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

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 (≤32 weeks’ gestation, ≤1500 grams’ birth weight) and 11 FT infants, 6 to 17 months 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 28 days, and blood was drawn at 0, 10, 35, and 56 days and 9 months. Vaccine-specific antibody was measured by hemagglutination inhibition (HAI) at 0 and 56 days and 9 months, vaccine-specific ASC numbers by enzyme linked immunospot (ELISPOT) at 10 and 35 days, and ASC subsets by flow cytometry at 0, 10 and 35 days. Results PT infants had post-vaccine HAI titers to all 4 vaccine strains at least equal to FT infants at 56 days and 9 months after beginning immunization. Influenza-specific ASC ELISPOT responses at 35 days were higher among PT than FT infants (median 100 v. 30 per 106 PBMC, p = 0.04). ASC numbers at 35 days were positively correlated with serum HAI titers at 56 days (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. Conclusion(s) 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.

Differences in the influenza-specific CD4 T cell immunodominance hierarchy and functional potential between children and young adults

“…All children in our study had previously been vaccinated with IIV but had no history of previous natural influenza infection or LAIV administration, suggesting that early childhood IIV immunization is able to prime CD4 T cell reactivity but that the memory established remains more undifferentiated and mainly directed against the HA proteins predominant within IIV 27,28 . While it is well established that IIV primes B cells and is able to establish an antibody response in young children 29,30 , the priming of cellular immunity in children post-IIV administration has been more controversial. He et al .…”

Immunization of preterm infants: current evidence and future strategies to individualized approaches

“…B surface Ag Inact. Poliovirus Hib polysaccharide •CRI as a non-specific self-limiting stress reaction especially in most vulnerable infants [ 14 , 34 – 37 ] but no difference in CRI-rates in RCT between DTaP exposed and unexposed PIs [ 38 – 40 ] •post-immunization fever: 1.4%—33% [ 13 , 41 – 43 ] RCTs: [ 38 , 44 ] •excellent immunogenicity of most hexavalent components across all GA- and BW- groups [ 14 , 45 ] •inconclusive reports for pertussis and Hib vaccines [ 45 – 48 ] •Lower response of PIs to certain polio serotypes [ 14 , 49 - 51 ], Hib [ 52 – 54 ] and HBV [ 15 – 17 , 19 , 55 ] no RCTs •AAP/AGH/WHO/GOC: immunization of PIs according to chronological age without correction for prematurity •AGH: extra dose of Hib for ELGANs or VLBWI at 6 months of age depending on the vaccine used Pneumococcal vaccine (intramuscular) Conjugate vaccines (i.e., PCV13) Polysaccharide vaccines (i.e., PPSV23) •safe and well tolerated by PI [ 56 , 57 ] •comparable rate of AEs after immunization (compared to FTI) [ 58 , 59 ] •no serious, vaccine-related AEs reported RCTs: [ 56 ] •inconclusive results: GA-dependent specific IgG antibody titers [ 61 ] •reduced but protective responses to certain PCV serotypes [62,57,63,64 (importance of a booster dose [ 62 ]) •significant reduction in IPD in birth cohorts of PI [ 65 ] and up to 100% efficacy for PI and LBWI [ 59 , 60 ] RCTs: [ 56 ] •AGH/GOC: P...…”

Influenza in Children

“…IIV have been shown to be effective in both infants and young children (Jefferson et al 2018), with protective antibody levels and the generation of antibody-secreting cells in even former premature infants vaccinated at 6-17 mo of age (Groothuis et al 1992;D'Angio et al 2011D'Angio et al , 2017. This protection is predominately through stimulation of a HA-specific neutralizing antibody response quantified using the serum HAI antibody titer as a correlate of vaccine-induced protection.…”