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Safety and allele-specific immunogenicity of a malaria vaccine in Malian adults: results of a phase I randomized trial.

Thera MA, Doumbo OK, Coulibaly D, Diallo DA, Sagara I, Dicko A, Diemert DJ, Heppner DG, Stewart VA, Angov E, Soisson L, Leach A, Tucker K, Lyke KE, Plowe CV, Mali FMP1 Working Gro - PLoS Clin Trials (2006)

Bottom Line: Solicited and unsolicited adverse events and allele-specific antibody responses to recombinant MSP-1(42) and its subunits derived from P. falciparum strains homologous and heterologous to the 3D7 vaccine strain were measured.Immunization with the malaria vaccine was followed by significant increases in antibodies recognizing three diverse MSP-1(42) alleles and their subunits.Anti-MSP-1(42) antibody levels followed a seasonal pattern that was significantly augmented and prolonged by the malaria vaccine.

View Article: PubMed Central - PubMed

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

ABSTRACT

Objectives: The objectives were to evaluate the safety, reactogenicity, and allele-specific immunogenicity of the blood-stage malaria vaccine FMP1/AS02A in adults exposed to seasonal malaria and the impact of natural infection on vaccine-induced antibody levels.

Design: We conducted a randomized, double-blind, controlled phase I clinical trial.

Setting: Bandiagara, Mali, West Africa, is a rural town with intense seasonal transmission of Plasmodium falciparum malaria.

Participants: Forty healthy, malaria-experienced Malian adults aged 18-55 y were enrolled.

Interventions: The FMP1/AS02A malaria vaccine is a 42-kDa recombinant protein based on the carboxy-terminal end of merozoite surface protein-1 (MSP-1(42)) from the 3D7 clone of P. falciparum, adjuvanted with AS02A. The control vaccine was a killed rabies virus vaccine (Imovax). Participants were randomized to receive either FMP1/AS02A or rabies vaccine at 0, 1, and 2 mo and were followed for 1 y.

Outcome measures: Solicited and unsolicited adverse events and allele-specific antibody responses to recombinant MSP-1(42) and its subunits derived from P. falciparum strains homologous and heterologous to the 3D7 vaccine strain were measured.

Results: Transient local pain and swelling were more common in the malaria vaccine group than in the control group (11/20 versus 3/20 and 10/20 versus 6/20, respectively). MSP-1(42) antibody levels rose during the malaria transmission season in the control group, but were significantly higher in malaria vaccine recipients after the second immunization and remained higher after the third immunization relative both to baseline and to the control group. Immunization with the malaria vaccine was followed by significant increases in antibodies recognizing three diverse MSP-1(42) alleles and their subunits.

Conclusions: FMP1/AS02A was well tolerated and highly immunogenic in adults exposed to intense seasonal malaria transmission and elicited immune responses to genetically diverse parasite clones. Anti-MSP-1(42) antibody levels followed a seasonal pattern that was significantly augmented and prolonged by the malaria vaccine.

No MeSH data available.


Related in: MedlinePlus

Anti-MSP-142 Antibody TitersGeometric mean antibody titers to homologous recombinant MSP-142 for FMP1/AS02A vaccine (solid line) and control rabies vaccine (dotted line) recipients. Times of each of three immunizations and the start and end of the malaria transmission season are indicated by arrows. Bars represent 95% CI.
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pctr-0010034-g002: Anti-MSP-142 Antibody TitersGeometric mean antibody titers to homologous recombinant MSP-142 for FMP1/AS02A vaccine (solid line) and control rabies vaccine (dotted line) recipients. Times of each of three immunizations and the start and end of the malaria transmission season are indicated by arrows. Bars represent 95% CI.

Mentions: In the rabies vaccine group, anti-MSP-142 antibodies rose over the course of the malaria season, increasing more than 2-fold by day 60 and peaking at nearly 3-fold above baseline responses on day 180 as the malaria season ended (Figure 2; Table 3). Titers then decreased throughout the dry season and returned to near baseline levels by the start of the subsequent rainy season. In the FMP1/AS02A vaccine recipients, although the shape of the curve is similar, the magnitude of the response was significantly greater, with a 6.5-fold increase between day 0 and day 90, 30 d after the third immunization. At day 90, the geometric mean titers were 37,923 in the FMP1/AS02A recipients and 6,892 in the comparator group (p < 0.001), and at day 180, they were 29,150 and 9,089 (p = 0.016). By the final follow-up timepoint 1 y after immunization, although titers had waned in both groups, they remained significantly higher in the FMP1/AS02A group (14,693 compared to 5,015 in the control group; p = 0.032).


Safety and allele-specific immunogenicity of a malaria vaccine in Malian adults: results of a phase I randomized trial.

Thera MA, Doumbo OK, Coulibaly D, Diallo DA, Sagara I, Dicko A, Diemert DJ, Heppner DG, Stewart VA, Angov E, Soisson L, Leach A, Tucker K, Lyke KE, Plowe CV, Mali FMP1 Working Gro - PLoS Clin Trials (2006)

Anti-MSP-142 Antibody TitersGeometric mean antibody titers to homologous recombinant MSP-142 for FMP1/AS02A vaccine (solid line) and control rabies vaccine (dotted line) recipients. Times of each of three immunizations and the start and end of the malaria transmission season are indicated by arrows. Bars represent 95% CI.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC1851722&req=5

pctr-0010034-g002: Anti-MSP-142 Antibody TitersGeometric mean antibody titers to homologous recombinant MSP-142 for FMP1/AS02A vaccine (solid line) and control rabies vaccine (dotted line) recipients. Times of each of three immunizations and the start and end of the malaria transmission season are indicated by arrows. Bars represent 95% CI.
Mentions: In the rabies vaccine group, anti-MSP-142 antibodies rose over the course of the malaria season, increasing more than 2-fold by day 60 and peaking at nearly 3-fold above baseline responses on day 180 as the malaria season ended (Figure 2; Table 3). Titers then decreased throughout the dry season and returned to near baseline levels by the start of the subsequent rainy season. In the FMP1/AS02A vaccine recipients, although the shape of the curve is similar, the magnitude of the response was significantly greater, with a 6.5-fold increase between day 0 and day 90, 30 d after the third immunization. At day 90, the geometric mean titers were 37,923 in the FMP1/AS02A recipients and 6,892 in the comparator group (p < 0.001), and at day 180, they were 29,150 and 9,089 (p = 0.016). By the final follow-up timepoint 1 y after immunization, although titers had waned in both groups, they remained significantly higher in the FMP1/AS02A group (14,693 compared to 5,015 in the control group; p = 0.032).

Bottom Line: Solicited and unsolicited adverse events and allele-specific antibody responses to recombinant MSP-1(42) and its subunits derived from P. falciparum strains homologous and heterologous to the 3D7 vaccine strain were measured.Immunization with the malaria vaccine was followed by significant increases in antibodies recognizing three diverse MSP-1(42) alleles and their subunits.Anti-MSP-1(42) antibody levels followed a seasonal pattern that was significantly augmented and prolonged by the malaria vaccine.

View Article: PubMed Central - PubMed

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

ABSTRACT

Objectives: The objectives were to evaluate the safety, reactogenicity, and allele-specific immunogenicity of the blood-stage malaria vaccine FMP1/AS02A in adults exposed to seasonal malaria and the impact of natural infection on vaccine-induced antibody levels.

Design: We conducted a randomized, double-blind, controlled phase I clinical trial.

Setting: Bandiagara, Mali, West Africa, is a rural town with intense seasonal transmission of Plasmodium falciparum malaria.

Participants: Forty healthy, malaria-experienced Malian adults aged 18-55 y were enrolled.

Interventions: The FMP1/AS02A malaria vaccine is a 42-kDa recombinant protein based on the carboxy-terminal end of merozoite surface protein-1 (MSP-1(42)) from the 3D7 clone of P. falciparum, adjuvanted with AS02A. The control vaccine was a killed rabies virus vaccine (Imovax). Participants were randomized to receive either FMP1/AS02A or rabies vaccine at 0, 1, and 2 mo and were followed for 1 y.

Outcome measures: Solicited and unsolicited adverse events and allele-specific antibody responses to recombinant MSP-1(42) and its subunits derived from P. falciparum strains homologous and heterologous to the 3D7 vaccine strain were measured.

Results: Transient local pain and swelling were more common in the malaria vaccine group than in the control group (11/20 versus 3/20 and 10/20 versus 6/20, respectively). MSP-1(42) antibody levels rose during the malaria transmission season in the control group, but were significantly higher in malaria vaccine recipients after the second immunization and remained higher after the third immunization relative both to baseline and to the control group. Immunization with the malaria vaccine was followed by significant increases in antibodies recognizing three diverse MSP-1(42) alleles and their subunits.

Conclusions: FMP1/AS02A was well tolerated and highly immunogenic in adults exposed to intense seasonal malaria transmission and elicited immune responses to genetically diverse parasite clones. Anti-MSP-1(42) antibody levels followed a seasonal pattern that was significantly augmented and prolonged by the malaria vaccine.

No MeSH data available.


Related in: MedlinePlus