Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2017 Sep 12;35(38):5163-5171.
doi: 10.1016/j.vaccine.2017.07.115. Epub 2017 Aug 12.

Plasma cell and serum antibody responses to influenza vaccine in preterm and full-term infants

Carl T D'Angio  1 , Claire P Wyman  2 , Ravi S Misra  2 , Jessica L Halliley  3 , Hongyue Wang  4 , Julianne E Hunn  2 , Caitlin M Fallone  2 , F Eun-Hyung Lee  5
Affiliations

Plasma cell and serum antibody responses to influenza vaccine in preterm and full-term infants

Carl T D'Angio et al. Vaccine. .

Abstract

Background: Preterm (PT) infants are at greater risk for severe influenza infection and experience decrements in long-term antibody responses to vaccines. This may related to defects in antibody secreting cell (ASC) generation.

Objective: To investigate the relationships among the frequencies of influenza-specific antibody secreting cells, ASC numbers and subsets, and antibody responses to influenza vaccines (IV) among PT and full-term (FT) infants.

Design/methods: We enrolled 11 former PT (≤32weeks' gestation, ≤1500 g' birth weight) and 11FT infants, 6-17months of age, receiving their first influenza immunizations. Infants received two doses of inactivated trivalent (T)IV or quadrivalent (Q)IV during the 2012-2013 and 2013-2014 influenza seasons, respectively, at 0 and 28days, and blood was drawn at 0, 10, 35, and 56days and 9months. Vaccine-specific antibody was measured by hemagglutination inhibition (HAI) at 0 and 56days and 9months, vaccine-specific ASC numbers by enzyme linked immunospot (ELISPOT) at 10 and 35days, and ASC subsets by flow cytometry at 0, 10 and 35days.

Results: PT infants had post-vaccine HAI titers to all 4 vaccine strains at least equal to FT infants at 56days and 9months after beginning immunization. Influenza-specific ASC ELISPOT responses at 35days were higher among PT than FT infants (median 100 v. 30 per 106 PBMC, p=0.04). ASC numbers at 35days were positively correlated with serum HAI titers at 56days (ρ=0.50-0.80). There were no statistical differences between PT and FT infants in the frequency of five ASC subsets and no specific ASC subset correlated with durability of serum antibody titers.

Conclusions: Influenza-specific ASC numbers in both FT and PT infants correlated with peak antibody titers, but ASC subsets did not correlate with durability of antibody response.

Keywords: Antibody titer; Antibody-secreting cell; Influenza vaccine; Plasma cell; Premature infant.

PubMed Disclaimer

Conflict of interest statement

Conflicts of interest: None

Figures

Figure 1
Figure 1
Schematic of study design. TIV = Trivalent influenza vaccine, QIV = quadrivalent influenza vaccine. Arrows denote visits. X = blood draw performed for indicated analysis.
Figure 2
Figure 2
Hemagglutination inhibition (HAI) titers. Serum was collected and analyzed at Visit 1 (0 days), Visit 5 (56 days) and Visit 6 (9 months). Pre-vaccine titers (Visit 1) were available for 7 preterm (PT) and all full-term (FT) infants and post-vaccine titers (Visits 5 and 6) available for all PT and 8 FT infants. B Yam = B/Yamagata. B Vic = B/Victoria. *B/Victoria assessed only in 2013–14 cohort (when it was a component of vaccine). A. Geometric mean titers (GMT) with 95% confidence intervals (CI). GMT for H3N2 and B Yam differed between PT and FT infants at Visit 5. **P<0.05. B. Fold change in titers between visits ± standard deviation (SD). v1 = Visit 1, v5 = Visit 5, v6 = Visit 6. Fold change in titers from Visits 1 to Visit 5 differed between PT and FT for H3N2 and B Yamagata and from Visits 5 and 6 for B/Yamagata and B/Victoria. **P<0.05.
Figure 2
Figure 2
Hemagglutination inhibition (HAI) titers. Serum was collected and analyzed at Visit 1 (0 days), Visit 5 (56 days) and Visit 6 (9 months). Pre-vaccine titers (Visit 1) were available for 7 preterm (PT) and all full-term (FT) infants and post-vaccine titers (Visits 5 and 6) available for all PT and 8 FT infants. B Yam = B/Yamagata. B Vic = B/Victoria. *B/Victoria assessed only in 2013–14 cohort (when it was a component of vaccine). A. Geometric mean titers (GMT) with 95% confidence intervals (CI). GMT for H3N2 and B Yam differed between PT and FT infants at Visit 5. **P<0.05. B. Fold change in titers between visits ± standard deviation (SD). v1 = Visit 1, v5 = Visit 5, v6 = Visit 6. Fold change in titers from Visits 1 to Visit 5 differed between PT and FT for H3N2 and B Yamagata and from Visits 5 and 6 for B/Yamagata and B/Victoria. **P<0.05.
Figure 3
Figure 3
Frequency of influenza antigen-specific antibody secreting cells (ASCs) measured by Enzyme-linked immunospot (ELISPOT) assay, as measured at Visits 2 (10 days) and 4 (35 days). A. Representative wells from preterm and full-term infants at each Visit. IgG = IgG-coated well, IV = influenza-vaccine-coated wells (TIV for 2012–13, QIV for 2013–14), Tet = tetanus-coated wells. B. Spots per million peripheral blood mononuclear cells (PBMC), normalized to bovine serum albumin (BSA) background at Visits 2 (V#2) and 4 (V#4). Preterm (PT) ASC numbers were higher than full-term (FT) numbers at Visit 4. Each square represents a separate child. Mean (central bar) and standard deviation (whiskers) are shown. Standard deviation extends below axis in some cases. *P = 0.04. C. Correlation between antigen-specific ASC frequency measured at Visit 4 and hemagglutination inhibition (HAI) titers measured at Visit 5 (56 days). ASC frequency and titer were modestly correlated for all serotypes. Each symbol represents a separate child (° = Preterm, + = Full-term). LOESS smoothing curves (loess) are shown to illustrate relationships. ρ = Spearman’s rho correlation coefficient.
Figure 3
Figure 3
Frequency of influenza antigen-specific antibody secreting cells (ASCs) measured by Enzyme-linked immunospot (ELISPOT) assay, as measured at Visits 2 (10 days) and 4 (35 days). A. Representative wells from preterm and full-term infants at each Visit. IgG = IgG-coated well, IV = influenza-vaccine-coated wells (TIV for 2012–13, QIV for 2013–14), Tet = tetanus-coated wells. B. Spots per million peripheral blood mononuclear cells (PBMC), normalized to bovine serum albumin (BSA) background at Visits 2 (V#2) and 4 (V#4). Preterm (PT) ASC numbers were higher than full-term (FT) numbers at Visit 4. Each square represents a separate child. Mean (central bar) and standard deviation (whiskers) are shown. Standard deviation extends below axis in some cases. *P = 0.04. C. Correlation between antigen-specific ASC frequency measured at Visit 4 and hemagglutination inhibition (HAI) titers measured at Visit 5 (56 days). ASC frequency and titer were modestly correlated for all serotypes. Each symbol represents a separate child (° = Preterm, + = Full-term). LOESS smoothing curves (loess) are shown to illustrate relationships. ρ = Spearman’s rho correlation coefficient.
Figure 3
Figure 3
Frequency of influenza antigen-specific antibody secreting cells (ASCs) measured by Enzyme-linked immunospot (ELISPOT) assay, as measured at Visits 2 (10 days) and 4 (35 days). A. Representative wells from preterm and full-term infants at each Visit. IgG = IgG-coated well, IV = influenza-vaccine-coated wells (TIV for 2012–13, QIV for 2013–14), Tet = tetanus-coated wells. B. Spots per million peripheral blood mononuclear cells (PBMC), normalized to bovine serum albumin (BSA) background at Visits 2 (V#2) and 4 (V#4). Preterm (PT) ASC numbers were higher than full-term (FT) numbers at Visit 4. Each square represents a separate child. Mean (central bar) and standard deviation (whiskers) are shown. Standard deviation extends below axis in some cases. *P = 0.04. C. Correlation between antigen-specific ASC frequency measured at Visit 4 and hemagglutination inhibition (HAI) titers measured at Visit 5 (56 days). ASC frequency and titer were modestly correlated for all serotypes. Each symbol represents a separate child (° = Preterm, + = Full-term). LOESS smoothing curves (loess) are shown to illustrate relationships. ρ = Spearman’s rho correlation coefficient.
Figure 4
Figure 4
ASC cell sub-populations, as measured by flow cytometry. A. Flow cytometry gating strategy. Cell populations 1–5 are described in Methods. B. Frequency of cell populations in preterm (PT) and full-term (FT) infants. Center bar represents mean and whiskers represent 95% confidence interval. Each symbol represents a separate child. There were no statistically significant differences in numbers of cells in any population per million peripheral blood mononuclear cells (PBMC) between FT and PT infants at any of the 3 visits (V). C. Correlation between frequency of CD19+ CD38hi CD138+ cells (Population 3) measured by flow cytometry at Visit 4 (35 days) and change in hemagglutination inhibition (HAI) titers measured at Visits 5 (56 days) and 6 (9 months). Each symbol represents a separate child (° = Preterm, + = Full-term). LOESS smoothing curves (loess) are shown to illustrate relationships. ρ = Spearman’s correlation coefficient. There were no statistically significant correlations between Population 3 frequency and HAI titer change for any strain.
Figure 4
Figure 4
ASC cell sub-populations, as measured by flow cytometry. A. Flow cytometry gating strategy. Cell populations 1–5 are described in Methods. B. Frequency of cell populations in preterm (PT) and full-term (FT) infants. Center bar represents mean and whiskers represent 95% confidence interval. Each symbol represents a separate child. There were no statistically significant differences in numbers of cells in any population per million peripheral blood mononuclear cells (PBMC) between FT and PT infants at any of the 3 visits (V). C. Correlation between frequency of CD19+ CD38hi CD138+ cells (Population 3) measured by flow cytometry at Visit 4 (35 days) and change in hemagglutination inhibition (HAI) titers measured at Visits 5 (56 days) and 6 (9 months). Each symbol represents a separate child (° = Preterm, + = Full-term). LOESS smoothing curves (loess) are shown to illustrate relationships. ρ = Spearman’s correlation coefficient. There were no statistically significant correlations between Population 3 frequency and HAI titer change for any strain.
Figure 4
Figure 4
ASC cell sub-populations, as measured by flow cytometry. A. Flow cytometry gating strategy. Cell populations 1–5 are described in Methods. B. Frequency of cell populations in preterm (PT) and full-term (FT) infants. Center bar represents mean and whiskers represent 95% confidence interval. Each symbol represents a separate child. There were no statistically significant differences in numbers of cells in any population per million peripheral blood mononuclear cells (PBMC) between FT and PT infants at any of the 3 visits (V). C. Correlation between frequency of CD19+ CD38hi CD138+ cells (Population 3) measured by flow cytometry at Visit 4 (35 days) and change in hemagglutination inhibition (HAI) titers measured at Visits 5 (56 days) and 6 (9 months). Each symbol represents a separate child (° = Preterm, + = Full-term). LOESS smoothing curves (loess) are shown to illustrate relationships. ρ = Spearman’s correlation coefficient. There were no statistically significant correlations between Population 3 frequency and HAI titer change for any strain.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Resch B, Kurath-Koller S, Eibisberger M, Zenz W. Prematurity and the burden of influenza and respiratory syncytial virus disease. World J Pediatr. 2016;12:8–18. - PubMed
    1. Sharma AA, Jen R, Butler A, Lavoie PM. The developing human preterm neonatal immune system: a case for more research in this area. Clin Immunol. 2012;145:61–8. - PMC - PubMed
    1. Washburn LK, O’Shea TM, Gillis DC, Block SM, Abramson JS. Response to Haemophilus influenzae type b conjugate vaccine in chronically ill premature infants. Journal of Pediatrics. 1993;123:791–4. - PubMed
    1. Greenberg DP, Vadheim CM, Partridge S, Chang SJ, Chiu CY, Ward JI. Immunogenicity of Haemophilus influenzae type b tetanus toxoid conjugate vaccine in young infants. The Kaiser-UCLA Vaccine Study Group. Journal of Infectious Diseases. 1994;170:76–81. - PubMed
    1. Munoz A, Salvador A, Brodsky NL, Arbeter AM, Porat R. Antibody response of low birth weight infants to Haemophilus influenzae type b polyribosylribitol phosphate-outer membrane protein conjugate vaccine. Pediatrics. 1995;96:216–9. - PubMed

Publication types

Substances