Research ArticleINFECTIOUS DISEASE

Rapid profiling of RSV antibody repertoires from the memory B cells of naturally infected adult donors

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Science Immunology  09 Dec 2016:
Vol. 1, Issue 6, eaaj1879
DOI: 10.1126/sciimmunol.aaj1879

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RSV antibodies in profile

Respiratory syncytial virus (RSV) causes cold-like symptoms in healthy adults but can have serious complications in both the very young and elderly. No vaccine is approved for RSV, and although a prophylactic antibody, palivizumab, is available for high-risk infants, therapy is generally supportive. Now, Gilman et al. profile the human antibody response to the RSV fusion (F) glycoprotein. They find that the response is broad but that more potent antibodies tend to target the apex of the prefusion conformation of RSV F, suggesting this site as a putative vaccine target. Moreover, many of these antibodies were more potent than palivizumab and some cross-neutralized human metapneumovirus, making them candidates for new passive prophylactics.

Abstract

Respiratory syncytial virus (RSV) causes substantial morbidity and mortality in young children and the elderly. There are currently no licensed RSV vaccines, and passive prophylaxis with the monoclonal antibody palivizumab is restricted to high-risk infants in part due to its modest efficacy. Although it is widely agreed that an effective RSV vaccine will require the induction of a potent neutralizing antibody response against the RSV fusion (F) glycoprotein, little is known about the specificities and functional activities of RSV F–specific antibodies induced by natural infection. We have comprehensively profiled the human antibody response to RSV F by isolating and characterizing 364 RSV F–specific monoclonal antibodies from the memory B cells of three healthy adult donors. In all donors, the antibody response to RSV F was composed of a broad diversity of clones that targeted several antigenic sites. Nearly half of the most potent antibodies targeted a previously undefined site of vulnerability near the apex of the prefusion conformation of RSV F (preF). Additionally, the antibodies targeting this new site displayed convergent sequence features, thus providing a future means to rapidly detect the presence of these antibodies in human vaccine samples. Many of the antibodies that bind preF-specific surfaces were >100 times more potent than palivizumab and several cross-neutralized human metapneumovirus. Together, the results have implications for the design and evaluation of RSV vaccine candidates and offer new options for passive prophylaxis.

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