HIV-1 VACCINES. HIV-1 neutralizing antibodies induced by native-like envelope trimers.

نویسندگان

  • Rogier W Sanders
  • Marit J van Gils
  • Ronald Derking
  • Devin Sok
  • Thomas J Ketas
  • Judith A Burger
  • Gabriel Ozorowski
  • Albert Cupo
  • Cassandra Simonich
  • Leslie Goo
  • Heather Arendt
  • Helen J Kim
  • Jeong Hyun Lee
  • Pavel Pugach
  • Melissa Williams
  • Gargi Debnath
  • Brian Moldt
  • Mariëlle J van Breemen
  • Gözde Isik
  • Max Medina-Ramírez
  • Jaap Willem Back
  • Wayne C Koff
  • Jean-Philippe Julien
  • Eva G Rakasz
  • Michael S Seaman
  • Miklos Guttman
  • Kelly K Lee
  • Per Johan Klasse
  • Celia LaBranche
  • William R Schief
  • Ian A Wilson
  • Julie Overbaugh
  • Dennis R Burton
  • Andrew B Ward
  • David C Montefiori
  • Hansi Dean
  • John P Moore
چکیده

A challenge for HIV-1 immunogen design is the difficulty of inducing neutralizing antibodies (NAbs) against neutralization-resistant (tier 2) viruses that dominate human transmissions. We show that a soluble recombinant HIV-1 envelope glycoprotein trimer that adopts a native conformation, BG505 SOSIP.664, induced NAbs potently against the sequence-matched tier 2 virus in rabbits and similar but weaker responses in macaques. The trimer also consistently induced cross-reactive NAbs against more sensitive (tier 1) viruses. Tier 2 NAbs recognized conformational epitopes that differed between animals and in some cases overlapped with those recognized by broadly neutralizing antibodies (bNAbs), whereas tier 1 responses targeted linear V3 epitopes. A second trimer, B41 SOSIP.664, also induced a strong autologous tier 2 NAb response in rabbits. Thus, native-like trimers represent a promising starting point for the development of HIV-1 vaccines aimed at inducing bNAbs.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Immunogenicity in Rabbits of HIV-1 SOSIP Trimers from Clades A, B, and C, Given Individually, Sequentially, or in Combination

Recombinant soluble HIV-1 envelope glycoprotein (Env) SOSIP trimers are a design platform for inducing broadly neutralizing antibodies (bNAbs) by vaccination. To date, these and alternative designs of native-like trimers, given singly or in pairs, have not induced bNAbs in test animals such as rabbits or macaques. Here, we have evaluated whether trivalent and tetravalent combinations of SOSIP t...

متن کامل

Characterization of a stable HIV-1 B/C recombinant, soluble, and trimeric envelope glycoprotein (Env) highly resistant to CD4-induced conformational changes

The HIV-1 envelope (Env) is a glycoprotein consisting of a trimer of heterodimers containing gp120 and gp41 subunits that mediates virus entry and is a major target of broadly neutralizing antibodies (bnAbs) developed during infection in some individuals. The engagement of the HIV-1 gp120 glycoprotein to the host CD4 protein triggers conformational changes in gp120 that allow its binding to co-...

متن کامل

Native‐like Env trimers as a platform for HIV‐1 vaccine design

We describe the development and potential use of various designs of recombinant HIV-1 envelope glycoprotein trimers that mimic the structure of the virion-associated spike, which is the target for neutralizing antibodies. The goal of trimer development programs is to induce broadly neutralizing antibodies with the potential to intervene against multiple circulating HIV-1 strains. Among the topi...

متن کامل

HIV-1 envelope trimer elicits more potent neutralizing antibody responses than monomeric gp120.

HIV-1 envelope glycoprotein is the primary target for HIV-1-specific antibodies. The native HIV-1 envelope spike on the virion surface is a trimer, but trimeric gp140 and monomeric gp120 currently are believed to induce comparable immune responses. Indeed, most studies on the immunogenicity of HIV-1 envelope oligomers have revealed only marginal improvement over monomers. We report here that su...

متن کامل

Improving the Immunogenicity of Native-like HIV-1 Envelope Trimers by Hyperstabilization.

The production of native-like recombinant versions of the HIV-1 envelope glycoprotein (Env) trimer requires overcoming the natural flexibility and instability of the complex. The engineered BG505 SOSIP.664 trimer mimics the structure and antigenicity of native Env. Here, we describe how the introduction of new disulfide bonds between the glycoprotein (gp)120 and gp41 subunits of SOSIP trimers o...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:
  • Science

دوره 349 6244  شماره 

صفحات  -

تاریخ انتشار 2015