Preexisting memory CD4 T cells in naïve individuals confer robust immunity upon hepatitis B vaccination

Abstract

Antigen recognition through the T cell receptor (TCR) αβ heterodimer is one of the primary determinants of the adaptive immune response. Vaccines activate naïve T cells with high specificity to expand and differentiate into memory T cells. However, antigen-specific memory CD4 T cells exist in unexposed antigen-naïve hosts. In this study, we use high-throughput sequencing of memory CD4 TCRβ repertoire and machine learning to show that individuals with preexisting vaccine-reactive memory CD4 T cell clonotypes elicited earlier and higher antibody titers and mounted a more robust CD4 T cell response to hepatitis B vaccine. In addition, integration of TCRβ sequence patterns into a hepatitis B epitope-specific annotation model can predict which individuals will have an early and more vigorous vaccine-elicited immunity. Thus, the presence of preexisting memory T cell clonotypes has a significant impact on immunity and can be used to predict immune responses to vaccination.

Multi-view learning to unravel the different levels underlying hepatitis B vaccine response

“…We implemented this multi-view analysis in this setting as to aid in finding interpretable patterns in a vaccination context, which has not been previously interrogated together. This study bases itself on the notion that prior studies have also highlighted correlations between the different levels and the eventual HBV response, as measured by the anti-HBs titers [19], [24], [40], [41]. To point out the most meaningful approach and improvement of predictive power of multi-view datasets, we used several integration methods.…”

“…The features included age, gender, temperature, maximum and minimum blood pressure (Min and Max_BP). Other clinical factors available included access to the absolute numbers of white blood cells (with differentiation in monocytes, lymphocytes and granulocytes), red blood cells (with separate attributes for hemoglobins and hematocrit) and platelets were determined with a haematology analyzer [19], [24] ( Supplemental material S1 ). Lastly, flow cytometry identified the percentages of CD4+ T cell relevant information ( Supplemental material S1 ), as this population is critical to developing a robust HBV antibody response.…”

“…The study participants had been previously recruited to assess the HBV vaccination response [19], [24]. The cohort consisted of HBV-naïve 34 individuals, who were neither vaccinated nor infected (according to serology) against/by HBV.…”

Leveraging T-cell receptor – epitope recognition models to disentangle unique and cross-reactive T-cell response to SARS-CoV-2 during COVID-19 progression/resolution

“…This explanation falls in line with previous reports where T cells recognizing SARS-CoV and seasonal coronaviruses were found to be crossreactive to SARS-CoV-2 (Braun et al, 2020; Lineburg et al, 2021; Mateus et al, 2020; Nesterenko et al, 2021). Alternatively, individuals may have had previously developed crossreactive CoV-common CD4+ T cells that might have facilitated more rapid CD8+ T cell development at the beginning of the SARS-CoV-2 infection, as has been recently demonstrated to be the case for antibody response to vaccination (Elias et al, 2022).…”

Pre-existing Immunity to Endemic Human Coronaviruses Does Not Affect the Immune Response to SARS-CoV-2 Spike in a Murine Vaccination Model

“…Cross-reactive immunological memory is an important consideration in vaccine development because it can have both beneficial and detrimental effects on the immune response elicited by vaccination. For instance, pre-existing immunity can be recalled for expansion, boosting the cross-reactive vaccine-induced immune response ( 11 12 ). Conversely, secondary expansion of pre-existing memory can limit the magnitude and diversity of the primary immune response to a cross-reactive yet distinct vaccine Ag.…”