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Thermostability of Well-Ordered HIV Spikes Correlates with the Elicitation of Autologous Tier 2 Neutralizing Antibodies
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نویسنده
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feng y. ,tran k. ,bale s. ,kumar s. ,guenaga j. ,wilson r. ,de val n. ,arendt h. ,destefano j. ,ward a.b. ,wyatt r.t.
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منبع
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plos pathogens - 2016 - دوره : 12 - شماره : 8
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چکیده
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In the context of hiv vaccine design and development,hiv-1 spike mimetics displaying a range of stabilities were evaluated to determine whether more stable,well-ordered trimers would more efficiently elicit neutralizing antibodies. to begin,in vitro analysis of trimers derived from the cysteine-stabilized sosip platform or the uncleaved,covalently linked nfl platform were evaluated. these native-like trimers,derived from hiv subtypes a,b,and c,displayed a range of thermostabilities,and were “stress-tested” at varying temperatures as a prelude to in vivo immunogenicity. analysis was performed both in the absence and in the presence of two different adjuvants. since partial trimer degradation was detected at 37°c before or after formulation with adjuvant,we sought to remedy such an undesirable outcome. cross-linking (fixing) of the well-ordered trimers with glutaraldehyde increased overall thermostability,maintenance of well-ordered trimer integrity without or with adjuvant,and increased resistance to solid phase-associated trimer unfolding. immunization of unfixed and fixed well-ordered trimers into animals revealed that the elicited tier 2 autologous neutralizing activity correlated with overall trimer thermostability,or melting temperature (tm). glutaraldehyde fixation also led to higher tier 2 autologous neutralization titers. these results link retention of trimer quaternary packing with elicitation of tier 2 autologous neutralizing activity,providing important insights for hiv-1 vaccine design. © 2016 feng et al.
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آدرس
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iavi neutralizing center at tsri,department of research and development,international aids vaccine initiative,la jolla,ca,united states,department of immunology and microbial science,the scripps research institute,la jolla,ca, United States, iavi neutralizing center at tsri,department of research and development,international aids vaccine initiative,la jolla,ca, United States, department of immunology and microbial science,the scripps research institute,la jolla,ca,united states,the scripps chavi-id,the scripps research institute,la jolla,ca, United States, iavi neutralizing center at tsri,department of research and development,international aids vaccine initiative,la jolla,ca, United States, iavi neutralizing center at tsri,department of research and development,international aids vaccine initiative,la jolla,ca, United States, iavi neutralizing center at tsri,department of research and development,international aids vaccine initiative,la jolla,ca, United States, department of integrative structural and computational biology,the scripps research institute,la jolla,ca, United States, iavi design and development lab,department of research and development,international aids vaccine initiative,brooklyn,ny, United States, iavi design and development lab,department of research and development,international aids vaccine initiative,brooklyn,ny, United States, iavi neutralizing center at tsri,department of research and development,international aids vaccine initiative,la jolla,ca,united states,the scripps chavi-id,the scripps research institute,la jolla,ca,united states,department of integrative structural and computational biology,the scripps research institute,la jolla,ca, United States, iavi neutralizing center at tsri,department of research and development,international aids vaccine initiative,la jolla,ca,united states,department of immunology and microbial science,the scripps research institute,la jolla,ca,united states,the scripps chavi-id,the scripps research institute,la jolla,ca, United States
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Authors
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