TY - JOUR
T1 - Phase 1 trial of malaria transmission blocking vaccine candidates Pfs25 and Pvs 25 formulated with montanide ISA 51
AU - Wu, Yimin
AU - Ellis, Ruth D.
AU - Shaffer, Donna
AU - Fontes, Erica
AU - Malkin, Elissa M.
AU - Mahanty, Siddhartha
AU - Fay, Michael P.
AU - Narum, David
AU - Rausch, Kelly
AU - Miles, Aaron P.
AU - Aebig, Joan
AU - Orcutt, Andrew
AU - Muratova, Olga
AU - Song, Guanhong
AU - Lambert, Lynn
AU - Zhu, Daming
AU - Miura, Kazutoyo
AU - Long, Carole
AU - Saul, Allan
AU - Miller, Louis H.
AU - Durbin, Anna P.
PY - 2008/7/9
Y1 - 2008/7/9
N2 - Background: Pfs25 and Pvs25, surface proteins of mosquito stage of the malaria parasites P. falciparum and P. vivax, respectively, are leading candidates for vaccines preventing malaria transmission by mosquitoes. This single blinded, dose escalating, controlled Phase 1 study assessed the safety and immunogenicity of recombinant Pfs25 and Pvs25 formulated with Montanide ISA 51, a water-in-oil emulsion. Methodology/Principal Findings: The trial was conducted at The Johns Hopkins Center for Immunization Research, Washington DC, USA, between May 16, 2005-April 30, 2007. The trial was designed to enroll 72 healthy male and non-pregnant female volunteers into 1 group to receive adjuvant control and 6 groups to receive escalating doses of the vaccines. Due to unexpected reactogenicity, the vaccination was halted and only 36 volunteers were enrolled into 4 groups: 3 groups of 10 volunteers each were immunized with 5 μg of Pfs25/ISA 51, 5 μg of Pvs25/ISA 51, or 20 μg of Pvs25/ISA 51, respectively. A fourth group of 6 volunteers received adjuvant control (PBS/ISA 51). Frequent local reactogenicity was observed. Systemic adverse events included two cases of erythema nodosum considered to be probably related to the combination of the antigen and the adjuvant. Significant antibody responses were detected in volunteers who completed the lowest scheduled doses of Pfs25/ISA 51. Serum anti-Pfs25 levels correlated with transmission blocking activity. Conclusion/Significance: It is feasible to induce transmission blocking immunity in humans using the Pfs25/ISA 51 vaccine, but these vaccines are unexpectedly reactogenic for further development. This is the first report that the formulation is associated with systemic adverse events including erythema nodosum.
AB - Background: Pfs25 and Pvs25, surface proteins of mosquito stage of the malaria parasites P. falciparum and P. vivax, respectively, are leading candidates for vaccines preventing malaria transmission by mosquitoes. This single blinded, dose escalating, controlled Phase 1 study assessed the safety and immunogenicity of recombinant Pfs25 and Pvs25 formulated with Montanide ISA 51, a water-in-oil emulsion. Methodology/Principal Findings: The trial was conducted at The Johns Hopkins Center for Immunization Research, Washington DC, USA, between May 16, 2005-April 30, 2007. The trial was designed to enroll 72 healthy male and non-pregnant female volunteers into 1 group to receive adjuvant control and 6 groups to receive escalating doses of the vaccines. Due to unexpected reactogenicity, the vaccination was halted and only 36 volunteers were enrolled into 4 groups: 3 groups of 10 volunteers each were immunized with 5 μg of Pfs25/ISA 51, 5 μg of Pvs25/ISA 51, or 20 μg of Pvs25/ISA 51, respectively. A fourth group of 6 volunteers received adjuvant control (PBS/ISA 51). Frequent local reactogenicity was observed. Systemic adverse events included two cases of erythema nodosum considered to be probably related to the combination of the antigen and the adjuvant. Significant antibody responses were detected in volunteers who completed the lowest scheduled doses of Pfs25/ISA 51. Serum anti-Pfs25 levels correlated with transmission blocking activity. Conclusion/Significance: It is feasible to induce transmission blocking immunity in humans using the Pfs25/ISA 51 vaccine, but these vaccines are unexpectedly reactogenic for further development. This is the first report that the formulation is associated with systemic adverse events including erythema nodosum.
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U2 - 10.1371/journal.pone.0002636
DO - 10.1371/journal.pone.0002636
M3 - Article
C2 - 18612426
AN - SCOPUS:49949097129
SN - 1932-6203
VL - 3
JO - PloS one
JF - PloS one
IS - 7
M1 - e2636
ER -