Vaccine-induced protection relies on the rapid and magnified immune memory recall responses induced following pathogen exposure. With mounting evidence that pathogens manipulate host immunity, the quality of the vaccine-induced immune memory becomes important when considering protection induced by vaccines. In this context, the quality of vaccine-induced immune memory can be seen as the ability of the immune response to resist manipulation by immuno-modulatory pathogens; we have termed this characteristic “immune memory resilience”.
In order to measure immune memory resilience we used sheep pre-femoral efferent lymphatic duct cannulation model. Taking advantage of the fact that immune responses could be studied in real time as they occur at the level of the lymph node and lymph recirculation is interrupted, we compared two adjuvants (alum and Quil A) in the same animal. Switching adjuvants for the booster allowed us to assess the resilience of the induced immune memory response. While both sides of the animal received the same total treatment, the sequence of adjuvants used was reversed. If the immune memory induced is resilient the sequence would matter and each side would be different following this treatment. However, without immune memory resilience, the outcome would be essentially the same.
Following a single vaccination with the model antigen, ovalbumin, and one adjuvant (OVA+ alum or OVA+ Quil A) the induced memory response was not resilient and was readily manipulated by the opposite adjuvant as measured by antibody isotype concentration (IgG2 for Th1 and IgG1 for Th2) and cytokine expression (IFN-ɣ for Th1 and IL-4 for Th2). Importantly, however, two vaccinations with the same adjuvant dramatically increased the level of resilience (i.e. quality) of the immune memory, in vivo, upon opposite adjuvant challenge. Thus vaccines against immunomodulatory pathogens would likely benefit from multiple injections.