Safety and reactogenicity of an MSP-1 malaria vaccine candidate: a randomized phase Ib dose-escalation trial in Kenyan children.
OBJECTIVE
Our aim was to evaluate the safety, reactogenicity, and immunogenicity of an investigational malaria vaccine.


METHODS
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.


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


METHODS
Subjects were 135 children, aged 12-47 mo.


METHODS
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).


METHODS
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.
Withers
Mark R
MR
United States Army Medical Research Unit-Kenya, Nairobi, Kenya. mwithers@us.army.mil
McKinney
Denise
D
Ogutu
Bernhards R
BR
Waitumbi
John N
JN
Milman
Jessica B
JB
Apollo
Odika J
OJ
Allen
Otieno G
OG
Tucker
Kathryn
K
Soisson
Lorraine A
LA
Diggs
Carter
C
Leach
Amanda
A
Wittes
Janet
J
Dubovsky
Filip
F
Stewart
V Ann
VA
Remich
Shon A
SA
Cohen
Joe
J
Ballou
W Ripley
WR
Holland
Carolyn A
CA
Lyon
Jeffrey A
JA
Angov
Evelina
E
Stoute
José A
JA
Martin
Samuel K
SK
Heppner
D Gray
DG