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Clinical

- Study Type: Vaccine

Purpose

LAIV and TIV are effective for prevention of influenza infection in children, but the mechanisms associated with protection are still not well defined. We analyzed the differences in B cell responses and transcriptional profiles. Compared to baseline, LAIV elicited a significant increase in naïve, memory and transitional B cells on day 30, while vaccination with TIV elicited an increase in number of plasmablasts on day 7. Antibody titers against the three vaccine strains (H1N1, H3N2 and B) were significantly higher in the TIV group and correlated with number of antibody-secreting cells. Regarding transcriptional profiles, both vaccines induced expression of interferon signaling, but at different time points, TIV on 1 day, and LAIV on day 7 day post-vaccination, the last only in children younger than 5 years old. Interferon-related genes over expressed in both vaccinated groups correlated with antibody titers of H3N2 vaccines strain. These results suggest that LAIV and TIV induced significant different B cell responses in vaccinated children. Early induction on interferon genes appears important for development of effective antibody responses.

Hypothesis

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Experimental Design

Longitudinal study with time points at baseline (day 0), 24hr, day 7 and day 30. 136 total samples analyzed. This was a prospective cohort of previously healthy children 6 months to 14 years of age enrolled between October 2011 and February 2012. Thirty seven subjects were randomized to receive one dose of either LAIV (FluMist®, MedImmune) (n= 20) or TIV (Fluzone®, Sanofi Pasteur) (n= 17). Two exceptions were applied to the randomization: four children with ages between 6 months and 2 years old received TIV, since LAIV is not licensed on this age group, and four children with controlled asthma also received TIV following CDC’s recommendations. One child aged 6 months at the time of enrollment received two doses of the vaccine with one month interval apart, since it was his first influenza vaccination. Exclusion criteria included any medical comorbidities or chronic conditions (lung, kidney or heart disease), use of systemic steroids in the previous 2 weeks, and congenital or acquired immunodeficiencies. The 2011-2012 LAIV and TIV vaccines contained A/California/7/2009 (H1N1)-like, A/Perth/16/2009 (H3N2)-like and B/Brisbane/60/2008-like antigens, the same strains used on the 2010-2011 influenza vaccine. TIV recipients aged 6 to 35 months old received 0.25 mL intramuscularly and recipients aged 36 months and older received 0.5 mL. LAIV recipients received 0.2 mL by intranasal route, 0.1 mL per nostril. Blood samples were collected at four time points, on day zero prior to vaccination, and day 1, day 7 (range 6-8) and day 30 (range 27-33) post-vaccination.

Experimental Variables

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Controls

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Methods

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Additional Information

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Microarray
Illumina HumanHT-12 v4
140 Samples Loaded: 140
Human (Homo sapiens)
Whole Blood
Influenza vaccine
Sample Set Spreadsheet
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Samples Preview
Sample ID !Sample Title Gender tissue group race
GSM1257128 NCH-VK-73B_TIV_24h M whole blood TIV day1 A/Indian
GSM1257129 NCH-VK-84C_LAIV_D7 M whole blood LAIV day7 W
GSM1257130 NHC-VK-60D_TIV_D30 M whole blood TIV day30 W
GSM1257131 NCH-VK-82A_LAIV_D0 F whole blood LAIV day0 A/Chinese
GSM1257132 NCH-VK-58A_TIV_D0 F whole blood TIV day0 W
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File
sampleset4000036_sampleannotations_Group.csv
Sample Set Spreadsheet
sampleset4000036_sampleannotations_Group.csv
Sample Set Spreadsheet
Raw Signal
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Samples Viewer / Editor

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Sample ID !Sample Title Gender Tissue Group Race Vaccine Time point Age (years)
GSM1257128
NCH-VK-73B_TIV_24h
M
whole blood
TIV day1
A/Indian
TIV
D1
4.53
GSM1257129
NCH-VK-84C_LAIV_D7
M
whole blood
LAIV day7
W
LAIV
D7
5.94
GSM1257130
NHC-VK-60D_TIV_D30
M
whole blood
TIV day30
W
TIV
D30
13.07
GSM1257131
NCH-VK-82A_LAIV_D0
F
whole blood
LAIV day0
A/Chinese
LAIV
D0
12.68
GSM1257132
NCH-VK-58A_TIV_D0
F
whole blood
TIV day0
W
TIV
D0
13.87
GSM1257133
NCH-VK-81C_LAIV_D7
F
whole blood
LAIV day7
W
LAIV
D7
10.94
GSM1257134
NCH-VK-83B_LAIV_24h
F
whole blood
LAIV day1
W
LAIV
D1
9.09
GSM1257135
NCH-VK-79D_LAIV_D30
F
whole blood
LAIV day30
W
LAIV
D30
3.72
GSM1257136
NCH-VK-70D_TIV_D30
M
whole blood
TIV day30
W
TIV
D30
4.8
GSM1257137
NCH-VK-50D_TIV_D30
M
whole blood
TIV day30
Bi
TIV
D30
12.74
GSM1257138
NCH-VK-54C_LAIV_D7
M
whole blood
LAIV day7
W
LAIV
D7
14.36
GSM1257139
NCH-VK-75B_LAIV_24h
M
whole blood
LAIV day1
W
LAIV
D1
3.1
GSM1257140
NCH-VK-72C_TIV_D7
F
whole blood
TIV day7
W
TIV
D7
1.34
GSM1257141
NCH-VK-64C_LAIV_D7
M
whole blood
LAIV day7
W
LAIV
D7
13.71
GSM1257142
NCH-VK-58D_TIV_D30
F
whole blood
TIV day30
W
TIV
D30
13.94
GSM1257143
NCH-VK-62D_LAIV_D30
M
whole blood
LAIV day30
W
LAIV
D30
9.21
GSM1257144
NCH-VK-82D_LAIV_D30
F
whole blood
LAIV day30
A/Chinese
LAIV
D30
12.76
GSM1257145
NCH-VK-68C_LAIV_D7
M
whole blood
LAIV day7
Bi
LAIV
D7
14.29
GSM1257146
NCH-VK-64D_LAIV_D30
M
whole blood
LAIV day30
W
LAIV
D30
13.77
GSM1257147
NCH-VK-54D_LAIV_D30
M
whole blood
LAIV day30
W
LAIV
D30
14.43
GSM1257148
NCH-VK-59D_TIV_D30
F
whole blood
TIV day30
W
TIV
D30
13.21
GSM1257149
NCH-VK-83C_LAIV_D7
F
whole blood
LAIV day7
W
LAIV
D7
9.1
GSM1257150
NCH-VK-74A_LAIV_D0
F
whole blood
LAIV day0
W
LAIV
D0
3.58
GSM1257151
NCH-VK-71C_TIV_D7
F
whole blood
TIV day7
W
TIV
D7
2.97
GSM1257152
NCH-VK-62A_LAIV_D0
M
whole blood
LAIV day0
W
LAIV
D0
9.14
GSM1257153
NCH-VK-53B_TIV_24h
M
whole blood
TIV day1
W
TIV
D1
10.8
GSM1257154
NCH-VK-61A_LAIV_D0
F
whole blood
LAIV day0
W
LAIV
D0
13.66
GSM1257155
NCH-VK-58C_TIV_D7
F
whole blood
TIV day7
W
TIV
D7
13.88
GSM1257156
NCH-VK-56B_LAIV_24h
F
whole blood
LAIV day1
W
LAIV
D1
13.85
GSM1257157
NCH-VK-69B_TIV_24h
F
whole blood
TIV day1
A/Chinese
TIV
D1
11.86
GSM1257158
NCH-VK-80A_LAIV_D0
F
whole blood
LAIV day0
W
LAIV
D0
6.01
GSM1257159
NCH-VK-76D_TIV_D30
F
whole blood
TIV day30
W
TIV
D30
5
GSM1257160
NCH-VK-58B_TIV_24h
F
whole blood
TIV day1
W
TIV
D1
13.87
GSM1257161
NCH-VK-53D_TIV_D30
M
whole blood
TIV day30
W
TIV
D30
10.89
GSM1257162
NCH-VK-63D_TIV_D30
M
whole blood
TIV day30
W
TIV
D30
6.95
GSM1257163
NCH-VK-77D_LAIV_D30
M
whole blood
LAIV day30
W
LAIV
D30
3.48
GSM1257164
NCH-VK-51C_LAIV_D7
M
whole blood
LAIV day7
Bi
LAIV
D7
13.73
GSM1257165
NCH-VK-81B_LAIV_24h
F
whole blood
LAIV day1
W
LAIV
D1
10.93
GSM1257166
NCH-VK-83D_LAIV_D30
F
whole blood
LAIV day30
W
LAIV
D30
9.16
GSM1257167
NCH-VK-55A_TIV_D0
M
whole blood
TIV day0
W
TIV
D0
12.18
GSM1257168
NCH-VK-55D_TIV_D30
M
whole blood
TIV day30
W
TIV
D30
12.27
GSM1257169
NCH-VK-67A_LAIV_D0
F
whole blood
LAIV day0
W
LAIV
D0
11.64
GSM1257170
NCH-VK-66A_TIV_D0
F
whole blood
TIV day0
W
TIV
D0
13.98
GSM1257171
NCH-VK-81A_LAIV_D0
F
whole blood
LAIV day0
W
LAIV
D0
10.92
GSM1257172
NCH-VK-62B_LAIV_24h
M
whole blood
LAIV day1
W
LAIV
D1
9.14
GSM1257173
NCH-VK-52D_LAIV_D30
M
whole blood
LAIV day30
W
LAIV
D30
14.54
GSM1257174
NCH-VK-63A_TIV_D0
M
whole blood
TIV day0
W
TIV
D0
6.87
GSM1257175
NCH-VK-73C_TIV_D7
M
whole blood
TIV day7
A/Indian
TIV
D7
4.55
GSM1257176
NCH-VK-50C_TIV_D7
M
whole blood
TIV day7
Bi
TIV
D7
12.67
GSM1257177
NCH-VK-52A_LAIV_D0
M
whole blood
LAIV day0
W
LAIV
D0
14.45
GSM1257178
NCH-VK-82C_LAIV_D7
F
whole blood
LAIV day7
A/Chinese
LAIV
D7
12.7
GSM1257179
NCH-VK-66C_TIV_D7
F
whole blood
TIV day7
W
TIV
D7
14
GSM1257180
NCH-VK-67C_LAIV_D7
F
whole blood
LAIV day7
W
LAIV
D7
11.66
GSM1257181
NCH-VK-78D_TIV_D30
F
whole blood
TIV day30
W
TIV
D30
2.72
GSM1257182
NCH-VK-63C_TIV_D7
M
whole blood
TIV day7
W
TIV
D7
6.89
GSM1257183
NCH-VK-65D_LAIV_D30
F
whole blood
LAIV day30
W
LAIV
D30
14.68
GSM1257184
NCH-VK-61C_LAIV_D7
F
whole blood
LAIV day7
W
LAIV
D7
13.67
GSM1257185
NCH-VK-50B_TIV_24h
M
whole blood
TIV day1
Bi
TIV
D1
12.65
GSM1257186
NCH-VK-80D_LAIV_D30
F
whole blood
LAIV day30
W
LAIV
D30
6.09
GSM1257187
NCH-VK-52B_LAIV_24h
M
whole blood
LAIV day1
W
LAIV
D1
14.45
GSM1257188
NCH-VK-84B_LAIV_24h
M
whole blood
LAIV day1
W
LAIV
D1
5.92
GSM1257189
NCH-VK-51D_LAIV_D30
M
whole blood
LAIV day30
N
LAIV
D30
13.8
GSM1257190
NCH-VK-69D_TIV_D30
F
whole blood
TIV day30
A/Chinese
TIV
D30
11.94
GSM1257191
NCH-VK-79A_LAIV_D0
F
whole blood
LAIV day0
W
LAIV
D0
3.64
GSM1257192
NCH-VK-78C_TIV_D7
F
whole blood
TIV day7
W
TIV
D7
2.66
GSM1257193
NCH-VK-83A_LAIV_D0
F
whole blood
LAIV day0
W
LAIV
D0
9.08
GSM1257194
NCH-VK-52C_LAIV_D7
M
whole blood
LAIV day7
W
LAIV
D7
14.47
GSM1257195
NCH-VK-56D_LAIV_D30
F
whole blood
LAIV day30
W
LAIV
D30
13.92
GSM1257196
NCH-VK-78B_TIV_24h
F
whole blood
TIV day1
W
TIV
D1
2.64
GSM1257197
NCH-VK-61B_LAIV_24h
F
whole blood
LAIV day1
W
LAIV
D1
13.66
GSM1257198
NCH-VK-76B_TIV_24h
F
whole blood
TIV day1
W
TIV
D1
4.92
GSM1257199
NCH-VK-51A_LAIV_D0
M
whole blood
LAIV day0
Bi
LAIV
D0
13.71
GSM1257200
NCH-VK-53A_TIV_D0
M
whole blood
TIV day0
W
TIV
D0
10.8
GSM1257201
NCH-VK-69C_TIV_D7
F
whole blood
TIV day7
A/Chinese
TIV
D7
11.87
GSM1257202
NCH-VK-51B_LAIV_24h
M
whole blood
LAIV day1
Bi
LAIV
D1
13.71
GSM1257203
NCH-VK-74B_LAIV_24h
F
whole blood
LAIV day1
W
LAIV
D1
3.58
GSM1257204
NCH-VK-53C_TIV_D7
M
whole blood
TIV day7
W
TIV
D7
10.82
GSM1257205
NCH-VK-85D_TIV_D30
M
whole blood
TIV day30
Bi
TIV
D30
0.68
GSM1257206
NCH-VK-57D_TIV_D30
F
whole blood
TIV day30
W
TIV
D30
12.25
GSM1257207
NCH-VK-70C_TIV_D7
M
whole blood
TIV day7
W
TIV
D7
4.74
GSM1257208
NCH-VK-74C_LAIV_D7
F
whole blood
LAIV day7
W
LAIV
D7
3.6
GSM1257209
NCH-VK-80B_LAIV_24h
F
whole blood
LAIV day1
W
LAIV
D1
6.01
GSM1257210
NCH-VK-68D_LAIV_D30
M
whole blood
LAIV day30
Bi
LAIV
D30
14.35
GSM1257211
NCH-VK-69A_TIV_D0
F
whole blood
TIV day0
A/Chinese
TIV
D0
11.85
GSM1257212
NCH-VK-56C_LAIV_D7
F
whole blood
LAIV day7
W
LAIV
D7
13.87
GSM1257213
NHC-VK-60A_TIV_D0
M
whole blood
TIV day0
W
TIV
D0
12.99
GSM1257214
NCH-VK-78A_TIV_D0
F
whole blood
TIV day0
W
TIV
D0
2.64
GSM1257215
NCH-VK-85A_TIV_D0
M
whole blood
TIV day0
Bi
TIV
D0
0.52
GSM1257216
NCH-VK-57B_TIV_24h
F
whole blood
TIV day1
W
TIV
D1
12.18
GSM1257217
NCH-VK-72A_TIV_D0
F
whole blood
TIV day0
W
TIV
D0
1.32
GSM1257218
NCH-VK-79C_LAIV_D7
F
whole blood
LAIV day7
W
LAIV
D7
3.66
GSM1257219
NCH-VK-84A_LAIV_D0
M
whole blood
LAIV day0
W
LAIV
D0
5.92
GSM1257220
NCH-VK-80C_LAIV_D7
F
whole blood
LAIV day7
W
LAIV
D7
6.02
GSM1257221
NCH-VK-65B_LAIV_24h
F
whole blood
LAIV day1
W
LAIV
D1
14.61
GSM1257222
NCH-VK-82B_LAIV_24h
F
whole blood
LAIV day1
A/Chinese
LAIV
D1
12.68
GSM1257223
NHC-VK-60B_TIV_24h
M
whole blood
TIV day1
W
TIV
D1
12.99
GSM1257224
NCH-VK-64B_LAIV_24h
M
whole blood
LAIV day1
W
LAIV
D1
13.69
GSM1257225
NCH-VK-85C_TIV_D7
M
whole blood
TIV day7
Bi
TIV
D7
0.63
GSM1257226
NCH-VK-55B_TIV_24h
M
whole blood
TIV day1
W
TIV
D1
12.18
GSM1257227
NCH-VK-67B_LAIV_24h
F
whole blood
LAIV day1
W
LAIV
D1
11.65
GSM1257228
NCH-VK-56A_LAIV_D0
F
whole blood
LAIV day0
W
LAIV
D0
13.85
GSM1257229
NCH-VK-55C_TIV_D7
M
whole blood
TIV day7
W
TIV
D7
12.2
GSM1257230
NCH-VK-59B_TIV_24h
F
whole blood
TIV day1
W
TIV
D1
13.13
GSM1257231
NCH-VK-65C_LAIV_D7
F
whole blood
LAIV day7
W
LAIV
D7
14.63
GSM1257232
NCH-VK-77C_LAIV_D7
M
whole blood
LAIV day7
Bi
LAIV
D7
3.42
GSM1257233
NHC-VK-60C_TIV_D7
M
whole blood
TIV day7
W
TIV
D7
13.01
GSM1257234
NCH-VK-50A_TIV_D0
M
whole blood
TIV day0
Bi
TIV
D0
12.65
GSM1257235
NCH-VK-75A_LAIV_D0
M
whole blood
LAIV day0
W
LAIV
D0
3.1
GSM1257236
NCH-VK-81D_LAIV_D30
F
whole blood
LAIV day30
W
LAIV
D30
11.01
GSM1257237
NHC-VK-68A_LAIV_D0
M
whole blood
LAIV day0
Bi
LAIV
D0
14.27
GSM1257238
NCH-VK-61D_LAIV_D30
F
whole blood
LAIV day30
W
LAIV
D30
13.73
GSM1257239
NCH-VK-57C_TIV_D7
F
whole blood
TIV day7
W
TIV
D7
12.2
GSM1257240
NCH-VK-65A_LAIV_D0
F
whole blood
LAIV day0
W
LAIV
D0
14.61
GSM1257241
NCH-VK-64A_LAIV_D0
M
whole blood
LAIV day0
W
LAIV
D0
13.69
GSM1257242
NCH-VK-72B_TIV_24h
F
whole blood
TIV day1
W
TIV
D1
1.33
GSM1257243
NCH-VK-54B_LAIV_24h
M
whole blood
LAIV day1
W
LAIV
D1
14.35
GSM1257244
NCH-VK-67D_LAIV_D30
F
whole blood
LAIV day30
W
LAIV
D30
11.72
GSM1257245
NCH-VK-85B_TIV_24h
M
whole blood
TIV day1
Bi
TIV
D1
0.6
GSM1257246
NCH-VK-66B_TIV_24h
F
whole blood
TIV day1
W
TIV
D1
13.98
GSM1257247
NCH-VK-63B_TIV_24h
M
whole blood
TIV day1
W
TIV
D1
6.88
GSM1257248
NCH-VK-76A_TIV_D0
F
whole blood
TIV day0
W
TIV
D0
4.92
GSM1257249
NCH-VK-66D_TIV_D30
F
whole blood
TIV day30
W
TIV
D30
14.05
GSM1257250
NCH-VK-73D_TIV_D30
M
whole blood
TIV day30
A/Indian
TIV
D30
4.61
GSM1257251
NCH-VK-59A_TIV_D0
F
whole blood
TIV day0
W
TIV
D0
13.13
GSM1257252
NCH-VK-71A_TIV_D0
F
whole blood
TIV day0
W
TIV
D0
2.95
GSM1257253
NCH-VK-74D_LAIV_D30
F
whole blood
LAIV day30
W
LAIV
D30
3.66
GSM1257254
NCH-VK-59C_TIV_D7
F
whole blood
TIV day7
W
TIV
D7
13.15
GSM1257255
NCH-VK-77A_LAIV_D0
M
whole blood
LAIV day0
Bi
LAIV
D0
3.4
GSM1257256
NCH-VK-72D_TIV_D30
F
whole blood
TIV day30
W
TIV
D30
1.41
GSM1257257
NCH-VK-76C_TIV_D7
F
whole blood
TIV day7
W
TIV
D7
4.94
GSM1257258
NCH-VK-79B_LAIV_24h
F
whole blood
LAIV day1
W
LAIV
D1
3.64
GSM1257259
NCH-VK-57A_TIV_D0
F
whole blood
TIV day0
W
TIV
D0
12.18
GSM1257260
NCH-VK-62C_LAIV_D7
M
whole blood
LAIV day7
W
LAIV
D7
9.16
GSM1257261
NCH-VK-68B_LAIV_24h
M
whole blood
LAIV day1
Bi
LAIV
D1
14.28
GSM1257262
NCH-VK-73A_TIV_D0
M
whole blood
TIV day0
A/Indian
TIV
D0
4.53
GSM1257263
NCH-VK-84D_LAIV_D30
M
whole blood
LAIV day30
W
LAIV
D30
6
GSM1261854
NCH-VK-86A_LAIV_D0
M
whole blood
LAIV day0
W
LAIV
D0
3.5
GSM1261855
NCH-VK-86B_LAIV_24h
M
whole blood
LAIV day1
W
LAIV
D1
3.51
GSM1261856
NCH-VK-86C_LAIV_D7
M
whole blood
LAIV day7
W
LAIV
D7
3.52
GSM1261857
NCH-VK-86D_LAIV_D30
M
whole blood
LAIV day30
W
LAIV
D30
3.58

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