Diawara, Sory I. ; Heppner, D. Gray ; Stewart, V. Ann ; Angov, Evelina ; Bergmann-Leitner, Elke S. ; Lanar, David E. ; Dutta, Sheetij ; Soisson, Lorraine ; Diggs, Carter L. ; Leach, Amanda ; Owusu, Alex ; Dubois, Marie Claude ; Cohen, Joe ; Nixon, Jason N. ; Gregson, Aric ; Takala, Shannon L. ; Lyke, Kirsten E. ; Plowe, Christopher V. / Safety and immunogenicity of an AMA-1 malaria vaccine in Malian adults : Results of a phase 1 randomized controlled trial. In: PLoS One. 2008 ; Vol. 3, No. 1. pp. 1-11.
    @article{00e0208795b24f3e81c87f7e73a4bc96,
    title = "Safety and immunogenicity of an AMA-1 malaria vaccine in Malian adults: Results of a phase 1 randomized controlled trial",
    abstract = "Background. The objective was to evaluate the safety, reactogenicity and immunogenicity of the AMA-1-based blood-stage malaria vaccine FMP2.1/ AS02A in adults exposed to seasonal malaria. Methodology/Principal Findings. A phase 1 double Wind randomized controlled dose escalation trial was conductected in Bandiagara, Mall, West Africa, a rural town with intense seasonal transmission of Plasmodium falciparum malaria. The malaria vaccine FMP2.1/AS02A is a recombinant protein (FMP2.1) based on apical membrane antigen-1 (AMA-1) from the 3D7 clone of P. falciparum, adjuvanted with AS02A. The comparator vaccine was a cell-culture rabies virus vaccine (RabAvert). Sixty healthy, malaria-experienced adults aged 18-55 y were recruited into 2 cohorts and randomized to receive either a half dose or full dose of the malaria vaccine (FMP2.1 25 μg/A502A 0.25 ml. or FMP2.1 50 μg/AS02a 0.5 ml) or rabies vaccine given in 3 doses at 0, 1 and 2 mo, and were followed for 1 y. Solicited symptoms were assessed for 7 d and unsolicited symptoms for 30 d after each vaccination. Sewious adverse events were assessed throughout the study. Titers of anti-AMA-1 antibodies were measured by ELISA and p. falciparum growth inhibition assays were performed on sera collected at pre- and post-vaccination time points. Transient local pain and swelling were common and more frequent in both malaria vaccine dosage groups than in the comparator group. Anti-AMA-1 antibodies increased significantly in both malaria vaccine groups, peaking at nearly 5-fold and more than 6-foid higher than baseline in the half-dose and full-dose groups, respectively. Conclusion/Significance. The FMP2.1/AS02A vaccine had a good safety profile, was well-talerated, and was highly immunogenic in malaria-exposed adults, This malaria vaccine is being evaluated in Phase 1 and 2 trials in children at this site.",
    author = "Thera, {Mahamadou A.} and Doumbo, {Ogobara K.} and Drissa Coulibaly and Diallo, {Dapa A.} and Kone, {Abdoulaye K.} and Guindo, {Ando B.} and Karim Traore and Alassane Dicko and Issaka Sagara and Sissoko, {Mahamadou S.} and Mounirou Baby and Mady Sissoko and Issa Diarra and Amadou Niangaly and Amagana Dolo and Modibo Daou and Diawara, {Sory I.} and Heppner, {D. Gray} and Stewart, {V. Ann} and Evelina Angov and Bergmann-Leitner, {Elke S.} and Lanar, {David E.} and Sheetij Dutta and Lorraine Soisson and Diggs, {Carter L.} and Amanda Leach and Alex Owusu and Dubois, {Marie Claude} and Joe Cohen and Nixon, {Jason N.} and Aric Gregson and Takala, {Shannon L.} and Lyke, {Kirsten E.} and Plowe, {Christopher V.}",
    year = "2008",
    doi = "10.1371/journal.pone.0001465",
    language = "English",
    volume = "3",
    pages = "1--11",
    journal = "PLoS One",
    issn = "1932-6203",
    publisher = "Public Library of Science (PLoS)",
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    }

    Thera, MA, Doumbo, OK, Coulibaly, D, Diallo, DA, Kone, AK, Guindo, AB, Traore, K, Dicko, A, Sagara, I, Sissoko, MS, Baby, M, Sissoko, M, Diarra, I, Niangaly, A, Dolo, A, Daou, M, Diawara, SI, Heppner, DG, Stewart, VA, Angov, E, Bergmann-Leitner, ES, Lanar, DE, Dutta, S, Soisson, L, Diggs, CL, Leach, A, Owusu, A, Dubois, MC, Cohen, J, Nixon, JN, Gregson, A, Takala, SL, Lyke, KE & Plowe, CV 2008, 'Safety and immunogenicity of an AMA-1 malaria vaccine in Malian adults: Results of a phase 1 randomized controlled trial', PLoS One, vol. 3, no. 1, e1465, pp. 1-11. https://doi.org/10.1371/journal.pone.0001465

    Safety and immunogenicity of an AMA-1 malaria vaccine in Malian adults : Results of a phase 1 randomized controlled trial. / Thera, Mahamadou A.; Doumbo, Ogobara K.; Coulibaly, Drissa; Diallo, Dapa A.; Kone, Abdoulaye K.; Guindo, Ando B.; Traore, Karim; Dicko, Alassane; Sagara, Issaka; Sissoko, Mahamadou S.; Baby, Mounirou; Sissoko, Mady; Diarra, Issa; Niangaly, Amadou; Dolo, Amagana; Daou, Modibo; Diawara, Sory I.; Heppner, D. Gray; Stewart, V. Ann; Angov, Evelina; Bergmann-Leitner, Elke S.; Lanar, David E.; Dutta, Sheetij; Soisson, Lorraine; Diggs, Carter L.; Leach, Amanda; Owusu, Alex; Dubois, Marie Claude; Cohen, Joe; Nixon, Jason N.; Gregson, Aric; Takala, Shannon L.; Lyke, Kirsten E.; Plowe, Christopher V.

    In: PLoS One, Vol. 3, No. 1, e1465, 2008, p. 1-11.

    Research output: Contribution to journalArticleResearchpeer-review

    TY - JOUR

    T1 - Safety and immunogenicity of an AMA-1 malaria vaccine in Malian adults

    T2 - Results of a phase 1 randomized controlled trial

    AU - Thera, Mahamadou A.

    AU - Doumbo, Ogobara K.

    AU - Coulibaly, Drissa

    AU - Diallo, Dapa A.

    AU - Kone, Abdoulaye K.

    AU - Guindo, Ando B.

    AU - Traore, Karim

    AU - Dicko, Alassane

    AU - Sagara, Issaka

    AU - Sissoko, Mahamadou S.

    AU - Baby, Mounirou

    AU - Sissoko, Mady

    AU - Diarra, Issa

    AU - Niangaly, Amadou

    AU - Dolo, Amagana

    AU - Daou, Modibo

    AU - Diawara, Sory I.

    AU - Heppner, D. Gray

    AU - Stewart, V. Ann

    AU - Angov, Evelina

    AU - Bergmann-Leitner, Elke S.

    AU - Lanar, David E.

    AU - Dutta, Sheetij

    AU - Soisson, Lorraine

    AU - Diggs, Carter L.

    AU - Leach, Amanda

    AU - Owusu, Alex

    AU - Dubois, Marie Claude

    AU - Cohen, Joe

    AU - Nixon, Jason N.

    AU - Gregson, Aric

    AU - Takala, Shannon L.

    AU - Lyke, Kirsten E.

    AU - Plowe, Christopher V.

    PY - 2008

    Y1 - 2008

    N2 - Background. The objective was to evaluate the safety, reactogenicity and immunogenicity of the AMA-1-based blood-stage malaria vaccine FMP2.1/ AS02A in adults exposed to seasonal malaria. Methodology/Principal Findings. A phase 1 double Wind randomized controlled dose escalation trial was conductected in Bandiagara, Mall, West Africa, a rural town with intense seasonal transmission of Plasmodium falciparum malaria. The malaria vaccine FMP2.1/AS02A is a recombinant protein (FMP2.1) based on apical membrane antigen-1 (AMA-1) from the 3D7 clone of P. falciparum, adjuvanted with AS02A. The comparator vaccine was a cell-culture rabies virus vaccine (RabAvert). Sixty healthy, malaria-experienced adults aged 18-55 y were recruited into 2 cohorts and randomized to receive either a half dose or full dose of the malaria vaccine (FMP2.1 25 μg/A502A 0.25 ml. or FMP2.1 50 μg/AS02a 0.5 ml) or rabies vaccine given in 3 doses at 0, 1 and 2 mo, and were followed for 1 y. Solicited symptoms were assessed for 7 d and unsolicited symptoms for 30 d after each vaccination. Sewious adverse events were assessed throughout the study. Titers of anti-AMA-1 antibodies were measured by ELISA and p. falciparum growth inhibition assays were performed on sera collected at pre- and post-vaccination time points. Transient local pain and swelling were common and more frequent in both malaria vaccine dosage groups than in the comparator group. Anti-AMA-1 antibodies increased significantly in both malaria vaccine groups, peaking at nearly 5-fold and more than 6-foid higher than baseline in the half-dose and full-dose groups, respectively. Conclusion/Significance. The FMP2.1/AS02A vaccine had a good safety profile, was well-talerated, and was highly immunogenic in malaria-exposed adults, This malaria vaccine is being evaluated in Phase 1 and 2 trials in children at this site.

    AB - Background. The objective was to evaluate the safety, reactogenicity and immunogenicity of the AMA-1-based blood-stage malaria vaccine FMP2.1/ AS02A in adults exposed to seasonal malaria. Methodology/Principal Findings. A phase 1 double Wind randomized controlled dose escalation trial was conductected in Bandiagara, Mall, West Africa, a rural town with intense seasonal transmission of Plasmodium falciparum malaria. The malaria vaccine FMP2.1/AS02A is a recombinant protein (FMP2.1) based on apical membrane antigen-1 (AMA-1) from the 3D7 clone of P. falciparum, adjuvanted with AS02A. The comparator vaccine was a cell-culture rabies virus vaccine (RabAvert). Sixty healthy, malaria-experienced adults aged 18-55 y were recruited into 2 cohorts and randomized to receive either a half dose or full dose of the malaria vaccine (FMP2.1 25 μg/A502A 0.25 ml. or FMP2.1 50 μg/AS02a 0.5 ml) or rabies vaccine given in 3 doses at 0, 1 and 2 mo, and were followed for 1 y. Solicited symptoms were assessed for 7 d and unsolicited symptoms for 30 d after each vaccination. Sewious adverse events were assessed throughout the study. Titers of anti-AMA-1 antibodies were measured by ELISA and p. falciparum growth inhibition assays were performed on sera collected at pre- and post-vaccination time points. Transient local pain and swelling were common and more frequent in both malaria vaccine dosage groups than in the comparator group. Anti-AMA-1 antibodies increased significantly in both malaria vaccine groups, peaking at nearly 5-fold and more than 6-foid higher than baseline in the half-dose and full-dose groups, respectively. Conclusion/Significance. The FMP2.1/AS02A vaccine had a good safety profile, was well-talerated, and was highly immunogenic in malaria-exposed adults, This malaria vaccine is being evaluated in Phase 1 and 2 trials in children at this site.

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    U2 - 10.1371/journal.pone.0001465

    DO - 10.1371/journal.pone.0001465

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    SP - 1

    EP - 11

    JO - PLoS One

    JF - PLoS One

    SN - 1932-6203

    IS - 1

    M1 - e1465

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