PMID- 17925866
OWN - NLM
STAT- MEDLINE
DCOM- 20080715
LR  - 20211020
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 2
IP  - 10
DP  - 2007 Oct 10
TI  - A randomized placebo-controlled phase Ia malaria vaccine trial of two 
      virosome-formulated synthetic peptides in healthy adult volunteers.
PG  - e1018
LID - e1018
AB  - BACKGROUND AND OBJECTIVES: Influenza virosomes represent an innovative 
      human-compatible antigen delivery system that has already proven its suitability 
      for subunit vaccine design. The aim of the study was to proof the concept that 
      virosomes can also be used to elicit high titers of antibodies against synthetic 
      peptides. The specific objective was to demonstrate the safety and immunogenicity 
      of two virosome-formulated P. falciparum protein derived synthetic peptide 
      antigens given in two different doses alone or in combination. 
      METHODOLOGY/PRINCIPAL FINDINGS: The design was a single blind, randomized, 
      placebo controlled, dose-escalating study involving 46 healthy Caucasian 
      volunteers aged 18-45 years. Five groups of 8 subjects received virosomal 
      formulations containing 10 microg or 50 microg of AMA 49-CPE, an apical membrane 
      antigen-1 (AMA-1) derived synthetic phospatidylethanolamine (PE)-peptide 
      conjugate or 10 ug or 50 ug of UK39, a circumsporozoite protein (CSP) derived 
      synthetic PE-peptide conjugate or 50 ug of both antigens each. A control group of 
      6 subjects received unmodified virosomes. Virosomal formulations of the antigens 
      (designated PEV301 and PEV302 for the AMA-1 and the CSP virosomal vaccine, 
      respectively) or unmodified virosomes were injected i. m. on days 0, 60 and 180. 
      In terms of safety, no serious or severe adverse events (AEs) related to the 
      vaccine were observed. 11/46 study participants reported 16 vaccine related local 
      AEs. Of these 16 events, all being pain, 4 occurred after the 1(st), 7 after the 
      2(nd) and 5 after the 3(rd) vaccination. 6 systemic AEs probably related to the 
      study vaccine were reported after the 1(st) injection, 10 after the 2(nd) and 6 
      after the 3(rd). Generally, no difference in the distribution of the systemic AEs 
      between either the doses applied (10 respectively 50 microg) or the synthetic 
      antigen vaccines (PEV301 and PEV302) used for immunization was found. In terms of 
      immunogenicity, both PEV301 and PEV302 elicited already after two injections a 
      synthetic peptide-specific antibody response in all volunteers immunized with the 
      appropriate dose. In the case of PEV301 the 50 microg antigen dose was associated 
      with a higher mean antibody titer and seroconversion rate than the 10 microg 
      dose. In contrast, for PEV302 mean titer and seroconversion rate were higher with 
      the lower dose. Combined delivery of PEV301 and PEV302 did not interfere with the 
      development of an antibody response to either of the two antigens. No relevant 
      antibody responses against the two malaria antigens were observed in the control 
      group receiving unmodified virosomes. CONCLUSIONS: The present study demonstrates 
      that three immunizations with the virosomal malaria vaccine components PEV301 
      or/and PEV302 (containing 10 microg or 50 microg of antigen) are safe and well 
      tolerated. At appropriate antigen doses seroconversion rates of 100% were 
      achieved. Two injections may be sufficient for eliciting an appropriate immune 
      response, at least in individuals with pre-existing anti-malarial immunity. These 
      results justify further development of a final multi-stage virosomal vaccine 
      formulation incorporating additional malaria antigens. TRIAL REGISTRATION: 
      ClinicalTrials.gov NCT00400101.
FAU - Genton, Blaise
AU  - Genton B
AD  - Swiss Tropical Institute, Basel, Switzerland. blaise.genton@unibas.ch
FAU - Pluschke, Gerd
AU  - Pluschke G
FAU - Degen, Lukas
AU  - Degen L
FAU - Kammer, Andreas R
AU  - Kammer AR
FAU - Westerfeld, Nicole
AU  - Westerfeld N
FAU - Okitsu, Shinji L
AU  - Okitsu SL
FAU - Schroller, Sandro
AU  - Schroller S
FAU - Vounatsou, Penelope
AU  - Vounatsou P
FAU - Mueller, Markus M
AU  - Mueller MM
FAU - Tanner, Marcel
AU  - Tanner M
FAU - Zurbriggen, Rinaldo
AU  - Zurbriggen R
LA  - eng
SI  - ClinicalTrials.gov/NCT00400101
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20071010
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Antigens, Viral)
RN  - 0 (Malaria Vaccines)
RN  - 0 (Peptides)
RN  - 0 (Phosphatidylethanolamines)
RN  - 0 (Placebos)
RN  - 0 (Virosomes)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Animals
MH  - Antigens, Viral/chemistry
MH  - Humans
MH  - Malaria/*prevention & control
MH  - Malaria Vaccines/*chemistry
MH  - Peptides/*chemistry
MH  - Phosphatidylethanolamines/chemistry
MH  - Placebos
MH  - Plasmodium falciparum/metabolism
MH  - Prospective Studies
MH  - Time Factors
MH  - Treatment Outcome
MH  - Virosomes/*chemistry
PMC - PMC2001290
COIS- Competing Interests: B. Genton received a travel grant from Berna Biotech to 
      attend an international meeting (unrelated to the present clinical trial). G. 
      Pluschke received research and travel grants from Pevion Biotech. A. Kammer, N. 
      Westerfeld and R. Zurbriggen are employees of Pevion Biotech.
EDAT- 2007/10/11 09:00
MHDA- 2008/07/17 09:00
PMCR- 2007/10/10
CRDT- 2007/10/11 09:00
PHST- 2007/07/18 00:00 [received]
PHST- 2007/09/25 00:00 [accepted]
PHST- 2007/10/11 09:00 [pubmed]
PHST- 2008/07/17 09:00 [medline]
PHST- 2007/10/11 09:00 [entrez]
PHST- 2007/10/10 00:00 [pmc-release]
AID - 07-PONE-CT-01791 [pii]
AID - 10.1371/journal.pone.0001018 [doi]
PST - epublish
SO  - PLoS One. 2007 Oct 10;2(10):e1018. doi: 10.1371/journal.pone.0001018.