Linked Life Data

1563771

Source:http://linkedlifedata.com/resource/pubmed/id/1563771

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1992-5-19
pubmed:abstractText
Twenty-one malaria-naive volunteers were immunized with a vaccine consisting of a 22-kDa recombinant peptide (R32LR), derived from the repeat region of Plasmodium falciparum circumsporozoite (CS) protein, covalently coupled to detoxified Pseudomonas aeruginosa toxin A. Nineteen volunteers received a second dose of vaccine at 8 weeks, and eighteen received a third dose at 8 to 12 months. The vaccine was well tolerated, with only one volunteer developing local discomfort and induration at the site of injection which limited function for 48 h. The geometric mean anti-CS immunoglobulin G antibody concentration 2 weeks after the second dose of vaccine was 10.6 micrograms/ml (standard deviation = 3.0 micrograms/ml). Eleven volunteers (52%) developed anti-CS antibody levels of greater than 9.8 micrograms/ml, the level measured in the one volunteer protected against P. falciparum challenge after immunization with the alum-adjuvanted recombinant protein R32tet32 in a prior study. Three separate experimental challenges were conducted with 10 volunteers 2 to 4 weeks after the third dose of vaccine. The four best responders, on the basis of antibody levels (6 to 26 micrograms/ml), were challenged with two infected-mosquito bites, but only one of four immunized volunteers and one of three malaria-naive controls became parasitemic. In a second challenge study using five infected-mosquito bites as the challenge dose, three of three malaria-naive control volunteers and two of three immunized volunteers developed malaria. The third vaccine was apparently completely protected. In the third and last challenge, three of three controls and five of five vaccinees became infected. Sera obtained on the days of challenge inhibited sporozoite invasion of hepatocytes variably in vitro (range, 45 to 90% inhibition), but the degree of inhibition did not correlate with protection. Although antibody against the CS repeat region may protect some individuals against experimental challenge, this protection cannot be predicted from antibody levels by current in vitro assays. The functionality and fine specificity of anti-CS antibody are probably critical determinants.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/1563771-1695491, http://linkedlifedata.com/resource/pubmed/commentcorrection/1563771-1729706, http://linkedlifedata.com/resource/pubmed/commentcorrection/1563771-2175464, http://linkedlifedata.com/resource/pubmed/commentcorrection/1563771-2240371, http://linkedlifedata.com/resource/pubmed/commentcorrection/1563771-2439920, http://linkedlifedata.com/resource/pubmed/commentcorrection/1563771-2884410, http://linkedlifedata.com/resource/pubmed/commentcorrection/1563771-2988126, http://linkedlifedata.com/resource/pubmed/commentcorrection/1563771-3047062, http://linkedlifedata.com/resource/pubmed/commentcorrection/1563771-4987037, http://linkedlifedata.com/resource/pubmed/commentcorrection/1563771-6189951, http://linkedlifedata.com/resource/pubmed/commentcorrection/1563771-6380022, http://linkedlifedata.com/resource/pubmed/commentcorrection/1563771-6404817
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0019-9567
pubmed:author
pubmed:issnType
Print
pubmed:volume
60
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1834-9
pubmed:dateRevised
2010-9-7
pubmed:meshHeading
pubmed:year
1992
pubmed:articleTitle
Safety, immunogenicity, and efficacy of a Plasmodium falciparum vaccine comprising a circumsporozoite protein repeat region peptide conjugated to Pseudomonas aeruginosa toxin A.
pubmed:affiliation
Center for Immunization Research, Johns Hopkins University School of Hygiene and Public Health, Baltimore, Maryland 21205.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S.