Hanneke Schuitemaker

Marit van Gils

Naomi Verwer

Rogier Sanders

Tom van den Kerkhof

Zelda Euler

PubMed

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HIV-1 envelope characteristics that coincide with the development of cross-reactive neutralizing activity in HIV-1 infected patients

POSTER PRESENTATION Open Access
HIV-1 envelope characteristics that coincide with
the development of cross-reactive neutralizing
activity in HIV-1 infected patients
Tom van den Kerkhof1*, Marit van Gils1, Zelda Euler1, Naomi Verwer1, Rogier Sanders2, Hanneke Schuitemaker1
From Frontiers of Retrovirology 2011
Amsterdam, The Netherlands. 3-5 October 2011
Background
The HIV-1 envelope glycoprotein (Env) on the viral sur-
face is the target for anti-HIV-1 neutralizing antibodies.
In some HIV-1 infected patients broadly neutralizing
antibodies (BrNAb) develop that neutralise HIV-1 from
different subtypes and therefore are considered to be
directed against conserved regions [2]. The most vulner-
able epitopes can be shielded from antibody recognition
by steric hindrance and N-linked glycans [3]. Moreover,
length and glycosylation of the envelope V1V2 region
seem to play a role in resistance against neutralizing
antibodies [4]. Understanding of factors involved in
BrNAb development will help the rational design of an
effective antibody-based vaccine immunogen.
Methods
From a previous screening of 299 patients for broadly
neutralizing activity (BrNAc), we selected 13 patients
with high BrNAc in serum, 9 patients without BrNAc
(non-BrNAc) and 10 patients with intermediate BrNAc,
at 2-4 years after SC. From these patients clonal viruses
were obtained within the first year after SC from which
gp160 was sequenced and analyzed for length of differ-
ent regions and number of potential N-linked glycosyla-
tion sites (PNGS). Additionally we tested the
neutralization sensitivity of the viral variants from the
patients with and without BrNAc against different
already identified broadly neutralizing antibodies
(BrNAbs).
Results
We observed a correlation between length of the vari-
able regions 1 and 2 (V1V2) of env, especially for vari-
able region 1 (V1), and the presence of BrNAc. Patients
with non-BrNAc in their serum had HIV-1 variants
with longer V1 regions. Remarkably, differences in
length of the V1 region did not coincide with differences
in the number of PNGS on V1. Only the number of
PNGS in gp41 correlated with BrNAc, where a higher
number of PNGS correlated with the absence of BrNAc.
No significant differences were observed between HIV-1
variants from individuals with and without BrNAc in
their sensitivity to the known BrNAbs b12, 2G12, 2F5,
4E10, PG9, PG16 and VRCO1.
Conclusion
The observed correlation between a shorter V1 of env in
patients with BrNAc could indicate that the develop-
ment of BrNAc in HIV-1 infected patients is associated
with a more accessible and more open structure of the
viral envelope glycoprotein, which is achieved by having
fewer glycans and shorter variable loops. However these
env characteristics on early viruses isolated from
patients who developed BrNAc did not coincide with a
higher sensitivity to BrNAbs as compared to early
viruses from patients who did not developed BrNAc.
Identification of env characteristics that coincide with
BrNAc in patients could help the rational design of an
effective antibody-based vaccine immunogen.
Author details
1Dept of Exp Immunology and Landsteíner Laboratory of the Academic
Medical Center at the University of Amsterdam, Amsterdam 1105 AZ, The
Netherlands. 2Dept of Med Microbiology and Experimental Virology of the
Academic Medical Center at the University of Amsterdam, Amsterdam 1105
AZ, The Netherlands.
1Dept of Exp Immunology and Landsteíner Laboratory of the Academic
Medical Center at the University of Amsterdam, Amsterdam 1105 AZ, The
Netherlands
Full list of author information is available at the end of the article
van den Kerkhof et al. Retrovirology 2011, 8(Suppl 2):P69
http://www.retrovirology.com/content/8/S2/P69
© 2011 van den Kerkhof et al; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative
Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly cited.
Published: 3 October 2011
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doi:10.1186/1742-4690-8-S2-P69
Cite this article as: van den Kerkhof et al.: HIV-1 envelope characteristics
that coincide with the development of cross-reactive neutralizing
activity in HIV-1 infected patients. Retrovirology 2011 8(Suppl 2):P69.
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van den Kerkhof et al. Retrovirology 2011, 8(Suppl 2):P69
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Page 2 of 2


Broad HIV-1 neutralization mediated by CD4-binding site antibodies. Nat.Med

GM: Antibody neutralization and escape by HIV-1. Nature

Profiling the specificity of neutralizing antibodies in a large panel of plasmas from patients chronically infected with human immunodeficiency virus type 1 subtypes B and C. J.Virol

Submit your next manuscript to BioMed Central and take full advantage of: • Convenient online submission • Thorough peer review • No space constraints or color ﬁgure charges • Immediate publication on acceptance

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HIV-1 envelope characteristics that coincide with the development of cross-reactive neutralizing activity in HIV-1 infected patients

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