Human Immunodeficiency Virus type 1 elite neutralizers:
Date
2009Author
Simek, Melissa D.
Rida, Wasima
Priddy, Frances H.
Pung, Pham
Carrow, Emily
Laufer, Dagna S.
Lehrman, Jennifer K.
Boaz, Mark
Tarragona-Fiol, Tony
Miiro, George
Birungi, Josephine
Pozniak, Anton
McPhee, Dale A.
Manigart, Olivier
Karita, Etienne
Inwoley, Andre´
Jaoko Walter G.
DeHovitz, Jack
Bekker, Linda-Gail
Pitisuttithum, Punnee
Paris, Robert
Walker, Laura M.
Poignard, Pascal
Wrin, Terri
Fast, Patricia E.
Burton, Dennis R.
Koff, Wayne C.
Type
ArticleLanguage
enMetadata
Show full item recordAbstract
The development of a rapid and efficient system to identify human immunodeficiency virus type 1 (HIV-1)-
infected individuals with broad and potent HIV-1-specific neutralizing antibody responses is an important step
toward the discovery of critical neutralization targets for rational AIDS vaccine design. In this study, samples
from HIV-1-infected volunteers from diverse epidemiological regions were screened for neutralization responses
using pseudovirus panels composed of clades A, B, C, and D and circulating recombinant forms
(CRFs). Initially, 463 serum and plasma samples from Australia, Rwanda, Uganda, the United Kingdom, and
Zambia were screened to explore neutralization patterns and selection ranking algorithms. Samples were
identified that neutralized representative isolates from at least four clade/CRF groups with titers above
prespecified thresholds and ranked based on a weighted average of their log-transformed neutralization titers.
Linear regression methods selected a five-pseudovirus subset, representing clades A, B, and C and one
CRF01_AE, that could identify top-ranking samples with 50% inhibitory concentration (IC50) neutralization
titers of >100 to multiple isolates within at least four clade groups. This reduced panel was then used to screen
1,234 new samples from the Ivory Coast, Kenya, South Africa, Thailand, and the United States, and 1% were
identified as elite neutralizers. Elite activity is defined as the ability to neutralize, on average, more than one
pseudovirus at an IC50 titer of 300 within a clade group and across at least four clade groups. These elite
neutralizers provide promising starting material for the isolation of broadly neutralizing monoclonal antibodies
to assist in HIV-1 vaccine design
URI
http://erepository.uonbi.ac.ke:8080/xmlui/handle/123456789/10151http://www.ncbi.nlm.nih.gov/pubmed/19439467
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2704778/
Citation
JOURNAL OF VIROLOGY, July 2009,Collections
- Faculty of Health Sciences (FHS) [10377]