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Safety and reactogenicity of an MSP-1 malaria vaccine candidate: a randomized phase Ib dose-escalation trial in Kenyan children.

Withers MR, McKinney D, Ogutu BR, Waitumbi JN, Milman JB, Apollo OJ, Allen OG, Tucker K, Soisson LA, Diggs C, Leach A, Wittes J, Dubovsky F, Stewart VA, Remich SA, Cohen J, Ballou WR, Holland CA, Lyon JA, Angov E, Stoute JA, Martin SK, Heppner DG, MSP-1 Malaria Vaccine Working Gro - PLoS Clin Trials (2006)

Bottom Line: Both vaccines were safe and well tolerated.FMP1/AS02A recipients experienced significantly more pain and injection-site swelling with a dose-effect relationship.The FMP1/AS02A vaccine was safe and immunogenic in malaria-exposed 12- to 47-mo-old children and the magnitude of immune response of the 25 and 50 microg doses was superior to that of the 10 microg dose.

View Article: PubMed Central - PubMed

Affiliation: United States Army Medical Research Unit-Kenya, Nairobi, Kenya. mwithers@us.army.mil

ABSTRACT

Objective: Our aim was to evaluate the safety, reactogenicity, and immunogenicity of an investigational malaria vaccine.

Design: This was an age-stratified phase Ib, double-blind, randomized, controlled, dose-escalation trial. Children were recruited into one of three cohorts (dosage groups) and randomized in 2:1 fashion to receive either the test product or a comparator.

Setting: The study was conducted in a rural population in Kombewa Division, western Kenya.

Participants: Subjects were 135 children, aged 12-47 mo.

Interventions: Subjects received 10, 25, or 50 microg of falciparum malaria protein 1 (FMP1) formulated in 100, 250, and 500 microL, respectively, of AS02A, or they received a comparator (Imovax (rabies vaccine).

Outcome measures: We performed safety and reactogenicity parameters and assessment of adverse events during solicited (7 d) and unsolicited (30 d) periods after each vaccination. Serious adverse events were monitored for 6 mo after the last vaccination.

Results: Both vaccines were safe and well tolerated. FMP1/AS02A recipients experienced significantly more pain and injection-site swelling with a dose-effect relationship. Systemic reactogenicity was low at all dose levels. Hemoglobin levels remained stable and similar across arms. Baseline geometric mean titers were comparable in all groups. Anti-FMP1 antibody titers increased in a dose-dependent manner in subjects receiving FMP1/AS02A; no increase in anti-FMP1 titers occurred in subjects who received the comparator. By study end, subjects who received either 25 or 50 microg of FMP1 had similar antibody levels, which remained significantly higher than that of those who received the comparator or 10 microg of FMP1. A longitudinal mixed effects model showed a statistically significant effect of dosage level on immune response (F(3,1047) = 10.78, or F(3, 995) = 11.22, p < 0.001); however, the comparison of 25 microg and 50 microg recipients indicated no significant difference (F(1,1047) = 0.05; p = 0.82).

Conclusions: The FMP1/AS02A vaccine was safe and immunogenic in malaria-exposed 12- to 47-mo-old children and the magnitude of immune response of the 25 and 50 microg doses was superior to that of the 10 microg dose.

No MeSH data available.


Related in: MedlinePlus

Reverse Cumulative Plot of Anti-FMP1 Titer Ratios, by Dose Cohort, for Subjects Receiving All Three Vaccinations(A) Ratios are depicted comparing study day 0 titers to study day 74.(B) Ratios are depicted comparing study day 0 titers to study day 364.
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pctr-0010032-g003: Reverse Cumulative Plot of Anti-FMP1 Titer Ratios, by Dose Cohort, for Subjects Receiving All Three Vaccinations(A) Ratios are depicted comparing study day 0 titers to study day 74.(B) Ratios are depicted comparing study day 0 titers to study day 364.

Mentions: Titer ratio plots indicate the percentage of subjects experiencing specific fold rises in antibody response over baseline values (Figure 3). At study day 74, the graph indicates that approximately 50% of subjects receiving the 10-μg dose of FMP1/AS02A experienced at least a 4-fold rise, and approximately 50% of subjects receiving the 25- or 50-μg dose experienced at least a 16-fold rise. At study day 364, approximately 50% of subjects in the 25- and 50-μg dose cohorts of the FMP1/AS02A group showed at least a 4-fold rise in antibody titer, and at least 20% of these two cohorts maintained a 16-fold rise.


Safety and reactogenicity of an MSP-1 malaria vaccine candidate: a randomized phase Ib dose-escalation trial in Kenyan children.

Withers MR, McKinney D, Ogutu BR, Waitumbi JN, Milman JB, Apollo OJ, Allen OG, Tucker K, Soisson LA, Diggs C, Leach A, Wittes J, Dubovsky F, Stewart VA, Remich SA, Cohen J, Ballou WR, Holland CA, Lyon JA, Angov E, Stoute JA, Martin SK, Heppner DG, MSP-1 Malaria Vaccine Working Gro - PLoS Clin Trials (2006)

Reverse Cumulative Plot of Anti-FMP1 Titer Ratios, by Dose Cohort, for Subjects Receiving All Three Vaccinations(A) Ratios are depicted comparing study day 0 titers to study day 74.(B) Ratios are depicted comparing study day 0 titers to study day 364.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC1851726&req=5

pctr-0010032-g003: Reverse Cumulative Plot of Anti-FMP1 Titer Ratios, by Dose Cohort, for Subjects Receiving All Three Vaccinations(A) Ratios are depicted comparing study day 0 titers to study day 74.(B) Ratios are depicted comparing study day 0 titers to study day 364.
Mentions: Titer ratio plots indicate the percentage of subjects experiencing specific fold rises in antibody response over baseline values (Figure 3). At study day 74, the graph indicates that approximately 50% of subjects receiving the 10-μg dose of FMP1/AS02A experienced at least a 4-fold rise, and approximately 50% of subjects receiving the 25- or 50-μg dose experienced at least a 16-fold rise. At study day 364, approximately 50% of subjects in the 25- and 50-μg dose cohorts of the FMP1/AS02A group showed at least a 4-fold rise in antibody titer, and at least 20% of these two cohorts maintained a 16-fold rise.

Bottom Line: Both vaccines were safe and well tolerated.FMP1/AS02A recipients experienced significantly more pain and injection-site swelling with a dose-effect relationship.The FMP1/AS02A vaccine was safe and immunogenic in malaria-exposed 12- to 47-mo-old children and the magnitude of immune response of the 25 and 50 microg doses was superior to that of the 10 microg dose.

View Article: PubMed Central - PubMed

Affiliation: United States Army Medical Research Unit-Kenya, Nairobi, Kenya. mwithers@us.army.mil

ABSTRACT

Objective: Our aim was to evaluate the safety, reactogenicity, and immunogenicity of an investigational malaria vaccine.

Design: This was an age-stratified phase Ib, double-blind, randomized, controlled, dose-escalation trial. Children were recruited into one of three cohorts (dosage groups) and randomized in 2:1 fashion to receive either the test product or a comparator.

Setting: The study was conducted in a rural population in Kombewa Division, western Kenya.

Participants: Subjects were 135 children, aged 12-47 mo.

Interventions: Subjects received 10, 25, or 50 microg of falciparum malaria protein 1 (FMP1) formulated in 100, 250, and 500 microL, respectively, of AS02A, or they received a comparator (Imovax (rabies vaccine).

Outcome measures: We performed safety and reactogenicity parameters and assessment of adverse events during solicited (7 d) and unsolicited (30 d) periods after each vaccination. Serious adverse events were monitored for 6 mo after the last vaccination.

Results: Both vaccines were safe and well tolerated. FMP1/AS02A recipients experienced significantly more pain and injection-site swelling with a dose-effect relationship. Systemic reactogenicity was low at all dose levels. Hemoglobin levels remained stable and similar across arms. Baseline geometric mean titers were comparable in all groups. Anti-FMP1 antibody titers increased in a dose-dependent manner in subjects receiving FMP1/AS02A; no increase in anti-FMP1 titers occurred in subjects who received the comparator. By study end, subjects who received either 25 or 50 microg of FMP1 had similar antibody levels, which remained significantly higher than that of those who received the comparator or 10 microg of FMP1. A longitudinal mixed effects model showed a statistically significant effect of dosage level on immune response (F(3,1047) = 10.78, or F(3, 995) = 11.22, p < 0.001); however, the comparison of 25 microg and 50 microg recipients indicated no significant difference (F(1,1047) = 0.05; p = 0.82).

Conclusions: The FMP1/AS02A vaccine was safe and immunogenic in malaria-exposed 12- to 47-mo-old children and the magnitude of immune response of the 25 and 50 microg doses was superior to that of the 10 microg dose.

No MeSH data available.


Related in: MedlinePlus