Pulendran and colleagues use a systems biology analysis to reveal distinct transcriptional signatures of antibody responses to different classes of human vaccines. Many vaccines induce protective immunity via antibodies. Systems biology approaches have been used to determine signatures that can be used to predict vaccine-induced immunity in humans, but whether there is a 'universal signature' that can be used to predict antibody responses to any vaccine is unknown. Here we did systems analyses of immune responses to the polysaccharide and conjugate vaccines against meningococcus in healthy adults, in the broader context of published studies of vaccines against yellow fever virus and influenza virus. To achieve this, we did a large-scale network integration of publicly available human blood transcriptomes and systems-scale databases in specific biological contexts and deduced a set of transcription modules in blood. Those modules revealed distinct transcriptional signatures of antibody responses to different classes of vaccines, which provided key insights into primary viral, protein recall and anti-polysaccharide responses. Our results elucidate the early transcriptional programs that orchestrate vaccine immunity in humans and demonstrate the power of integrative network modeling.

A boost for boosters: The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern poses a potential obstacle to achieving vaccine-induced immunity. Pegu et al . examined how viral variants, including the B.1.351 (Beta) and B.1.617.2 (Delta) variant, affected the immune response in a small number of individuals who received the Moderna mRNA-1273 vaccine. By analyzing sera obtained 6 months after the second shot in the primary vaccine series, the researchers found that neutralizing antibody titers persisted against all variants tested. However, neutralizing antibodies against the B1.351 variant had dropped considerably by 6 months, and some individuals had weak, and in some cases no, neutralizing activity. These data may help to guide public health policies regarding additional booster vaccinations. —PNK