Standardized Assessments of Neutralizing Antibodies for HIV/AIDS
Vaccine Development
David C. Montefiori, Duke University Medical Center
Introduction
This site provides detailed information for making standardized
assessments of neutralizing antibodies against HIV, SIV and SHIV using
molecularly cloned Env-pseudotyped viruses in an optimized and
validated luciferase (Luc) reporter gene assay. Access is provided to
assay protocols and macros currently in use at the Duke Central
Reference Laboratory. This site also contains educational slides,
tutorials and links to relevant publications and assay reagents.
Special attention is given to HIV-1 reference strains that are
available as molecularly cloned Env-pseudotyped viruses.
Assay Protocol and Support Documents:
Key Publications:
-
Mascola et al. 2005. Recommendations for the Design and Use of
Standard Virus Panels To Assess Neutralizing Antibody Responses
Elicited by Candidate Human Immunodeficiency Virus Type 1
Vaccines. J Virol. 2005 Aug;79(16):10103-7.
PMID
16051803
-
Li et al. 2005. Human Immunodeficiency Virus Type 1 env Clones
from Acute and Early Subtype B Infections for Standardized
Assessments of Vaccine-Elicited Neutralizing Antibodies. J
Virol. Aug;79(16):10108-25.
PMID
16051804
-
Li et al. 2006. Genetic and Neutralization Properties of Subtype
C Human Immunodeficiency Virus Type 1 Molecular env Clones from
Acute and early Heterosexually Acquired Infections in Southern
Africa.
PMID
16971434. (Link to PDF.)
-
Kulkarni et al. 2009. Highly Complex Neutralization Determinants
on a Monophyletic Lineage of Newly Transmitted Subtype C HIV-1
Env Clones from India. Virol., 385(2):
505-20. PMID:
19167740
-
Gnanakaran et al. 2010. Genetic Signatures in the Envelope
Glycoproteins of HIV-1 that Associate with Broadly Neutralizing
Antibodies. PLoS Comput. Biol., 6(10):
E1000955. PMID:
20949103
-
Seaman et al. 2010. Tiered Categorization of a Diverse Panel of
HIV-1 Env Pseudoviruses for Assessment of Neutralizing
Antibodies.
PMID
19939925. (Link
to PDF.)
-
Ozaki et al. 2012. International technology transfer of a
GCLP-compliant HIV-1 neutralizing antibody assay for human
clinical trials. PLoS One, 7(1):
e30963. PMID:
22303476
-
Todd et al. 2012. Development of implementation of an
international proficiency testing program for a neutralizing
antibody assay for HIV-1 in TZM-bl cells. J. Immunol. Methods,
375(1-2):
57-67. PMID:
21968254
-
Sarzotti-Kelsoe et al. 2014. Optimization and Validation of the
TZM-bl Assay for Standardized Assessments of Neutralizing
Antibodies Against HIV-1. J. Immunol. Methods, 409:
131-46. PMID:
24291345
-
Hraber et al. 2014. Prevalence of Broadly Neutralizing Antibody
Responses During Chronic HIV-1 Infection. AIDS, 28(2):
163-9. PMID:
24361678
-
deCamp et al. 2014. Global Panel of HIV-1 Env Reference Strains
for Standardized Assessments of Vaccine-Elicited Neutralizing
Antibodies. J. Virol., 88(5):
2489-507. PMID:
24352443
-
Hraber et al. 2014. Impact of Clade, Geography, and Age of the
Epidemic on HIV-1 Neutralization by Antibodies. J. Virol.,
88(21):
12623-43. PMID:
25142591
-
Wagh et al. 2016. Optimal combinations of broadly neutralizing
antibodies for prevention and treatment of HIV-1 clade C
infection. PLoS Pathog., 12(3):e1005520.
PMID: 27028935
-
Rademeyer et al. 2016. Features of recently transmitted HIV-1
clade C viruses that impact antibody recognition: Implications
for active and passive immunization. PLoS Pathog,
12(7):e1005742. PMID:
28945784
-
Hraber et al. 2017. Panels of HIV-1 subtype C Env reference
strains for standardized neutralization assessments. J. Virol.,
91(19), pii: e00991-17.
PMID:
28747500
-
Seaman et al. 2020. Optimization and Qualification of a
Functional Anti-Drug Antibody Assay for HIV-1
bnAbs. J. Immuol. Methods, 479:112736.
PMID:
31917969
Reference Reagents: