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Biomedical subjects

David Burt

Publications and source records attributed to David Burt.

4 recordsLinked to original sources

Safety and immunogenicity of a Proteosome -trivalent inactivated influenza vaccine, given nasally to healthy adults.

We studied the safety and immunogenicity of a nasally administered vaccine comprising three monovalent inactivated influenza antigens (A/New Caledonia/20/99 (H1N1), A/Panama/2007/99 (H3N2), and B/Guangdong/120/2000) non-covalently associated with outer membrane proteins of Neisseria meningitidis (Proteosome) in normal, healthy adults. In a randomized, double-blind trial participants (n = 78) were allocated to placebo or a single nasal dose of vaccine containing 15, 30, or 45 microg of each of the three HA antigens, or two nasal doses containing 30 microg of each HA, separated by 2 weeks. The vaccine was generally well tolerated in all doses tested, and in a one or two-dose schedule. A shallow vaccine reactogenicity dose-response was seen. The most common local reaction was nasal congestion, which occurred in up to 48.3% of vaccine recipients in days 0-6 after vaccine but was mild and self-limiting; this reaction was not significantly more common among active vaccine recipients than placebo recipients. Mild to moderate headache was the most commonly reported systemic reactogenicity complaint in all treatment groups, and was the only solicited complaint to increase significantly in frequency after a second active dose. No severe systemic reactions occurred. A positive and statistically significant antibody response was observed, in serum and in nasal secretions, to increasing dose for all three antigens. Serum HAI titre responses and nasal secretory IgA immune responses were elicited against all three antigens. Further testing of this nasal influenza vaccine is warranted to determine its safety and immunogenicity in these populations and its efficacy in the prevention of clinical illness.

Administration, Intranasal↗

Intranasal administration of a proteosome-influenza vaccine is well-tolerated and induces serum and nasal secretion influenza antibodies in healthy human subjects.

Two randomized, blinded, active comparator-controlled trials of a prototype monovalent A/Beijing/262/95 (H1N1) - proteosome vaccine delivered by intranasal spray were performed in healthy adults. Overall, the intranasal proteosome-adjuvanted vaccine was well-tolerated with only mild stuffy nose and rhinorrhea seen more frequently in recipients of vaccine than in recipients of intranasal saline, and there were no serious adverse events. The intranasal proteosome-adjuvanted vaccine induced serum hemagglutination inhibiting (HAI) and nasal secretory IgA (sIgA) responses specific for the influenza antigen. Serum HAI responses were most influenced by the dosage level, whereas mucosal sIgA responses, although demonstrable with both single-dose and two-dose vaccine regimens, appeared to be greater in response to two-dose regimens (regardless of dose level). Further evaluation of mucosal influenza immunization using the proteosome adjuvant/delivery system is clearly warranted.

Adjuvants, Immunologic↗

Development of a cDNA array for chicken gene expression analysis.

BACKGROUND: The application of microarray technology to functional genomic analysis in the chicken has been limited by the lack of arrays containing large numbers of genes. RESULTS: We have produced cDNA arrays using chicken EST collections generated by BBSRC, University of Delaware and the Fred Hutchinson Cancer Research Center. From a total of 363,838 chicken ESTs representing 24 different adult or embryonic tissues, a set of 11,447 non-redundant ESTs were selected and added to an existing collection of clones (4,162) from immune tissues and a chicken bursal cell line (DT40). Quality control analysis indicates there are 13,007 useable features on the array, including 160 control spots. The array provides broad coverage of mRNAs expressed in many tissues; in addition, clones with expression unique to various tissues can be detected. CONCLUSIONS: A chicken multi-tissue cDNA microarray with 13,007 features is now available to academic researchers from http://genomics@fhcrc.org. Sequence information for all features on the array is in GenBank, and clones can be readily obtained. Targeted users include researchers in comparative and developmental biology, immunology, vaccine and agricultural technology. These arrays will be an important resource for the entire research community using the chicken as a model.

Animals↗

A novel approach to assess inter-rater reliability in the use of the Overt Aggression Scale-Modified.

The ability of raters to apply measures of efficacy accurately and reproducibly in clinical trials of psychotropic medications is vital to the validity of study data. In a large, multi-center trial using the Overt Aggression Scale-Modified (OAS-M), inter-rater reliability was evaluated using standardized patients (SP) in a live 'mock' interview. Thirty raters experienced in the OAS-M each interviewed two actors trained to portray patients with intermittent explosive disorder, borderline and antisocial personality disorder, and/or post-traumatic stress disorder. Inter-rater reliability of OAS-M scores was evaluated using the intra-class correlation coefficient (ICC). The joint reliability of the raters in the study with an expert rater was also assessed by an ICC. The ICC was 0.96 between the raters, and 0.98 between the raters and expert rater. Results suggest that SP can be utilized in rater assessment and that raters administering the OAS-M in this model of rater reliability assessment demonstrate a high level of consistency and reliability. The method described here may be useful in future assessments of inter-rater reliability.

Adult↗