Correlates of Immunity to Influenza as Determined by Challenge of Children with Live, Attenuated Influenza Vaccine

Abstract

Background. The efficacy of live, attenuated live attenuated influenza vaccine(LAIV) and inactivated influenza vaccine(IIV) is poorly explained by either single or composite immune responses to vaccination. Protective biomarkers were therefore studied in response to LAIV or IIV followed by LAIV challenge in children.Methods. Serum and mucosal responses to LAIV or IIV were analyzed using immunologic assays to assess both quantitative and functional responses. Cytokines and chemokines were measured in nasal washes collected before vaccination, on days 2, 4, and 7 after initial LAIV, and again after LAIV challenge using a 63-multiplex Luminex panel.Results. Patterns of immunity induced by LAIV and IIV were significantly different. Serum responses induced by IIV, including hemagglutination inhibition, did not correlate with detection or quantitation of LAIV on subsequent challenge. Modalities that induced sterilizing immunity seen after LAIV challenge could not be defined by any measurements of mucosal or serum antibodies induced by the initial LAIV immunization. No single cytokine or chemokine was predictive of protection.Conclusions. The mechanism of protective immunity observed after LAIV could not be defined, and traditional measurements of immunity to IIV did not correlate with protection against an LAIV challenge.

Efficacy of a Russian-backbone live attenuated influenza vaccine among children in Senegal: a randomised, double-blind, placebo-controlled trial

“…One study described cell-mediated immunity as determined by ELISPOT assays that measure γ interferon as correlating with protection following live attenuated influenza vaccine in children; however, the results have not been corroborated and this measurement is difficult in remote field settings and among children 23 . A recent study of children aged 2–9 years further highlights the difficulty in identifying the immunological basis for protection by live attenuated influenza vaccine; 24 the study could not identify such a mechanism in a live attenuated influenza vaccine challenge model. Regardless, had we done mucosal or serum immunologic assays, we might at least have been able to confirm that vaccinees were responding immunologically in some way to live attenuated influenza vaccine.…”

Influenza in Children

“…In contrast to IIV, the correlates of LAIVinduced immunological protection remain unclear, with traditional measurements of immunity failing to correlate with protection from subsequent LAIV challenge (Wright et al 2016). Studies have established that the systemic neutralizing antibody titer is generally lower following immunization with LAIV as opposed to IIV (Treanor et al 1999;Sasaki et al 2007;Nakaya et al 2011;Ohmit et al 2011;Cao et al 2014), with higher LAIV-induced HAI titers associated with younger age and baseline seronegativity (Coelingh et al 2014).…”

Intestinal antibody responses to a live oral poliovirus vaccine challenge among adults previously immunized with inactivated polio vaccine in Sweden

“…Mucosal immunity to RSV and influenza has been demonstrated in the setting of natural infection and in response to immunisation with live and inactivated vaccines 34–37. Neutralisation of these viruses has been assessed in the past using mucosal specimens, including nasal washes, collected from the upper respiratory tract.…”