UMMS Affiliation

Department of Medicine, Division of Infectious Diseases and Immunology

Publication Date

9-1-2013

Document Type

Article

Subjects

Animals; Antibodies, Monoclonal; Cross Reactions; Epitopes; HIV Antibodies; HIV Envelope Protein gp120; HIV-1; Neutralization Tests; Rabbits

Disciplines

Immunology of Infectious Disease | Immunoprophylaxis and Therapy | Infectious Disease | Virology | Virus Diseases

Abstract

The majority of available monoclonal antibodies (MAbs) in the current HIV vaccine field are generated from HIV-1-infected people. In contrast, preclinical immunogenicity studies have mainly focused on polyclonal antibody responses in experimental animals. Although rabbits have been widely used for antibody studies, there has been no report of using rabbit MAbs to dissect the specificity of antibody responses for AIDS vaccine development. Here we report on the production of a panel of 12 MAbs from a New Zealand White (NZW) rabbit that was immunized with an HIV-1 JR-FL gp120 DNA prime and protein boost vaccination regimen. These rabbit MAbs recognized a diverse repertoire of envelope (Env) epitopes ranging from the highly immunogenic V3 region to several previously underappreciated epitopes in the C1, C4, and C5 regions. Nine MAbs showed cross-reactivity to gp120s of clades other than clade B. Increased somatic mutation and extended CDR3 were observed with Ig genes of several molecularly cloned rabbit MAbs. Phylogenic tree analysis showed that the heavy chains of MAbs recognizing the same region on gp120 tend to segregate into an independent subtree. At least three rabbit MAbs showed neutralizing activities with various degrees of breadth and potency. The establishment of this rabbit MAb platform will significantly enhance our ability to test optimal designs of Env immunogens to gain a better understanding of the structural specificity and evolution process of Env-specific antibody responses elicited by candidate AIDS vaccines.

Rights and Permissions

Citation: J Virol. 2013 Sep;87(18):10232-43. doi: 10.1128/JVI.00837-13. Epub 2013 Jul 17. Link to article on publisher's site

DOI of Published Version

10.1128/JVI.00837-13

Related Resources

Link to Article in PubMed

Journal/Book/Conference Title

Journal of virology

PubMed ID

23864612

 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.