Almond, Neil

Berkhout, Ben

Berry, Neil

Cranage, Martin

Das, Atze

Elsley, William

Ferguson, Deborah

Klaver, Bep

Kleibeuker, Wendy

Li, Bo

Manoussaka, Maria

Page, Mark

Quartey-Papafio, Ruby

Robinson, Mark

Stebbings, Richard

Tudor, Hannah

English

PubMed

Neil Berry

Atze Das

Mark Page

Hannah Tudor

Mark Robinson

Ruby Quartey-Papafio

William Elsley

Deborah Ferguson

Bo Li

Wendy Kleibeuker

Bep Klaver

Maria Manoussaka

Richard Stebbings

Martin Cranage

Ben Berkhout

Neil Almond

Springer - Publisher Connector

Replication kinetics and persistence of a conditionally live attenuated SIV (SIVrtTA) in vivo confers protection against SIVmac239 wild-type challenge in a rhesus macaque model

BioMed CentralRetrovirology
ssOpen AccePoster presentation
Replication kinetics and persistence of a conditionally live 
attenuated SIV (SIVrtTA) in vivo confers protection against 
SIVmac239 wild-type challenge in a rhesus macaque model
Neil Berry*1, Atze Das2, Mark Page1, Hannah Tudor1, Mark Robinson1, 
Ruby Quartey-Papafio1, William Elsley1, Deborah Ferguson1, Bo Li1, 
Wendy Kleibeuker2, Bep Klaver2, Maria Manoussaka3, Richard Stebbings1, 
Martin Cranage3, Ben Berkhout2 and Neil Almond1
Address: 1NIBSC, Division of Retrovirology, Health Protection Agency, South Mimms, Herts, EN6 3QG , UK, 2Laboratory of Experimental 
Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center of the 
University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands and 3Division of Cellular and Molecular Medicine, St. George's 
University of London, London, SW17 0RE, UK
* Corresponding author    
Vaccination with live attenuated SIV confers potent pro-
tection against wild-type SIV challenge in the SIV/
macaque model of HIV. Although safety concerns pre-
clude the direct application of this vaccine approach in
humans, a clearer understanding of its mechanism of pro-
tection may lead to the development of novel AIDS vac-
cines. A novel live attenuated SIVmac239 Δnef vaccine
(SIVrtTA), dependent on doxycycline administration for
replication, has been evaluated in vivo and its ability to
protect against pathogenic SIV challenge determined. Two
groups of six Indian rhesus macaques (Groups A and B)
were vaccinated with SIVrtTA with an oral doxycycline
dosing regime for 6 months. In Group A, doxycycline was
stopped for 8 weeks before wtSIVmac239 challenge. A
third group was vaccinated with a conventional
SIVmac239Δnef vaccine. In the presence of doxycycline,
all 12 macaques receiving SIVrtTA were infected exhibit-
ing peak SIV RNA levels (log10 3-5 SIV RNA copies/ml)
which declined in all macaques but persisted at higher lev-
els in three SIVrtTA vaccinates. Levels of virus replication
measured by independent qRT-PCR and qDNA PCR
assays were lower in SIVrtTA vaccinates compared with
the SIVmac239Δnef vaccine which peaked in the log10 4-6
SIV RNA copies/ml range. No escape from doxycycline
dependence was identified. Upon challenge with wild-
type SIVmac239 and compared with naive challenge con-
trols (Group D), a significant vaccine effect was observed
in all three vaccine groups, assessed by the comparative
reduction of circulating viral RNA in plasma. Naive
wtSIVmac239 challenge controls exhibited ~7 log10 SIV
RNA copies/ml at peak which persisted beyond the acute
infection phase. This compared with all three vaccine
groups where post wtSIVmac239 viral RNA levels were
markedly reduced among SIVrtTA vaccinates with a more
pronounced vaccine effect among Group A vaccinates.
Viral RNA was un-detectable in one SIVrtTA vaccinate
(Group A) and in the 2 log10 range in another (Group B).
The highest levels of protection in SIVrtTA vaccinates cor-
related with an enhanced persistence of SIVrtTA as circu-
lating viral RNA in the immediate post-acute infection
vaccine period. Retrospective sequence analysis recovered
from SIVrtTA vaccinates indicated a selection of sequence
variants in the LTR promoter region and the Tat and rtTA
genes that do not affect doxycycline control but which
may have influenced replication in vivo. Vaccination with
SIVrtTA induced a marked vaccine effect which will enable
from Frontiers of Retrovirology: Complex retroviruses, retroelements and their hosts
Montpellier, France. 21-23 September 2009
Published: 24 September 2009
Retrovirology 2009, 6(Suppl 2):P13 doi:10.1186/1742-4690-6-S2-P13
<supplement> <title> <p>Frontiers of Retrovirology: Complex retroviruses, retroelements and their hosts</p> </title> <note>Meeting abstracts - A single PDF containing all abstracts in this Supplement is available <a href="http://www.biomedcentral.com/content/files/pdf/1742-4690-6-S2-full.pdf">here</a>.</note> <url>http://www.biomedcentral.com/content/pdf/1742-4690-6-S2-info.pdf</url> </supplement>
This abstract is available from: http://www.retrovirology.com/content/6/S2/P13
© 2009 Berry et al; licensee BioMed Central Ltd. Page 1 of 2
(page number not for citation purposes)
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the role of viral persistence to be evaluated in this vaccina-
tion strategy. SIVrtTA represents a new tool to develop and
design novel AIDS vaccines.Page 2 of 2
(page number not for citation purposes)


Cranage Martin

Manoussaka Maria

Stebbings Richard

Klaver Bep

Kleibeuker Wendy

Li Bo

Ferguson Deborah

Elsley William

Quartey-Papafio Ruby

Robinson Mark

Tudor Hannah

Page Mark

Das Atze

Berry Neil

Berkhout Ben

Almond Neil

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Replication kinetics and persistence of a conditionally live attenuated SIV (SIVrtTA) <it>in vivo </it>confers protection against SIVmac239 wild-type challenge in a rhesus macaque model

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Replication kinetics and persistence of a conditionally live attenuated SIV (SIVrtTA) in vivo confers protection against SIVmac239 wild-type challenge in a rhesus macaque model

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