Viral Replicative Capacity, Antigen Availability via Hematogenous Spread, and High T FH :T FR Ratios Drive Induction of Potent Neutralizing Antibody Responses

Abstract

Neutralizing antibody response is the best-known correlate of long-term protective immunity for most of the currently licensed clinically effective viral vaccines. However, the host immune and viral factors that are critical for the induction of robust and durable antiviral humoral immune responses are not well understood. Our study provides insight into the dynamics of key cellular mediators of germinal center reaction during live virus infections and the influence of viral replicative capacity on the magnitude of antiviral antibody response and effector function. The significance of our study lies in two key findings. First, the systemic spread of even poorly replicating or nonreplicating viruses to mimic the spread of antigens from replicating viruses due to escalating antigen concentration is fundamental to the induction of durable antibody responses. Second, the T FH :T FR ratio may be used as an early predictor of protective antiviral humoral immune responses long before memory responses are generated.