Longitudinal and Integrative Biomodeling of Effector and Memory Immune Compartments after Inactivated Influenza Vaccination

Abstract

Most vaccines, including those against influenza, were developed by focusing solely on humoral response for protection. However, vaccination activates different adaptive compartments that might play a role in protection. We took advantage of the pandemic 2009 A(H1N1) influenza vaccination to conduct a longitudinal integrative multiparametric analysis of seven immune parameters in vaccinated subjects. A global analysis underlined the predominance of induction of humoral and CD4 T cell responses, whereas pandemic 2009 A(H1N1)–specific CD8 responses did not improve after vaccination. A principal component analysis and hierarchical clustering of individuals showed a differential upregulation of influenza vaccine–specific immunity including hemagglutination inhibition titers, IgA+ and IgG+ Ab-secreting cells, effector CD4 or CD8 T cell frequencies at day 21 among individuals, suggesting a fine-tuning of the immune parameters after vaccination. This is related to individual factors including the magnitude and quality of influenza-specific immune responses before vaccination. We propose a graphical delineation of immune determinants that would be essential for a better understanding of vaccine-induced immunity in vaccination strategies.

Characterization of pandemic influenza immune memory signature after vaccination or infection

“…We found that the higher the baseline (of preexisting flu-specific immune responses) was, the lower the amplification of responses was at 3 weeks after immunization (Δ between baseline and 3 weeks for effector immune responses). We did find significant differences in the intensity of the cellular and humoral responses at the memory phase (month 4) between the low-and high-baseline groups; this suggest that baseline immune responses affect the amplitude of immune memory (21).…”

“…Unfortunately, data on preexisting immune responses are not available in our study groups: what we have is a snapshot of the immune memory against influenza. We recently published an analysis of immune responses before and after vaccination at day 21 and at memory phase month 4 (21). We found that the higher the baseline (of preexisting flu-specific immune responses) was, the lower the amplification of responses was at 3 weeks after immunization (Δ between baseline and 3 weeks for effector immune responses).…”

“…It is not yet clear whether vaccination generates levels and characteristics of immune memory similar to those induced by infection itself, although adjuvants to vaccines are supposed to enhance both the signal strength and exposure duration. We recently proposed that the extreme heterogeneity of immune responses to influenza A(H1N1)pmd09 three weeks after vaccination is related to individual factors, including the magnitude and quality of influenza-specific immune responses before vaccination (21).…”

Key differences in B cell activation patterns and immune correlates among treated HIV-infected patients versus healthy controls following influenza vaccination

“…In HIV-infected patients, responses to influenza vaccination are frequently impaired [5,17-19]. CD4+ T cells, especially T follicular helper (Tfh) cells, B cells, innate immunity, sex, age, and the magnitude of viral replication have been shown to correlate with responses to influenza vaccination in HIV-infected patients [5,8,10,12-14,17,20-30]. In contrast, a study conducted by Siegrist et al has shown that HIV-infected patients have higher memory responses following pandemic influenza vaccination [31].…”

Booster influenza vaccination does not improve immune response in adult inflammatory bowel disease patients treated with immunosuppressives: a randomized controlled trial

“…or CD8 ? T cells specific to the conserved viral core protein epitopes correlated with the cross-reactive cellular immune responses, not the strain-matched B cell, which may make the development of a novel influenza vaccine possible [35,36].…”