In contrast, although they do not represent a correlate of protection, serum antibody levels following LAIV can be more consistently evaluated as the serum compartment is not subject to the same variability in content and sampling. For this reason, serum antibody responses following LAIV are the preferred method for evaluating the immunologic comparability of vaccine formulations signaling pathway or administration

schemes [13], [21], [45], [46], [47], [48] and [49]. In the current analysis, IgA and HAI responses were correlated, as IgA responses were more frequently observed among subjects with a HAI response. The primary limitation of the current analysis is the small size of the study cohorts. Although the pooled sample enabled an examination of the relationship between IgA and the incidence of influenza illness, the analysis would have benefited from larger cohort populations.

Averaging of IgA ratios across studies can also be problematic due to variability in values across types/subtypes and across studies. However, it is reassuring that the conclusions of the pooled analyses were supported by similar and consistent trends by study and type/subtype. In the analysis of the relationship between IgA and culture-confirmed influenza illness, it is possible that subjects without culture-confirmed influenza illness still experienced influenza infection; however, identification of these cases would likely have strengthened the Luminespib supplier observed relationship. Additionally, the assay was specific to IgA and did not evaluate nasal IgM or IgG antibody, which can also contribute to mucosal immunity [1]; a postvaccination increase in nasal enough wash IgG was observed in a prior study of LAIV [36]. In study 3, significant increases in total IgA were observed between baseline and postvaccination samples. Among prevaccination samples, which would not be subject to vaccine-induced effects, subjects who enrolled later had significantly higher total IgA, suggesting that

site sample collection technique improved over time. This observation supports the practice of providing interspecimen standardization by reporting IgA values as ratios of specific to total IgA. A postvaccination rise in total IgA has also been reported following intranasal measles vaccination; however, the study lacked a placebo control and thus it was not possible to determine whether the total IgA increase was vaccine-attributable [50]. In conclusion, results from 3 clinical studies in young children demonstrated that LAIV induced measurable strain-specific IgA after vaccination and that IgA responses are associated with protection from subsequent influenza illness. However, the inherent heterogeneity in nasal antibody levels and variability in nasal specimen collection hinders the precise evaluation of mucosal antibody responses, and measured IgA responses do not fully explain LAIV-induced protection. This study was sponsored by MedImmune, LLC.