Seasonal Influenza Vaccination of Children Induces Humoral and Cell-Mediated Immunity Beyond the Current Season: Cross-reactivity With Past and Future Strains

Abstract

Background Influenza viruses gradually accumulate point mutations, reducing the effectiveness of prior immune protection. Methods Children aged 9–14 years received 2010–2011 trivalent inactivated influenza vaccine (TIV). Vaccination history, hemagglutination-inhibition (HI) titers, and cell-mediated immune responses were assessed to investigate the cross-reactivity with past and future influenza virus strains. Results 2010–2011 TIV induced significant T-cell responses and HI titers of ≥160, with a fold-rise of ≥4 and titers of ≥100 maintained for >7 months in the majority of children. Pre-existing memory B cells in these children differentiated quickly to antibody-secreting cells to the new vaccine antigens. Children vaccinated in the previous year maintained high HI titers well into 2010, demonstrating elevated HI titers against A/Perth/16/2009, the future (in 2010–2011) H3N2 component. Prior vaccination enhanced CD8+ T-cell responses to A/Perth/16/2009. Children vaccinated with the prior 2009–2010 seasonal vaccine also demonstrated higher preexisting levels of interferon γ–secreting CD4+CD69+ T cells to 2009 pandemic influenza A(H1N1). Children previously vaccinated with 2009–2010 seasonal influenza vaccine also showed greater expansion of tumor necrosis factor α–secreting CD8+CD69+ T cells to 2009 pandemic influenza A(H1N1) upon vaccination in the 2010–2011 season than those who were not previously vaccinated. Conclusions Seasonal influenza viruses continuously drift, which allows them to circumvent protective immunity, but conserved epitopes provide immunological cross-reactivity in children through either vaccination directly or through prime/boost in the prior influenza season.

Effectiveness of influenza vaccination on influenza-associated hospitalisations over time among children in Hong Kong: a test-negative case-control study

“…43 One established mechanism is that vaccine-induced antibody titers also decline over time. 9,10,44 This has been observed in children in Hong Kong and the United States, where vaccine-induced antibody titers measured by the hemagglutination inhibition assay waned by around half between 30 days and 6 months after vaccination. 9,10 However, antibody titers measured by the hemagglutination inhibition assay may not be perfect correlates of vaccine protection, and it is unclear whether a decline in antibody titers of this magnitude would lead to substantial differences in VE.…”

“…Annual revaccination is recommended for influenza because circulating influenza viruses continue to change antigenically, and usually at least one vaccine strain is changed each year. 7 In addition, some studies have reported reductions in antibody titers from 1 month to 6 months after vaccination, 8–10 and other studies have reported reductions in vaccination effectiveness (VE) with increasing time since vaccination. 11–15…”

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

“…Post-vaccination boosting of influenza-specific CD4 T cells was also reported by Reber et al . in a study of older children 32 . However, other groups have reported little priming of CD4 T cells following prime-boost administration of IIV in childhood 33,34 .…”

Influenza in Children

“…Although the preferential boosting of antibodies specific for earlier viral strains on encounter with an antigenically drifted influenza virus, or "original antigenic sin," was first described decades ago (Davenport et al 1953;Francis 1960;Fazekas de St.Groth and Webster 1966), recent data has indicated that influenza strains originally encountered in childhood may establish long lasting protection against novel influenza strains belonging to the same HA group (Gostic et al 2016). This cross-subtype protection has been termed "immunologic imprinting," and there is now an appreciation for its role in both establishing lasting anti-influenza protective immunity and in shaping lifelong responses to influenza vaccination (Reber et al 2016;Nachbagauer et al 2017;Nuñez et al 2017;Kosikova et al 2018).…”