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Safety and immunogenicity of an AMA-1 malaria vaccine in Malian adults: results of a phase 1 randomized controlled trial.

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 - PLoS ONE (2008)

Bottom Line: 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-fold higher than baseline in the half-dose and full-dose groups, respectively.The FMP2.1/AS02A vaccine had a good safety profile, was well-tolerated, and was highly immunogenic in malaria-exposed adults.

View Article: PubMed Central - PubMed

Affiliation: Malaria Research and Training Center, University of Bamako, Bamako, Mali.

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 blind randomized controlled dose escalation trial was conducted in Bandiagara, Mali, 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 microg/AS02A 0.25 mL or FMP2.1 50 microg/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. Serious 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-fold 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-tolerated, 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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Related in: MedlinePlus

Anti-AMA-1 antibody titers.Geometric mean antibody titers to homologous recombinant AMA-1 for FMP2.1/AS02A full dose, FMP2.1/AS02A half dose and rabies vaccine recipients. Times of each of three immunizations and the start and end of the malaria transmission season are indicated by triangles. Error bars represent 95 percent confidence intervals.
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pone-0001465-g002: Anti-AMA-1 antibody titers.Geometric mean antibody titers to homologous recombinant AMA-1 for FMP2.1/AS02A full dose, FMP2.1/AS02A half dose and rabies vaccine recipients. Times of each of three immunizations and the start and end of the malaria transmission season are indicated by triangles. Error bars represent 95 percent confidence intervals.

Mentions: Baseline antibody titers were high in all groups (Figure 2), reflecting a high level of naturally acquired immunity at the end of the malaria transmission season. In contrast to the waning antibody titers seen in the rabies vaccine comparator group following the end of the malaria season, immunization with both the half dose and full dose of the malaria vaccine was followed by significant elevations in anti-AMA-1 antibodies. Antibody titers peaked two weeks after the third immunization (study day 74), with a 4.7-fold rise relative to baseline in the malaria vaccine half-dose group and a 6.4-fold rise in the full-dose group. Mean AMA-1 antibody levels remained higher in the malaria vaccine groups than in the comparator group throughout the study period, although confidence intervals for point-wise comparisons overlapped at study time points after day 90. Mean antibody titers were higher in the full-dose group than in the half-dose group at all time points, although these differences were not statistically significant for point-wise comparisons.


Safety and immunogenicity of an AMA-1 malaria vaccine in Malian adults: results of a phase 1 randomized controlled trial.

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 - PLoS ONE (2008)

Anti-AMA-1 antibody titers.Geometric mean antibody titers to homologous recombinant AMA-1 for FMP2.1/AS02A full dose, FMP2.1/AS02A half dose and rabies vaccine recipients. Times of each of three immunizations and the start and end of the malaria transmission season are indicated by triangles. Error bars represent 95 percent confidence intervals.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2186380&req=5

pone-0001465-g002: Anti-AMA-1 antibody titers.Geometric mean antibody titers to homologous recombinant AMA-1 for FMP2.1/AS02A full dose, FMP2.1/AS02A half dose and rabies vaccine recipients. Times of each of three immunizations and the start and end of the malaria transmission season are indicated by triangles. Error bars represent 95 percent confidence intervals.
Mentions: Baseline antibody titers were high in all groups (Figure 2), reflecting a high level of naturally acquired immunity at the end of the malaria transmission season. In contrast to the waning antibody titers seen in the rabies vaccine comparator group following the end of the malaria season, immunization with both the half dose and full dose of the malaria vaccine was followed by significant elevations in anti-AMA-1 antibodies. Antibody titers peaked two weeks after the third immunization (study day 74), with a 4.7-fold rise relative to baseline in the malaria vaccine half-dose group and a 6.4-fold rise in the full-dose group. Mean AMA-1 antibody levels remained higher in the malaria vaccine groups than in the comparator group throughout the study period, although confidence intervals for point-wise comparisons overlapped at study time points after day 90. Mean antibody titers were higher in the full-dose group than in the half-dose group at all time points, although these differences were not statistically significant for point-wise comparisons.

Bottom Line: 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-fold higher than baseline in the half-dose and full-dose groups, respectively.The FMP2.1/AS02A vaccine had a good safety profile, was well-tolerated, and was highly immunogenic in malaria-exposed adults.

View Article: PubMed Central - PubMed

Affiliation: Malaria Research and Training Center, University of Bamako, Bamako, Mali.

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 blind randomized controlled dose escalation trial was conducted in Bandiagara, Mali, 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 microg/AS02A 0.25 mL or FMP2.1 50 microg/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. Serious 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-fold 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-tolerated, 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.

Show MeSH
Related in: MedlinePlus