Fig. 1
Overview of multi-strain model. (A) Vaccine antigen uptake by antigen-presenting cells (APCs). (B) Once loaded, APCs migrate from the injection site to the lymph nodes. Antigens (HA, NA) can also reach the lymph nodes by passive lymphatic drainage. (C) Immunization in the lymph nodes results in a back-boost of prior immunity (historical strains, H) as well as the formation of new immunity specific to the vaccine strain (V). In the lymph nodes, several cell-cell interactions amplify the proliferation of specific immune cells, notably, the interaction between APCs and naïve B and CD4 + cells. Activated CD4 + cells also interact with B and CD8 + cells which differentiate into effector cells, with neutralizing and cytolytic functions respectively. (D) Upon exposure to a seasonal circulating strain (C), specific immune cells migrate from the lymph nodes to the lungs. The different populations of immune cells interact with the new antigen C according to a cross-reactivity curve relating binding avidity constants to AgD between the new antigens and the old ones that elicited each strain-specific population. The rates of neutralization of specific antibodies elicited against H and V respectively depend on the AgD in HA and NA between H and C and V and C, weighted by the relative abundance of HA (90%) and NA (10%). 60% of pre-existing CD8 + cells have a rate of cytolysis which is independent of the AgD in HA and NA between previously encountered antigens (H, V) and C. If the specific immunity raised against H and V strains is sufficient to suppress the replication of the circulating strain or to control it without symptoms, the infection is respectively considered prevented or sub-clinical. (E) In case of viral replication and appearance of symptoms corresponding to a vaccine breakthrough infection, there is an immunization against strain C, with a back-boost of the specific immunity against V and H. In case of severe infection lasting more than a few weeks, this new immunity against strain C can help resolve the infection.
