Cell-Mediated Proteomics, and Serological and Mucosal Humoral Immune Responses after Seasonal Influenza Immunization: Characterization of Serological Responders and Non-Responders
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Population and Vaccine
2.2. Total Serum Immunoglobulin A, G and M
2.3. Isolation of Peripheral Blood Mononuclear Cells
2.4. Stimulation of Peripheral Blood Mononuclear Cells with Influenza Vaccine
2.5. Haemagglutination Inhibition Test, HAI
2.6. Influenza-Specific Mucosal Immunoglobulin A (IgA)
2.7. Proximity Extension Assay
2.8. Statistical Analysis
3. Results
3.1. Study Population
3.2. Total Serum Immunoglobulins and Specific Mucosal Immunoglobulin A
3.3. Protein Profiling of Supernatants from PBMCs Stimulated with Influenza Vaccine VaxigripTetra
3.4. Characterisation of Influenza Immunisation Responders and Non-Responders
3.5. Immunosuppressive Medication
3.6. Vaccine Breakthrough
3.7. Age-Associated Immune Response
3.8. Comparison of PBMC Stimulations Using Fresh and Cryopreserved Cells
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Responders | Non-Responders | |||
---|---|---|---|---|
Influenza Strain, Median (Range) | One Month (n = 51) | Six Months (n = 29) | One Month (n = 22) | Six Months (n = 44) |
A/H1N1/09pdm | 160 (5–20,480) | 120 (5–10,240) | 160 (60–5120) | 160 (20–1280) |
A/H3N2/HK | 80 (5–10,240) | 60 (5–5120) | 80 (5–5120) | 80 (5–2560) |
B/60/Brisbane2008 | 160 (5–5120) | 100 (5–2560) | 320 (40–1280) | 160 (20–640) |
Variable | Responders | Non-Responders | p-Value | Total |
---|---|---|---|---|
n (%) | 51 (70) | 22 (30) | 73 (100) | |
Sex n (%) | ||||
Female | 37 (73) | 15 (68) | 52 (71) | |
Male | 14 (27) | 7 (32) | 0.781 | 21 (29) |
Age (yrs) | ||||
Mean (SD) | 70 (18) | 67 (15) | 69 (17) | |
Median (Q1–Q3) | 77 (61–84) | 73 (61–81) | 0.243 | 76 (61–81) |
Age categories n (%) | ||||
≤65 | 14 (27) | 9 (41) | 23 (32) | |
>65 | 37 (73) | 13 (59) | 0.282 | 50 (68) |
Height (cm) | ||||
Mean (SD) | 168 (9) | 170 (7) | 168 (9) | |
Median (Q1–Q3) | 167 (160–175) | 170 (164–175) | 0.367 | 169 (161–175) |
Weight (kg) | ||||
Mean (SD) | 76 (15) | 77 (18) | 76 (16) | |
Median (Q1–Q3) | 75 (66–86) | 75 (67–87) | 0.967 | 75 (66–86) |
BMI (kg m−2) | ||||
Mean (SD) | 27 (4) | 27 (6) | 27 (5) | |
Median (Q1–Q3) | 27 (24–29) | 25 (24–30) | 0.539 | 27 (24–29) |
Diabetes | ||||
No | 43 (84) | 16 (76) | 59 (82) | |
Yes | 8 (16) | 5 (24) | 0.504 | 13 (18) |
Lung disease | ||||
No | 45 (88) | 20 (95) | 65 (90) | |
Yes | 5 (10) | 1 (5) | 6 (8) | |
Missing | 1 (2) | 0 (0) | 0.662 | 1 (1) |
Upper respiratory tract infections in last five years | ||||
0–3 | 45 (88) | 18 (86) | 63 (88) | |
4–6 | 5 (10) | 1 (5) | 6 (8) | |
>6 | 0 (0) | 1 (5) | 1 (1) | |
Missing | 1 (2) | 1 (5) | 0.233 | 2 (3) |
Immune-suppressive medication | ||||
No | 50 (98) | 21 (100) | 71 (99) | |
Yes | 1 (2) | 0 (0) | >0.99 | 1 (1) |
Side effects | ||||
No | 46 (90) | 19 (86) | 65 (89) | |
Yes | 5 (10) | 3 (14) | 0.691 | 8 (11) |
ONE MONTH | ||||
---|---|---|---|---|
Variable | Responders | Non-Responders | p-Value | Total |
n | 51 | 22 | 73 | |
Total serum IgA (g/L) | ||||
Mean (SD) | 2.56 (1.09) | 2.54 (1.01) | 2.55 (1.06) | |
Median (Q1–Q3) | 2.5 (1.6–3.3) | 2.7 (1.9–2.9) | 0.891 | 2.6 (1.9–3.0) |
Total serum IgG (g/L) | ||||
Mean (SD) | 10.7 (2.7) | 11.1 (2.0) | 10.8 (2.5) | |
Median (Q1–Q3) | 11 (9–13) | 11 (10–12) | 0.587 | 11 (10–12) |
Total serum IgM (g/L) | ||||
Mean (SD) | 0.88 (0.71) | 1.03 (0.45) | 0.93 (0.64) | |
Median (Q1–Q3) | 0.7 (0.5–1.0) | 0.9 (0.7–1.3) | 0.053 | 0.8 (0.6–1.2) |
Mucosal IgA A/Brisbane | ||||
Mean (SD) | 22.1 (34.1) | 17.7 (17.3) | 20.7 (29.6) | |
Median (Q1–Q3) | 12.8 (7.0–21.3) | 11.5 (6.6–22.2) | 0.994 | 12.6 (7.0–22.0) |
Mucosal IgA A/Kansas | ||||
Mean (SD) | 22.6 (27.8) | 19.0 (17.1) | 21.4 (24.7) | |
Median (Q1–Q3) | 14.5 (8.3–22.9) | 11.6 (8.7–22.2) | 0.865 | 13.8 (8.5–22.6) |
Mucosal IgA B/Brisbane-like | ||||
Mean (SD) | 20.4 (18.5) | 21.0 (19.8) | 20.6 (18.8) | |
Median (Q1–Q3) | 15.0 (8.0–25.7) | 12.6 (8.2–32.2) | 0.960 | 14.2 (8.2–27.6) |
Ratio Mucosal IgA A/Brisbane | ||||
Mean (SD) | 1.81 (1.94) | 1.69 (0.89) | 1.77 (1.67) | |
Median (Q1–Q3) | 1.2 (0.8–2.2) | 1.7 (0.9–2.5) | 0.365 | 1.2 (0.8–2.3) |
Ratio Mucosal IgA A/Kansas | ||||
Mean (SD) | 3.21 (9.44) | 2.10 (1.42) | 2.84 (7.71) | |
Median (Q1–Q3) | 1.4 (0.9–2.0) | 1.6 (1.1–2.8) | 0.408 | 1.4 (0.9–2.4) |
Ratio Mucosal IgA B/Brisbane-like | ||||
Mean (SD) | 2.96 (5.15) | 2.03 (1.61) | 2.66 (4.35) | |
Median (Q1–Q3) | 1.3 (0.9–2.2) | 1.6 (0.9–2.7) | 0.720 | 1.4 (0.9–2.3) |
Responders | Univariate Logistic Regression | Multivariate Logistic Regression | |||||
---|---|---|---|---|---|---|---|
Parameter | Total | n | (%) | OR (95% Conf Int) | p-Value | OR (95% Conf Int) | p-Value |
Sex | |||||||
Female | 52 | 37 | 71 | 1.00 | 1.00 | ||
Male | 21 | 14 | 67 | 0.81 (0.27–2.45) | 0.707 | 0.94 (0.22–4.03) | 0.936 |
Age categories n (%) | |||||||
≤65 | 23 | 14 | 61 | 1.00 | 1.00 | ||
>65 | 50 | 37 | 74 | 1.83 (0.63–5.33) | 0.263 | 0.37 (0.07–2.04) | 0.249 |
Total IgM (g/L) | |||||||
≤0.5 | 15 | 14 | 93 | 1.00 | 1.00 | ||
0.6–0.8 | 26 | 19 | 73 | 0.54 (0.33–0.90) | 0.49 (0.27–0.90) | ||
0.9–1.1 | 12 | 7 | 58 | 0.29 (0.11–0.80) | 0.24 (0.07–0.81) | ||
>1.1 | 20 | 11 | 55 | 0.16 (0.04–0.72) | 0.017 | 0.12 (0.02–0.72) | 0.022 |
CCL19 | |||||||
≤−1.1 | 19 | 13 | 68 | 1.00 | |||
−1.2–0.6 | 18 | 18 | 100 | 0.62 (0.38–1.00) | |||
0.7–2.0 | 17 | 11 | 65 | 0.38 (0.15–0.99) | |||
>2.0 | 19 | 9 | 47 | 0.24 (0.06–0.99) | 0.048 | - | |
CD70 | |||||||
≤−0.3 | 18 | 13 | 72 | 1.00 | |||
−0.4–0.2 | 19 | 17 | 89 | 0.70 (0.43–1.13) | |||
0.3–0.9 | 19 | 11 | 58 | 0.49 (0.19–1.28) | |||
>0.9 | 17 | 10 | 59 | 0.34 (0.08–1.45) | 0.143 | - | |
CXCL13 | |||||||
≤−1.7 | 18 | 9 | 50 | 1.00 | 1.00 | ||
−1.8–−0.4 | 18 | 12 | 67 | 1.48 (0.92–2.38) | 2.06 (1.09–3.88) | ||
−0.5–1.1 | 18 | 17 | 94 | 2.20 (0.86–5.66) | 4.24 (1.20–15.02) | ||
>1.1 | 19 | 13 | 68 | 3.26 (0.79–13.46) | 0.100 | 8.73 (1.31–58.19) | 0.026 |
IL13 | |||||||
≤−0.9 | 19 | 18 | 95 | 1.00 | |||
−0.8–−0.06 | 17 | 10 | 59 | 0.61 (0.38–0.98) | |||
−0.05–0.7 | 17 | 11 | 65 | 0.37 (0.14–0.96) | |||
>0.8 | 20 | 12 | 60 | 0.23 (0.05–0.95) | 0.042 | - | |
GZMB | |||||||
≤−135 | 19 | 17 | 89 | 1.00 | 1.00 | ||
−134–14 | 17 | 12 | 71 | 0.61 (0.38–0.99) | 0.42 (0.19–0.89) | ||
15–259 | 19 | 11 | 58 | 0.37 (0.14–0.98) | 0.17 (0.04–0.80) | ||
>259 | 18 | 11 | 61 | 0.23 (0.05–0.98) | 0.046 | 0.07 (0.01–0.72) | 0.025 |
IL12 | |||||||
≤−0.5 | 18 | 15 | 83 | 1.00 | 1.00 | ||
−0.4–0.4 | 18 | 12 | 67 | 0.63 (0.39–1.02) | 0.43 (0.21–0.92) | ||
0.5–1.2 | 18 | 15 | 83 | 0.40 (0.15–1.05) | 0.19 (0.04–0.84) | ||
>1.2 | 19 | 9 | 47 | 0.25 (0.06–1.07) | 0.061 | 0.08 (0.01–0.77) | 0.029 |
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Carlsson, H.; Brudin, L.; Serrander, L.; Hinkula, J.; Tjernberg, I. Cell-Mediated Proteomics, and Serological and Mucosal Humoral Immune Responses after Seasonal Influenza Immunization: Characterization of Serological Responders and Non-Responders. Vaccines 2024, 12, 303. https://doi.org/10.3390/vaccines12030303
Carlsson H, Brudin L, Serrander L, Hinkula J, Tjernberg I. Cell-Mediated Proteomics, and Serological and Mucosal Humoral Immune Responses after Seasonal Influenza Immunization: Characterization of Serological Responders and Non-Responders. Vaccines. 2024; 12(3):303. https://doi.org/10.3390/vaccines12030303
Chicago/Turabian StyleCarlsson, Hanna, Lars Brudin, Lena Serrander, Jorma Hinkula, and Ivar Tjernberg. 2024. "Cell-Mediated Proteomics, and Serological and Mucosal Humoral Immune Responses after Seasonal Influenza Immunization: Characterization of Serological Responders and Non-Responders" Vaccines 12, no. 3: 303. https://doi.org/10.3390/vaccines12030303