Induction of antigen-specific cytotoxic T lymphocytes in humans by a malaria DNA vaccine

Science

Volumn 282, Issue 5388, 1998, Pages 476-480

  Wang, Ruobing ^a,b   Doolan, Denise L ^a,c   Le, Thong P ^a,g   Hedstrom, Richard C ^a   Coonan, Kevin M ^d   Charoenvit, Yupin ^a   Jones, Trevor R ^a   Hobart, Peter ^e   Margalith, Michal ^e   Ng, Jennifer ^a   Weiss, Walter R ^a   Sedegah, Martha ^a   De Taisne, Charles ^f   Norman, Jon A ^e   Hoffman, Stephen L ^a  

^a NAVAL MEDICAL RESEARCH INSTITUTE   (United States)

^b HENRY M JACKSON FOUNDATION FOR THE ADVANCEMENT OF MILITARY MEDICINE   (United States)

^c PAN AMERICAN HEALTH ORGANIZATION   (United States)

^d UNITED STATES ARMY MEDICAL RESEARCH INSTITUTE OF INFECTIOUS DISEASES   (United States)

^e Vical   (United States)

^f Lab Pasteur Merieux Connaught   (France)

^g Pasteur Merieux Connaught USA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CD8 ANTIGEN; DNA VACCINE; HLA ANTIGEN CLASS 1; PLASMID DNA; PROTOZOAL PROTEIN;

ANTIGEN SPECIFICITY; CLINICAL TRIAL; CYTOTOXIC T LYMPHOCYTE; HUMAN; HUMAN CELL; HUMAN EXPERIMENT; INTRAMUSCULAR DRUG ADMINISTRATION; MAJOR HISTOCOMPATIBILITY COMPLEX RESTRICTION; MALARIA; MONONUCLEAR CELL; NORMAL HUMAN; PLASMODIUM FALCIPARUM; PRIORITY JOURNAL; REVIEW; VACCINATION;

ADULT; ANIMALS; ANTIGENS, PROTOZOAN; FEMALE; GENES, MHC CLASS I; HLA ANTIGENS; HUMANS; IMMUNIZATION SCHEDULE; MALARIA VACCINES; MALE; PLASMODIUM FALCIPARUM; PROTOZOAN PROTEINS; T-LYMPHOCYTES, CYTOTOXIC; VACCINATION; VACCINES, DNA;

ANIMALIA; PLASMODIUM FALCIPARUM;

EID: 0032538597     PISSN: 00368075     EISSN: None     Source Type: Journal    
DOI: 10.1126/science.282.5388.476     Document Type: Review

References (44)

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21. The study was a dose-escalating phase I safety and immunogenicity trial in healthy adult volunteers with informed consent. A total of 28 healthy, malaria-naïve volunteers were selected for the study on the basis of negative serologic studies for PfCSP, HIV, hepatitis B virus, hepatitis C virus, and smallpox. The volunteers were between 20 and 29 years old, and 61% were male. Complete class I and class II HLA typing profiles were obtained (21). Eight volunteers did not receive the PfCSP DNA vaccine and served as assay controls. Volunteer 33 (2500-μg-dosage group) was withdrawn from study after the second immunization because of an unplanned pregnancy.
22. T. P. Le et al., in preparation.
23. 51Cr [sodium chromate solution (Dupont New England Nuclear, Boston, MA)] for 90 min at 37°C and washed three times before use. The CTL activity was assessed by a conventional 6-hour chromium release assay, in the presence of a peptide (10 μg/ml). The percent lysis was defined as (experimental release - medium control release)/(maximum release - medium control release) × 100. The percent specific lysis was determined by subtracting the percent lysis of the targets that were sensitized with control peptide 242 from the percent lysis of the targets that were incubated with the experimental peptide. The results were expressed as the mean of triplicate determinations. The CTL responses were considered to be positive only if the percent specific lysis after immunization was ≥10% for at least two effector:target (E:T) ratios in the same assay and if the percent specific lysis before immunization was <10%. Spontaneous release values were always <20%.
24. 6 cells/ml in each vial, and the tubes were placed in a plastic foam container at -80°C overnight before being transferred to liquid nitrogen.
25. The CTL assays were conducted with four E:T combinations: (i) ALVAC PfCSP effectors and Western Reserve (WR) vaccinia PfCSP targets, (ii) ALVAC PfCSP effectors and experimental or control peptide-pulsed targets, (iii) experimental peptide-induced effectors and WR vaccinia PfCSP targets, and (iv) experimental peptide-induced effectors and experimental or control peptide-pulsed targets. All assays with WR vaccinia PfCSP-infected targets were excluded from the analysis because a simultaneous assay of PBMCs from control-naïve volunteers demonstrated an unacceptably high level of positivity (21). Assays that were conducted with PfCSP peptide-stimulated effectors against peptide-sensitized targets were not positive.
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42. Single-letter abbreviations for the amino acid residues are as follows: A, Ala; C, Cys; D, Asp; E, Glu; F, Phe; C, Gly; H, His; I, Ile; K, Lys; L, Leu; M, Met; N, Asn; P, Pro; Q, Gln; R, Arg; S, Ser; T, Thr; V, Val; W, Trp; and Y, Tyr.
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44. We are indebted to P. De la Vega, A. Figer, T. D. Bangura, S. Doria, V. Fallarame, and S. Abot for excellent technical assistance; W. O. Rogers for advice and support; J. Tine (Virogenetics), for providing the canary pox (ALVAC) and vaccinia (WR) viruses; A. Pedyczak (Pasteur-Merieux Connaught) for synthesis of PfCSP peptides; the many individuals at Vical who contributed to the project, especially S. Kradjian, R. Zaugg, and J. Meek; and Pasteur-Merieux Connaught for financial support. Our thanks extend to the volunteers, without whom this study would not have been possible. The research protocol for human participants in this study was approved by the Naval Medical Research Center's Committee for the Protection of Human Subjects, the U.S. Army Medical Research Institute of Infectious Diseases Human Use Committee, and the Surgeon General's Human Subjects Research Review Board, in accordance with the U.S. Navy regulation (SECNAVINST 3900.39B) governing the use of human participants in medical research. This work was supported in part by Naval Medical Research and Development Command Work Unit STO F 6.3a63002AA0101HFX, Office of Naval Research ATD PEN0603792 project R1889, and 060357OD.R357.6FDP9500-00.1532 Federal Defense Laboratories Diversification Program.