The Impact of “Omic” and Imaging Technologies on Assessing the Host Immune Response to Biodefence Agents

Table 1

Microarray studies performed with various Biodefence Agents.

Pathogen	Purpose of study	Arrays used	Material tested	Reference
Response to infection
Burkholderia pseudomallei	Profile human antibody responses in healthy and recovered patients.	Protein array containing 154 B.  pseudomallei proteins.	Human plasma from healthy and recovered melioidosis patients.	[33]
Burkholderia pseudomallei	Gene expression changes following intravenous infection with bacteria in BALB/c mice.	Sentrix MouseRef-8 cDNA array (Illumina).	Liver and spleen from BALB/c mice.	[24]
Burkholderia pseudomallei	Differences in gene expression after 2 hour exposure to B.  pseudomallei and B.  thailandensis in vitro.	GeneChip human genome U133 (Affymetrix).	A549 human lung epithelial cells.	[22]
Bacillus anthracis	Gene expression changes in cells exposed to Edema toxin.	GeneChip murine genome (Affymetrix).	RAW 264.7 murine macrophages.	[17]
Bacillus anthracis	Gene expression changes in cells exposed to lethal toxin.	GeneChip human genome U133 plus 2.0 (Affymetrix).	Human monocytes from the blood of naïve volunteers.	[8]
Bacillus anthracis	Murine macrophage gene expression changes following exposure to protective antigen and lethal factor from B.  anthracis.	PCR product DNA array.	RAW 264.7 murine macrophages.	[18]
Bacillus anthracis spores	Gene expression profiling of human macrophages following infection in vitro.	GeneChip human genome U133 Plus 2.0 (Affymetrix).	Human alveolar macrophages following bronchoscopy.	[9]
Brucella melitensis	Gene expression analysis of mucosal epithelial cells following infection in vitro.	10K human ESTs microarray (Microarray centre, Ontario, Canada).	Epithelial-like human HeLa cell line.	[19]
Brucella melitensis	Kinetics of human antibody responses to acute and chronic brucellosis.	Brucella melitensis protein array.	Sera from brucellosis patients.	[34]
Brucella melitensis	Investigate host gene changes in vivo following infection with Brucella in a calf ligated ileal loop model.	Custom-made 13K bovine 70 mer oligo array.	Infected Peyer’s patch from calf ligated ileal loop.	[31]
Brucella melitensis	Full proteome-wide serological analysis of B.  melitensis in humans.	Protein microarray containing 3046 proteins from B.  melitensis.	Sera from brucellosis patients.	[35]
Coxiella burnetii	Profile humoral immune response of naïve and acute Q-fever patients.	Protein microarray containing 84% of C.  burnetii.	Human sera from Q-fever patients.	[36]
Coxiella burnetii	Comparison of the antibody profiles from acute and chronic Q-fever patients.	Protein microarray containing 93% of C.  burnetii.	Human sera from Q-fever patients.	[37]
Coxiella burnetii	Define the humoral immune profile using Q-fever patient sera.	Custom-made protein microarray containing 19 proteins from C.  burnetii.	Human sera from Q-fever patients.	[38]
Ebola and Marburg viruses	Gene signatures following infection in vitro with Ebola virus, Marburg virus.	Human cDNA array (Agilent).	Human hepatoblastoma (Huh7) cells.	[20]
Ebola virus	Entry into human macrophages. Infection studies in vitro.	GeneChip human genome HG-U95Av2 array (Affymetrix).	Primary human macrophages.	[10]
Francisella tularensis live vaccine strain (LVS)	Human neutrophil gene expression, in vitro infection studies.	GeneChip human genome U133 plus 2.0 (Affymetrix).	Polymorphonuclear leukocytes (PMNs) from human blood.	[11]
Francisella tularensis  LVS	In vitro infection studies using Human PBMCs.	Human gene array (Affymetrix).	Human peripheral blood mononuclear cells (PBMCs).	[12]
Francisella tularensis (SchuS4)	Gene expression following inhalation of F.  tularensis in BALB/c mice.	Mouse array covering 1500 genes. (Ocimumbio).	Lung tissue taken from infected BALB/c mice.	[27]
Francisella tularensis (FSC033/snMF)	Gene expression following aerosol exposure with F.  tularensis in C57BL/6 mice.	Custom-made mouse cDNA array.	Lung tissue taken from infected C57BL/6 mice.	[30]
Francisella tularensis (SchuS4)	Gene expression of human monocytes infected in vitro with F.  tularensis.	GeneChip human genome U133 plus 2 (Affymetrix).	Naïve human peripheral blood monocytes.	[13]
Francisella tularensis (SchuS4)	Comparison of mouse global transcriptional responses to F. tularensis, Yersinia pestis, Pseudomonas aeruginosa and  Legionella pneumophila.	Mouse whole genome 44K arrays (Agilent).	Lung tissue from infected BALB/c mice.	[29]
Monkeypox and Vaccinia virus	Comparison of gene expression profiles following infection in vitro with Monkeypox or Vaccinia virus.	Human cDNA arrays with 406 Variola and Vaccinia virus genes.	Primary human macrophages, primary human fibroblasts and HeLa cells.	[14]
Monkeypox and Vaccinia virus	Comparison of gene expression profiles, in vitro infection studies.	Whole human genome oligo microarray (Agilent).	HeLa cells.	[16]
Monkeypox virus	Gene expression changes in vitro 3 and 7 hours post-challenge with Monkeypox virus.	Rhesus macaque genome microarrays (Affymetrix).	Macaca mulatta kidney cells (MK2).	[21]
Monkeypox virus	Comparison of antibody responses to monkeypox virus infection and human smallpox vaccination.	Protein array covering 92–95% of representative proteins from Monkeypox and Vaccinia virus.	Blood from humans with smallpox vaccination and cyno macaques infected with Monkeypox virus.	[39]
Variola virus	Host gene expression changes in Variola virus infected cynomolgus macaques.	Human cDNA microarrays.	PBMC’s sampled from infected monkeys.	[5]
Yersinia pestis	Gene expression changes following infection in vitro.	Human nylon blots (1185 cDNA spots) (Clontech).	Primary human monocytes and/or mixed with lymphocytes (PBMCs).	[15]
Venezuelan equine encephalitis virus (VEEV)	Gene expression of VEEV infected mice.	Oligo array mouse 70 mer. (Operon) & GEArray, focused mouse Toll-like receptor signaling microarray.	VEEV infected mouse brain CD-1 mice.	[25, 26]
Vaccines
Anthrax vaccine adjuvant CpG ODN	Measure gene expression changes in mice and splenocytes treated with CpG ODN.	Murine oligonucleotide array (custom-made).	Spleens and splenocytes from various breds of mice.	[40–42]
Francisella tularensis LVS	Assess the memory response of PBMCs taken from LVS vaccinated and naïve humans.	GeneChip human genome U133 (Affymetrix).	Re-stimulated PBMCs from LVS vaccinated and naïve humans.	[43]
Killed Francisella tularensis (LVS) adjuvanted with ISCOMS admixed with CpG	Define antibody profiles of vaccinated mice.	Whole proteome microarray custom-made.	BALB/c mice vaccinated with LVS.	[44]
Q-fever vaccine	Assess antibody immune profiles of Q-Vax vaccinated humans.	C.  burnetii protein microarray (custom-made).	Sera from vaccinated humans.	[45]
Smallpox vaccines	Assess antibody profiles generated to MVA, Acam2000 and/or Dryvax smallpox vaccines.	Protein array containing Vaccinia virus proteins [46].	Mouse, rabbit, macaque, black-tailed prairie dog and human sera.	[47–51]
Therapies
Anti-coagulant treatments for Ebola virus infection	Comparison of NHP host genome responses responding to candidate therapeutics following infection with Ebola virus.	Human genome cDNA microarray.	PBMC’s from rhesus macaques infected with ZEBOV and treated shortly after exposure with rNAPc2 or rhAPC.	[32]

Omission from this table does not constitute absence of data.