Two closely related Env antigens from the same patient elicited different spectra of neutralizing antibodies against heterologous HIV-1 isolates
Authors
Vaine, MichaelDuenas-Decamp, Maria J.
Peters, Paul J.
Liu, Qin
Arthos, James
Wang, Shixia
Clapham, Paul R.
Lu, Shan
UMass Chan Affiliations
Program in Molecular Medicine, and Department of Molecular Genetics and MicrobiologyGraduate School of Biomedical Sciences
Department of Preventive and Behavioral Medicine
Department of Cancer Biology
Center for AIDS Research
Program in Immunology and Virology
Infectious Diseases and Immunology
Clinical and Population Health Research
Department of Medicine
Document Type
Journal ArticlePublication Date
2011-03-01Keywords
AnimalsAntibodies, Neutralizing
Brain
HIV Antibodies
HIV Infections
HIV-1
Humans
Immunization
Immunization, Secondary
Lymph Nodes
Rabbits
Viral Tropism
env Gene Products, Human Immunodeficiency Virus
dosage
Life Sciences
Medicine and Health Sciences
Women's Studies
Metadata
Show full item recordAbstract
Identification of immunogens capable of eliciting broadly neutralizing antibody (NAb) responses against HIV-1 is a major goal toward the development of an AIDS vaccine. Despite significant progress in understanding the structural features of the HIV-1 envelope glycoprotein (Env) and the discovery of multiple broadly neutralizing monoclonal antibodies with defined antigenic structures, the design of optimal Env immunogens to elicit broad NAbs remains a major challenge. As the structural determinants of Env immunogenicity remain unclear, we assessed two closely related Env antigens isolated from the same HIV-1-infected patient with different phenotypic features to identify what may result in a favorable immunogenic profile. One Env, B33, isolated from brain, was highly macrophage tropic with a high CD4 affinity, while the other, LN40, isolated from the lymph nodes, was poorly macrophage tropic with a low CD4 affinity. Using a DNA prime-protein boost approach, rabbits primed with LN40 Env antigen had a NAb response against heterologous primary isolates, while B33 Env antigens were capable of eliciting NAbs against only homologous and sensitive viral isolates. Further analysis revealed that the specificity of NAbs elicited by the LN40 antigen mapped to limited residues within or flanking the CD4 binding site. Certain key structural determinants were identified that could differentiate primary Env immunogens based on their potential to elicit broader NAbs. This progress will facilitate the rational design of effective HIV-1 vaccine formulations with optimal Env antigens.Source
J Virol. 2011 May;85(10):4927-36. Epub 2011 Mar 16. Link to article on publisher's site
DOI
10.1128/JVI.00081-11Permanent Link to this Item
http://hdl.handle.net/20.500.14038/50991PubMed ID
21411542Related Resources
ae974a485f413a2113503eed53cd6c53
10.1128/JVI.00081-11