Enhanced HIV-1 immunotherapy by commonly arising antibodies that target virus escape variants

نویسندگان

  • Florian Klein
  • Lilian Nogueira
  • Yoshiaki Nishimura
  • Ganesh Phad
  • Anthony P. West
  • Ariel Halper-Stromberg
  • Joshua A. Horwitz
  • Anna Gazumyan
  • Cassie Liu
  • Thomas R. Eisenreich
  • Clara Lehmann
  • Gerd Fätkenheuer
  • Constance Williams
  • Masashi Shingai
  • Malcolm A. Martin
  • Pamela J. Bjorkman
  • Michael S. Seaman
  • Susan Zolla-Pazner
  • Gunilla B. Karlsson Hedestam
  • Michel C. Nussenzweig
چکیده

Antibody-mediated immunotherapy is effective in humanized mice when combinations of broadly neutralizing antibodies (bNAbs) are used that target nonoverlapping sites on the human immunodeficiency virus type 1 (HIV-1) envelope. In contrast, single bNAbs can control simian-human immunodeficiency virus (SHIV) infection in immune-competent macaques, suggesting that the host immune response might also contribute to the control of viremia. Here, we investigate how the autologous antibody response in intact hosts can contribute to the success of immunotherapy. We find that frequently arising antibodies that normally fail to control HIV-1 infection can synergize with passively administered bNAbs by preventing the emergence of bNAb viral escape variants.

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

Early Low-Titer Neutralizing Antibodies Impede HIV-1 Replication and Select for Virus Escape

Single genome sequencing of early HIV-1 genomes provides a sensitive, dynamic assessment of virus evolution and insight into the earliest anti-viral immune responses in vivo. By using this approach, together with deep sequencing, site-directed mutagenesis, antibody adsorptions and virus-entry assays, we found evidence in three subjects of neutralizing antibody (Nab) responses as early as 2 week...

متن کامل

Antibody-Based Strategies to Prevent and Treat Influenza

Passive immunization using antibodies is a promising alternative to other antiviral treatment options. The potential for seasonal protection arising from a single injection of antibodies is appealing and has been pursued for a number of infectious agents. However, until recently, antibody-based strategies to combat infectious agents have been hampered due to the fact that most antibodies have b...

متن کامل

Viral Escape from Neutralizing Antibodies in Early Subtype A HIV-1 Infection Drives an Increase in Autologous Neutralization Breadth

Antibodies that neutralize (nAbs) genetically diverse HIV-1 strains have been recovered from a subset of HIV-1 infected subjects during chronic infection. Exact mechanisms that expand the otherwise narrow neutralization capacity observed during early infection are, however, currently undefined. Here we characterized the earliest nAb responses in a subtype A HIV-1 infected Rwandan seroconverter ...

متن کامل

Neutralizing antibody escape during HIV-1 mother-to-child transmission involves conformational masking of distal epitopes in envelope.

HIV-1 variants transmitted to infants are often resistant to maternal neutralizing antibodies (NAbs), suggesting that they have escaped maternal NAb pressure. To define the molecular basis of NAb escape that contributes to selection of transmitted variants, we analyzed 5 viruses from 2 mother-to-child transmission pairs, in which the infant virus, but not the maternal virus, was resistant to ne...

متن کامل

The Cat and Mouse of HIV-1 Antibody Escape

Human immunodeficiency virus type 1 (HIV-1) is a chronically replicating lentivirus that must escape from adaptive immune responses that arise during the course of infection. Viral persistence is maintained by the rapid rate of HIV-1 replication and the error-prone reverse transcription of the viral genome, which produces viral variants that continually escape antibody and cytotoxic T cell resp...

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:

دوره 211  شماره 

صفحات  -

تاریخ انتشار 2014