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-Structure paper
タイトル | Induction of tier-2 neutralizing antibodies in mice with a DNA-encoded HIV envelope native like trimer. |
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ジャーナル・号・ページ | Nat Commun, Vol. 13, Issue 1, Page 695, Year 2022 |
掲載日 | 2022年2月4日 |
著者 | Ziyang Xu / Susanne Walker / Megan C Wise / Neethu Chokkalingam / Mansi Purwar / Alan Moore / Edgar Tello-Ruiz / Yuanhan Wu / Sonali Majumdar / Kylie M Konrath / Abhijeet Kulkarni / Nicholas J Tursi / Faraz I Zaidi / Emma L Reuschel / Ishaan Patel / April Obeirne / Jianqiu Du / Katherine Schultheis / Lauren Gites / Trevor Smith / Janess Mendoza / Kate E Broderick / Laurent Humeau / Jesper Pallesen / David B Weiner / Daniel W Kulp / |
PubMed 要旨 | HIV Envelope (Env) is the main vaccine target for induction of neutralizing antibodies. Stabilizing Env into native-like trimer (NLT) conformations is required for recombinant protein immunogens to ...HIV Envelope (Env) is the main vaccine target for induction of neutralizing antibodies. Stabilizing Env into native-like trimer (NLT) conformations is required for recombinant protein immunogens to induce autologous neutralizing antibodies(nAbs) against difficult to neutralize HIV strains (tier-2) in rabbits and non-human primates. Immunizations of mice with NLTs have generally failed to induce tier-2 nAbs. Here, we show that DNA-encoded NLTs fold properly in vivo and induce autologous tier-2 nAbs in mice. DNA-encoded NLTs also uniquely induce both CD4 + and CD8 + T-cell responses as compared to corresponding protein immunizations. Murine neutralizing antibodies are identified with an advanced sequencing technology. The structure of an Env-Ab (C05) complex, as determined by cryo-EM, identifies a previously undescribed neutralizing Env C3/V5 epitope. Beyond potential functional immunity gains, DNA vaccines permit in vivo folding of structured antigens and provide significant cost and speed advantages for enabling rapid evaluation of new HIV vaccines. |
リンク | Nat Commun / PubMed:35121758 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.8 Å |
構造データ | EMDB-25376, PDB-7sq1: |
化合物 | ChemComp-NAG: |
由来 |
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キーワード | Viral Protein/Immune System / antibody / Env / envelope / Viral Protein-Immune System complex |