Research ArticleVACCINES

Prolonged evolution of the memory B cell response induced by a replicating adenovirus-influenza H5 vaccine

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Science Immunology  19 Apr 2019:
Vol. 4, Issue 34, eaau2710
DOI: 10.1126/sciimmunol.aau2710

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Prolonged B cell responses

Replicating viral vaccines are known to induce durable and protective B cell responses, but previous studies have suggested that these responses may only evolve during active viral replication. Here, Matsuda et al. characterize memory B cell responses after vaccination with a replication-competent adenovirus-based influenza H5 recombinant vaccine over several months. Unexpectedly, they observed changes in B cell specificity and antibody affinity at 6 to 12 months after vaccination, long after viral replication ended. They detected antibodies with broad specificity, including a stem-specific antibody that shared similarities with another recently described antibody, thus defining a new multidonor class. These findings indicated that the B cell responses can evolve long after a single vaccination and provide insight into optimizing vaccine schedules.

Abstract

Induction of an antibody response capable of recognizing highly diverse strains is a major obstacle to the development of vaccines for viruses such as HIV and influenza. Here, we report the dynamics of B cell expansion and evolution at the single-cell level after vaccination with a replication-competent adenovirus type 4 recombinant virus expressing influenza H5 hemagglutinin. Fluorescent H1 or H5 probes were used to quantitate and isolate peripheral blood B cells and their antigen receptors. We observed increases in H5-specific antibody somatic hypermutation and potency for several months beyond the period of active viral replication that was not detectable at the serum level. Individual broad and potent antibodies could be isolated, including one stem-specific antibody that is part of a new multidonor class. These results demonstrate prolonged evolution of the B cell response for months after vaccination and should be considered in efforts to evaluate or boost vaccine-induced immunity.

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