Baseline Levels of Influenza-Specific B Cells and T Cell Responses Modulate Human Immune Responses to Swine Variant Influenza A/H3N2 Vaccine
Abstract
1. Introduction
2. Materials and Methods
2.1. Study Population
2.2. Viruses and Antigens
2.3. Peripheral Blood Mononuclear Cell Isolation
2.4. Serum Hemagglutination Inhibition (HAI) and Neutralization (Neut) Antibody Assays
2.5. Antibody-Secreting Cells (Plasmablasts) Assay
2.6. H3N2 Specific CD4+ T Cells by Intracellular Cytokine and CD154 Staining Assay
2.7. Memory B Cell (MBC) Assay
2.8. Statistical Methods
3. Results
3.1. Demographics
3.2. Preexisting Cross-Reactive Antibody and Expansion of the Antibody Response
3.3. Plasmablast Responses Correlated with HAI and Neut Titers and Were Detected against Seasonal H3N2 Antigens
3.4. Expansion of Circulating Antiviral CD4+ T Cells against H3N2v Correlated with Antibody Responses
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Characteristics | Values (Sample Size n = 25) |
---|---|
Age | |
Mean (SD) | 38.4 (14.4) |
Median [Min, Max] | 30.0 [22.0, 63.0] |
Gender—n (%) | |
Female | 11 (44) |
Male | 14 (56) |
Race—n (%) | |
Asian | 4 (16) |
Black/African American | 8 (32) |
Multi-Racial | 1 (4) |
White | 12 (48) |
Prior IIV 1 Receipt—n (%) | |
None | 5 (20) |
2012/13 IIV only | 1 (4) |
2011/12 IIV only | 7 (28) |
Both 2011/12 + 2012/13 IIV | 11 (44) |
Unknown prior IIV | 1 (4) |
Antibody Titers | Measured Metric | Day 0 (Pre-Vaccination) | Day 8 (Post Vaccination 1) | Day 21 (Post Vaccination 1, Immediately Pre-Vaccination 2) | Day 29 (Day 8 Post Vaccination 2) | Day 42 (Day 21 Post Vaccination 2) |
---|---|---|---|---|---|---|
Hemagglutination Inhibition (HAI) | Geometric Mean Titer (95% CI) | 27.5 (19.8, 38.3) | 91.9 (59.1, 142.8) | 117.9 (79.8, 174.2) | 126.4 (81.7, 195.6) | 135.5 (86.2, 213.0) |
Seroconversion 1—n (%) | NA | 13 (52.0) | 14 (56.0) | 13 (52.0) | 13 (52.0) | |
Neutralizing Antibody (Neut) | Geometric Mean Titer (95% CI) | 28.5 (16.0, 50.7) | 178.0 (103.6, 306.0) | 285.5 (162.2, 502.5) | 276.9 (157.8, 486.1) | 258.3 (149.7, 445.6) |
Seroconversion 1—n (%) | NA | 12 (48.0) | 13 (52.0) | 13 (52.0) | 13 (52.0) |
Measured Metric | IgG | IgA | ||||
---|---|---|---|---|---|---|
Strains | H3N2v Minnesota/2010 | H3N2 Perth/2009 | H3N2 Victoria/2011 | H3N2v Minnesota/2010 | H3N2 Perth/2009 | H3N2 Victoria/2011 |
Median (min, max) | 162 (0, 9477) | 9.0 (0, 1377) | 9.0 (0, 2187) | 30.0 (0, 509) | 0.0 (0, 126) | 0.0 (0, 99) |
Geometric Mean (95% CI) | 204.7 (104.2, 402.2) | 58.0 (20.4,164.7) | 84.0 (32.1, 219.9) | 56.1 (30.8, 101.8) | 23.7 (12.9, 43.4) | 21.2 (9.1, 49.3) |
Number of Subjects with a Positive Response (%) | 22 (88) | 14 (56) | 13 (52) | 20 (80) | 9 (36) | 7 (28) |
Plasmablasts | Hemagglutination Inhibition Antibody (p-Value) | Neutralizing Antibody (p-Value) |
---|---|---|
IgG | 0.469 (0.018) | 0.417 (0.038) |
IgA | 0.647 (<0.001) | 0.457 (0.021) |
Measured Metrics | Hemagglutination Inhibition Titer (p-Value) | Neutralizing Antibody Titer (p-Value) | ||||||
---|---|---|---|---|---|---|---|---|
Days | Day 8 | Day 21 | Day 29 | Day 42 | Day 8 | Day 21 | Day 29 | Day 42 |
CD154, IFN-γ, IL-2 or IL-21 expression CD4+ T-Cells on Day 0 | −0.293 (0.155) | −0.307 (0.135) | −0.290 (0.159) | −0.207 (0.321) | 0.169 (0.421) | −0.216 (0.300) | −0.239 (0.249) | −0.267 (0.197) |
Measured Metrics | Hemagglutination Inhibition Titer (p-Value) | Neutralizing Antibody Titer (p-Value) | ||||||
---|---|---|---|---|---|---|---|---|
CD154, IFN-γ, IL-2 or IL-21 expression CD4+ T Cells change from baseline (Day 0) | Day 8 | Day 21 | Day 29 | Day 42 | Day 8 | Day 21 | Day 29 | Day 42 |
Day 8–Day 0 | 0.582 (0.002) | 0.649 (<0.001) | 0.526 (0.007) | 0.265 (0.200) | 0.621 (<0.001) | 0.859 (<0.001) | 0.870 (<0.001) | 0.602 (<0.001) |
Day 21–Day 0 | 0.667 (<0.001) | 0.542 (0.005) | 0.295 (0.153) | 0.865 (<0.001) | 0.874 (<0.001) | 0.618 (<0.001) | ||
Day 29–Day 0 | 0.525 (0.008) | 0.279 (0.187) | 0.909 (<0.001) | 0.687 (<0.001) | ||||
Day 42–Day 0 | 0.280 (0.196) | 0.679 (<0.001) |
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Lai, L.; Rouphael, N.; Xu, Y.; Sherman, A.C.; Edupuganti, S.; Anderson, E.J.; Lankford-Turner, P.; Wang, D.; Keitel, W.; McNeal, M.M.; et al. Baseline Levels of Influenza-Specific B Cells and T Cell Responses Modulate Human Immune Responses to Swine Variant Influenza A/H3N2 Vaccine. Vaccines 2020, 8, 126. https://doi.org/10.3390/vaccines8010126
Lai L, Rouphael N, Xu Y, Sherman AC, Edupuganti S, Anderson EJ, Lankford-Turner P, Wang D, Keitel W, McNeal MM, et al. Baseline Levels of Influenza-Specific B Cells and T Cell Responses Modulate Human Immune Responses to Swine Variant Influenza A/H3N2 Vaccine. Vaccines. 2020; 8(1):126. https://doi.org/10.3390/vaccines8010126
Chicago/Turabian StyleLai, Lilin, Nadine Rouphael, Yongxian Xu, Amy C. Sherman, Srilatha Edupuganti, Evan J. Anderson, Pamela Lankford-Turner, Dongli Wang, Wendy Keitel, Monica M. McNeal, and et al. 2020. "Baseline Levels of Influenza-Specific B Cells and T Cell Responses Modulate Human Immune Responses to Swine Variant Influenza A/H3N2 Vaccine" Vaccines 8, no. 1: 126. https://doi.org/10.3390/vaccines8010126
APA StyleLai, L., Rouphael, N., Xu, Y., Sherman, A. C., Edupuganti, S., Anderson, E. J., Lankford-Turner, P., Wang, D., Keitel, W., McNeal, M. M., Cross, K., Hill, H., Bellamy, A. R., & Mulligan, M. J. (2020). Baseline Levels of Influenza-Specific B Cells and T Cell Responses Modulate Human Immune Responses to Swine Variant Influenza A/H3N2 Vaccine. Vaccines, 8(1), 126. https://doi.org/10.3390/vaccines8010126