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H3N2 influenza infection elicits more cross-reactive and less clonally expanded anti-hemagglutinin antibodies than influenza vaccination.

Moody MA, Zhang R, Walter EB, Woods CW, Ginsburg GS, McClain MT, Denny TN, Chen X, Munshaw S, Marshall DJ, Whitesides JF, Drinker MS, Amos JD, Gurley TC, Eudailey JA, Foulger A, DeRosa KR, Parks R, Meyerhoff RR, Yu JS, Kozink DM, Barefoot BE, Ramsburg EA, Khurana S, Golding H, Vandergrift NA, Alam SM, Tomaras GD, Kepler TB, Kelsoe G, Liao HX, Haynes BF - PLoS ONE (2011)

Bottom Line: In contrast, a history of recent seasonal trivalent vaccine in younger adults was not associated with protection.Plasma cell-derived anti-HA antibodies from TIV subjects showed more evidence of clonal expansion compared with antibodies from EI subjects.This broad reactivity was not detected in post-infection plasma suggesting this broadly reactive clonal lineage was not immunodominant in this subject.

View Article: PubMed Central - PubMed

Affiliation: Duke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, United States of America. moody007@mc.duke.edu

ABSTRACT

Background: During the recent H1N1 influenza pandemic, excess morbidity and mortality was seen in young but not older adults suggesting that prior infection with influenza strains may have protected older subjects. In contrast, a history of recent seasonal trivalent vaccine in younger adults was not associated with protection.

Methods and findings: To study hemagglutinin (HA) antibody responses in influenza immunization and infection, we have studied the day 7 plasma cell repertoires of subjects immunized with seasonal trivalent inactivated influenza vaccine (TIV) and compared them to the plasma cell repertoires of subjects experimentally infected (EI) with influenza H3N2 A/Wisconsin/67/2005. The majority of circulating plasma cells after TIV produced influenza-specific antibodies, while most plasma cells after EI produced antibodies that did not react with influenza HA. While anti-HA antibodies from TIV subjects were primarily reactive with single or few HA strains, anti-HA antibodies from EI subjects were isolated that reacted with multiple HA strains. Plasma cell-derived anti-HA antibodies from TIV subjects showed more evidence of clonal expansion compared with antibodies from EI subjects. From an H3N2-infected subject, we isolated a 4-member clonal lineage of broadly cross-reactive antibodies that bound to multiple HA subtypes and neutralized both H1N1 and H3N2 viruses. This broad reactivity was not detected in post-infection plasma suggesting this broadly reactive clonal lineage was not immunodominant in this subject.

Conclusion: The presence of broadly reactive subdominant antibody responses in some EI subjects suggests that improved vaccine designs that make broadly reactive antibody responses immunodominant could protect against novel influenza strains.

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Related in: MedlinePlus

Characterization of peripheral blood plasmacytosis 7 days after TIV or EI.A. Peripheral blood B cells (CD3/14/16/235a− CD19+) stained for plasma cell markers (CD3/14/16/235a− CD19+ CD20−/lo CD27hi CD38hi); points shown are percentage of B cells that were plasma cells. TIV mean 2.75%±0.90%; EI mean 2.26±0.74%; two-tailed t test, p = 0.68. B. Human rmAbs derived from sorted plasma cells tested for reactivity. From TIV subjects, 252/404 rmAbs (62.4%) reacted with ≥1 influenza antigen (blue wedge), 152/404 (37.6%) did not react with any tested rHA or split-virus antigen (gray wedge). From EI subjects, 37/451 rmAbs (8.2%) reacted with ≥1 influenza antigen (tested vs. TIV, χ2 = 279.5, p<0.0001), 414/451 (91.8%) did not react with any tested rHA or split-virus antigen. C. Human rmAbs membership in clonal lineages. From TIV subjects, 175/404 (43.3%) rmAbs were members of 46 clonal lineages (red wedge); from EI subjects, 28/451 (6.2%) rmAbs were members of 12 clonal lineages (χ2 = 162.1, p<0.0001).
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pone-0025797-g001: Characterization of peripheral blood plasmacytosis 7 days after TIV or EI.A. Peripheral blood B cells (CD3/14/16/235a− CD19+) stained for plasma cell markers (CD3/14/16/235a− CD19+ CD20−/lo CD27hi CD38hi); points shown are percentage of B cells that were plasma cells. TIV mean 2.75%±0.90%; EI mean 2.26±0.74%; two-tailed t test, p = 0.68. B. Human rmAbs derived from sorted plasma cells tested for reactivity. From TIV subjects, 252/404 rmAbs (62.4%) reacted with ≥1 influenza antigen (blue wedge), 152/404 (37.6%) did not react with any tested rHA or split-virus antigen (gray wedge). From EI subjects, 37/451 rmAbs (8.2%) reacted with ≥1 influenza antigen (tested vs. TIV, χ2 = 279.5, p<0.0001), 414/451 (91.8%) did not react with any tested rHA or split-virus antigen. C. Human rmAbs membership in clonal lineages. From TIV subjects, 175/404 (43.3%) rmAbs were members of 46 clonal lineages (red wedge); from EI subjects, 28/451 (6.2%) rmAbs were members of 12 clonal lineages (χ2 = 162.1, p<0.0001).

Mentions: As described [14] we analyzed PBMC for the presence of plasma cells (CD3/14/16/235a− CD19+ CD20−/lo CD27hi CD38hi) seven days after TIV or EI. There was no difference in plasma cell frequencies between five TIV subjects and six EI subjects as a percentage of the total B cell population (CD3/14/16/235a− CD19+) in PBMC [TIV mean 2.75%±0.90%; EI mean 2.26±0.74%; two-tailed t test, p = 0.68] (Fig. 1A; Fig. S2 online).


H3N2 influenza infection elicits more cross-reactive and less clonally expanded anti-hemagglutinin antibodies than influenza vaccination.

Moody MA, Zhang R, Walter EB, Woods CW, Ginsburg GS, McClain MT, Denny TN, Chen X, Munshaw S, Marshall DJ, Whitesides JF, Drinker MS, Amos JD, Gurley TC, Eudailey JA, Foulger A, DeRosa KR, Parks R, Meyerhoff RR, Yu JS, Kozink DM, Barefoot BE, Ramsburg EA, Khurana S, Golding H, Vandergrift NA, Alam SM, Tomaras GD, Kepler TB, Kelsoe G, Liao HX, Haynes BF - PLoS ONE (2011)

Characterization of peripheral blood plasmacytosis 7 days after TIV or EI.A. Peripheral blood B cells (CD3/14/16/235a− CD19+) stained for plasma cell markers (CD3/14/16/235a− CD19+ CD20−/lo CD27hi CD38hi); points shown are percentage of B cells that were plasma cells. TIV mean 2.75%±0.90%; EI mean 2.26±0.74%; two-tailed t test, p = 0.68. B. Human rmAbs derived from sorted plasma cells tested for reactivity. From TIV subjects, 252/404 rmAbs (62.4%) reacted with ≥1 influenza antigen (blue wedge), 152/404 (37.6%) did not react with any tested rHA or split-virus antigen (gray wedge). From EI subjects, 37/451 rmAbs (8.2%) reacted with ≥1 influenza antigen (tested vs. TIV, χ2 = 279.5, p<0.0001), 414/451 (91.8%) did not react with any tested rHA or split-virus antigen. C. Human rmAbs membership in clonal lineages. From TIV subjects, 175/404 (43.3%) rmAbs were members of 46 clonal lineages (red wedge); from EI subjects, 28/451 (6.2%) rmAbs were members of 12 clonal lineages (χ2 = 162.1, p<0.0001).
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Related In: Results  -  Collection

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pone-0025797-g001: Characterization of peripheral blood plasmacytosis 7 days after TIV or EI.A. Peripheral blood B cells (CD3/14/16/235a− CD19+) stained for plasma cell markers (CD3/14/16/235a− CD19+ CD20−/lo CD27hi CD38hi); points shown are percentage of B cells that were plasma cells. TIV mean 2.75%±0.90%; EI mean 2.26±0.74%; two-tailed t test, p = 0.68. B. Human rmAbs derived from sorted plasma cells tested for reactivity. From TIV subjects, 252/404 rmAbs (62.4%) reacted with ≥1 influenza antigen (blue wedge), 152/404 (37.6%) did not react with any tested rHA or split-virus antigen (gray wedge). From EI subjects, 37/451 rmAbs (8.2%) reacted with ≥1 influenza antigen (tested vs. TIV, χ2 = 279.5, p<0.0001), 414/451 (91.8%) did not react with any tested rHA or split-virus antigen. C. Human rmAbs membership in clonal lineages. From TIV subjects, 175/404 (43.3%) rmAbs were members of 46 clonal lineages (red wedge); from EI subjects, 28/451 (6.2%) rmAbs were members of 12 clonal lineages (χ2 = 162.1, p<0.0001).
Mentions: As described [14] we analyzed PBMC for the presence of plasma cells (CD3/14/16/235a− CD19+ CD20−/lo CD27hi CD38hi) seven days after TIV or EI. There was no difference in plasma cell frequencies between five TIV subjects and six EI subjects as a percentage of the total B cell population (CD3/14/16/235a− CD19+) in PBMC [TIV mean 2.75%±0.90%; EI mean 2.26±0.74%; two-tailed t test, p = 0.68] (Fig. 1A; Fig. S2 online).

Bottom Line: In contrast, a history of recent seasonal trivalent vaccine in younger adults was not associated with protection.Plasma cell-derived anti-HA antibodies from TIV subjects showed more evidence of clonal expansion compared with antibodies from EI subjects.This broad reactivity was not detected in post-infection plasma suggesting this broadly reactive clonal lineage was not immunodominant in this subject.

View Article: PubMed Central - PubMed

Affiliation: Duke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, United States of America. moody007@mc.duke.edu

ABSTRACT

Background: During the recent H1N1 influenza pandemic, excess morbidity and mortality was seen in young but not older adults suggesting that prior infection with influenza strains may have protected older subjects. In contrast, a history of recent seasonal trivalent vaccine in younger adults was not associated with protection.

Methods and findings: To study hemagglutinin (HA) antibody responses in influenza immunization and infection, we have studied the day 7 plasma cell repertoires of subjects immunized with seasonal trivalent inactivated influenza vaccine (TIV) and compared them to the plasma cell repertoires of subjects experimentally infected (EI) with influenza H3N2 A/Wisconsin/67/2005. The majority of circulating plasma cells after TIV produced influenza-specific antibodies, while most plasma cells after EI produced antibodies that did not react with influenza HA. While anti-HA antibodies from TIV subjects were primarily reactive with single or few HA strains, anti-HA antibodies from EI subjects were isolated that reacted with multiple HA strains. Plasma cell-derived anti-HA antibodies from TIV subjects showed more evidence of clonal expansion compared with antibodies from EI subjects. From an H3N2-infected subject, we isolated a 4-member clonal lineage of broadly cross-reactive antibodies that bound to multiple HA subtypes and neutralized both H1N1 and H3N2 viruses. This broad reactivity was not detected in post-infection plasma suggesting this broadly reactive clonal lineage was not immunodominant in this subject.

Conclusion: The presence of broadly reactive subdominant antibody responses in some EI subjects suggests that improved vaccine designs that make broadly reactive antibody responses immunodominant could protect against novel influenza strains.

Show MeSH
Related in: MedlinePlus