Phase 1 trial of malaria transmission blocking vaccine candidates Pfs25 and Pvs 25 formulated with montanide ISA 51

Yimin Wu, Ruth D. Ellis, Donna Shaffer, Erica Fontes, Elissa M. Malkin, Siddhartha Mahanty, Michael P. Fay, David Narum, Kelly Rausch, Aaron P. Miles, Joan Aebig, Andrew Orcutt, Olga Muratova, Guanhong Song, Lynn Lambert, Daming Zhu, Kazutoyo Miura, Carole Long, Allan Saul, Louis H. Miller & 1 others Anna P Durbin

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Article numbere2636
JournalPLoS One
Volume3
Issue number7
DOIs
StatePublished - Jul 9 2008

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malaria
Malaria
volunteers
Volunteers
Vaccines
vaccines
adjuvants
Erythema Nodosum
erythema
Culicidae
Immunization
dosage
Malaria Vaccines
Emulsions
District of Columbia
surface proteins
Oils
Membrane Proteins
Antibody Formation
emulsions

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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Phase 1 trial of malaria transmission blocking vaccine candidates Pfs25 and Pvs 25 formulated with montanide ISA 51. / Wu, Yimin; Ellis, Ruth D.; Shaffer, Donna; Fontes, Erica; Malkin, Elissa M.; Mahanty, Siddhartha; Fay, Michael P.; Narum, David; Rausch, Kelly; Miles, Aaron P.; Aebig, Joan; Orcutt, Andrew; Muratova, Olga; Song, Guanhong; Lambert, Lynn; Zhu, Daming; Miura, Kazutoyo; Long, Carole; Saul, Allan; Miller, Louis H.; Durbin, Anna P.

In: PLoS One, Vol. 3, No. 7, e2636, 09.07.2008.

Research output: Contribution to journalArticle

Wu, Y, Ellis, RD, Shaffer, D, Fontes, E, Malkin, EM, Mahanty, S, Fay, MP, Narum, D, Rausch, K, Miles, AP, Aebig, J, Orcutt, A, Muratova, O, Song, G, Lambert, L, Zhu, D, Miura, K, Long, C, Saul, A, Miller, LH & Durbin, AP 2008, 'Phase 1 trial of malaria transmission blocking vaccine candidates Pfs25 and Pvs 25 formulated with montanide ISA 51', PLoS One, vol. 3, no. 7, e2636. https://doi.org/10.1371/journal.pone.0002636
Wu, Yimin ; Ellis, Ruth D. ; Shaffer, Donna ; Fontes, Erica ; Malkin, Elissa M. ; Mahanty, Siddhartha ; Fay, Michael P. ; Narum, David ; Rausch, Kelly ; Miles, Aaron P. ; Aebig, Joan ; Orcutt, Andrew ; Muratova, Olga ; Song, Guanhong ; Lambert, Lynn ; Zhu, Daming ; Miura, Kazutoyo ; Long, Carole ; Saul, Allan ; Miller, Louis H. ; Durbin, Anna P. / Phase 1 trial of malaria transmission blocking vaccine candidates Pfs25 and Pvs 25 formulated with montanide ISA 51. In: PLoS One. 2008 ; Vol. 3, No. 7.
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abstract = "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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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

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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.

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