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                <forename type="first">Fabian</forename>
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            <funder>FS was supported by the Swiss initiative for systems biology (SystemsX.ch). BEC was supported by the European Research Council (Starting grant - 716058) and the Swiss National Science Foundation (Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung; 310030_163139).</funder>
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            <idno type="stamp" n="INSERM">INSERM - Institut national de la santé et de la recherche médicale</idno>
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            <idno type="stamp" n="UNIV-PARIS-SACLAY">Université Paris-Saclay</idno>
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            <idno type="stamp" n="INRAE">Institut National de Recherche en Agriculture, Alimentation et Environnement</idno>
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                <title level="j">PLoS Biology</title>
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                  <biblScope unit="volume">17</biblScope>
                  <biblScope unit="issue">2</biblScope>
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                <term xml:lang="en">hiv</term>
                <term xml:lang="en">rsv antibody</term>
                <term xml:lang="en">hemagglutinin-stem</term>
                <term xml:lang="en">dependent enhancement</term>
                <term xml:lang="en">structural basis</term>
                <term xml:lang="en">respiratory syncytial virus</term>
                <term xml:lang="fr">infection</term>
                <term xml:lang="fr">cells</term>
                <term xml:lang="fr">dengue virus</term>
                <term xml:lang="fr">fusion-glycoprotein vaccine</term>
                <term xml:lang="fr">infection</term>
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              <p>Throughout the last several decades, vaccination has been key to prevent and eradicate infectious diseases. However, many pathogens (e.g., respiratory syncytial virus [RSV], influenza, dengue, and others) have resisted vaccine development efforts, largely because of the failure to induce potent antibody responses targeting conserved epitopes. Deep profiling of human B cells often reveals potent neutralizing antibodies that emerge from natural infection, but these specificities are generally subdominant (i.e., are present in low titers). A major challenge for next-generation vaccines is to overcome established immunodominance hierarchies and focus antibody responses on crucial neutralization epitopes. Here, we show that a computationally designed epitope-focused immunogen presenting a single RSV neutralization epitope elicits superior epitope-specific responses compared to the viral fusion protein. In addition, the epitope-focused immunogen efficiently boosts antibodies targeting the palivizumab epitope, resulting in enhanced neutralization. Overall, we show that epitope-focused immunogens can boost subdominant neutralizing antibody responses in vivo and reshape established antibody hierarchies.</p>
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