Does live-attenuated vaccines trigger different host responses compared to inactivated vaccines? In this study, Nakaya et al., compared the transcriptomic responses of the influenza live-attenuated vaccine (LAIV) against the inactivated vaccine (TIV). Interestingly, despite both vaccines exhibiting similar clinical efficacy, the host responses that are induced by LAIV and TIV are vastly different. The summary of their findings are as follows:
Antibody responses of 56 healthy young adults vaccinated with either LAIV (n = 28) or TIV (n = 28).
Despite similar efficacy between the two vaccines, mean neutralising antibody response of subjects vaccinated with TIV was 6-fold higher than that of those vaccinated with LAIV. Of note, the magnitude of the antibody response can differ by >100-fold between subjects.
Only modest positive correlation was seen with IgG-secreting plasmablasts (day 7) and the HAI response (day 28). Among the different cytokines detected by the Luminex, only CXCL10 was significantly induced by TIV. However, CXCL10 does not correlate with neutralising antibody responses.
Interferon-related genes were induced by LAIV but not TIV. The transcriptomic data demonstrated that vaccination with TIV or LAIV induced distinct molecular signatures in the blood. The LAIV induce more genes related to T-cells whereas the TIV trigger more genes related to B-cells (see figure at top)
Correlation analysis reveal that XBP-1 related genes (Unfolded Protein Response), innate immune genes and reactive oxygen species response in macrophages were positively correlated with neutralising antibody responses. Interestingly, five members of the leukocyte immunoglobulin-like receptor family (LILRB1, LILRB2, LILRA1, LILRA3, LILRA6) were also correlated with neutralising antibody responses.
Based on their predictive network, the authors validated in mice that CAMPK4 is responsible for vaccine immunogenicity .
Data deposited as GSE29619.