Minimal determinants for lifelong antiviral antibody responses from a single exposure to virus-like immunogens at low doses

Abstract

AbstractThe durability of an antibody (Ab) response is highly important for antiviral vaccines. However, due to the complex compositions of natural virions, the molecular determinants of Ab durability from viral infection or inactivated viral vaccines have been incompletely understood. Here we used a reductionist system of liposome-based virus-like structures to examine the durability of Abs in primary immune responses. This system allowed us to independently vary fundamental viral attributes and to do so without additional adjuvants to model natural viruses. We show that a single injection of antigens (Ags) orderly displayed on a virion-sized liposome is sufficient to induce a long-lived neutralizing Ab (nAb) response. Introduction of internal nucleic acids dramatically modulates the magnitude of long-term Ab responses without alteration of the long-term kinetic trend. These Abs are characterized by exceptionally slow off-rates of ∼0.0005 s-1, which emerged as early as day 5 after injection and these off-rates are comparable to that of affinity-matured monoclonal Abs. A single injection of these structures at doses as low as 100 ng led to lifelong nAb production in BALB/c mice. Thus, we have defined the minimal determinants in virus-like immunogens that give rise to potent and long-lasting antiviral Abs from a primary encounter with the host without live infection. This has broad implications for understanding both live viral infection and for optimized vaccine design.One-sentence summaryReconstitution of minimal viral components necessary to trigger durable antiviral IgG