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Frey, Steven J.; Carreño, Juan Manuel; Bielak, Dominika; Arsiwala, Ammar; Altomare, Clara G.; Varner, Chad; Rosen‐Cheriyan, Tania; Bajic, Goran; Krammer, Florian; Kane, Ravi S.
Advanced healthcare materials, 05/2023, Letnik: 12, Številka: 13Journal Article
Despite the availability of licensed vaccines, influenza causes considerable morbidity and mortality worldwide. Current influenza vaccines elicit an immune response that primarily targets the head domain of the viral glycoprotein hemagglutinin (HA). Influenza viruses, however, readily evade this response by acquiring mutations in the head domain. While vaccines that target the more conserved HA stalk may circumvent this problem, low levels of antistalk antibodies are elicited by vaccination, possibly due to the poor accessibility of the stalk domain to B cell receptors. In this work, it is demonstrated that nanoparticles presenting HA in an inverted orientation generate tenfold higher antistalk antibody titers after a prime immunization and fivefold higher antistalk titers after a boost than nanoparticles displaying HA in its regular orientation. Moreover, nanoparticles presenting HA in an inverted orientation elicit a broader antistalk response that reduces mouse weight loss and improves survival after challenge to a greater extent than nanoparticles displaying HA in a regular orientation. Refocusing the antibody response toward conserved epitopes by controlling antigen orientation may enable the design of broadly protective nanovaccines targeting influenza viruses and other pathogens with pandemic potential. The immune system generally targets the variable head domain of the influenza protein hemagglutinin (HA) rather than its conserved stalk domain, which results in a strain‐specific response. This phenomenon may be a result of HA orientation. In this work, nanoparticles that display HA in an inverted orientation are developed and found to elicit an enhanced stalk‐directed antibody response.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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Vir: Osebne bibliografije
in: SICRIS
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