Buzby, A

Douek, D

Gilbert, P

Graham, B

Hudgens, M

Koup, R

Letvin, N

Mascola, J

Nabel, G

Rao, S

Roederer, M

Seder, R

Retrovirology

English

PubMed

Springer - Publisher Connector

BioMed Central
Page 1 of 1
(page number not for citation purposes)
Retrovirology
Open AccessPoster presentation
P19-57 LB. Gene-based vaccination protects against mucosal 
infection by a heterologous highly pathogenic SIV isolate in rhesus 
monkeys
N Letvin1, J Mascola*2, S Rao2, A Buzby1, M Roederer2, M Hudgens3, 
P Gilbert4, R Seder2, D Douek2, R Koup2, B Graham2 and G Nabel2
Address: 1Beth Israel Deaconess Hospital, Harvard Medical School, Boston, MA, USA, 2Vaccine Research Center, NIAID, NIH, Bethesda, MD, USA, 
3University of North Carolina at Chapel Hill, Chapel Hill, NC, USA and 4Fred Hutchinson Cancer Research Center, Seattle, WA, USA
* Corresponding author    
Background
A goal of an AIDS vaccine is to prevent acquisition of HIV-
1 infection. The ability of AIDS vaccine candidates to pro-
tect against mucosal infection by heterologous viruses in
non-human primates will help to define mechanisms and
correlates of immune protection relevant to humans.
Methods
Rhesus monkeys were immunized intramuscularly using
a plasmid DNA prime/recombinant Ad5 boost regimen.
Experimental animals received vectors expressing genes
encoding SIVmac239 env and gag/pol, and control ani-
mals received empty vectors. Monkeys were challenged 4
months after their final immunization with a series of 12
weekly intra-rectal exposures of SIVsmE660 in one study,
and SIVmac251 in a second study. The challenge dose for
each virus was titered to achieve ~50% infection per-inoc-
ulation for control animals. Time to acquisition of infec-
tion was monitored by weekly assessment of plasma SIV
RNA levels.
Results
Experimentally vaccinated monkeys were significantly
protected against infection by the heterologous virus,
SIVsmE660 (n = 25 per arm). There was a 50% reduction
in acquisition of infection and a significant increase in
time to infection in vaccinated animals as compared to
the control animals (log-rank test, p = 0.0009). There was
no significant difference in peak viral loads of infected
vaccinated animals compared to infected controls.
Immune correlates of vaccine protection are being evalu-
ated. A similar vaccine regimen revealed no protection
from acquisition of infection when homologous
SIVmac251 was used as the challenge virus, and effects on
viral load seen previously with this virus are under inves-
tigation.
Conclusion
This study demonstrates vaccine protection against
mucosal acquisition of a heterologous, pathogenic SIV
isolate in rhesus monkeys. The absence of protection
against acquisition of another pathogenic SIV isolate illus-
trates the biological variability of primate immunodefi-
ciency viruses. Protection in a heterologous challenge
model will permit definition of immune correlates of pro-
tection and facilitate the development of highly effective
AIDS vaccines.
from AIDS Vaccine 2009
Paris, France. 19-22 October 2009
Published: 22 October 2009
Retrovirology 2009, 6(Suppl 3):P421 doi:10.1186/1742-4690-6-S3-P421
<supplement> <title> <p>AIDS Vaccine 2009</p> </title> <editor>Anna Laura Ross</editor> <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-S3-full.pdf">here</a>.</note> <url>http://www.biomedcentral.com/content/pdf/1471-2105-10-S12-info.pdf</url> </supplement>
This abstract is available from: http://www.retrovirology.com/content/6/S3/P421
© 2009 Letvin et al; licensee BioMed Central Ltd. 


P19-57 LB. Gene-based vaccination protects against mucosal infection by a heterologous highly pathogenic SIV isolate in rhesus monkeys

N Letvin

J Mascola

S Rao

A Buzby

M Roederer

M Hudgens

P Gilbert

R Seder

D Douek

R Koup

B Graham

G Nabel

Crossref

Letvin, Norman Lee

Harvard University - DASH 

 P19-57 LB. Gene-Based Vaccination Protects Against MucosalInfection by a Heterologous Highly Pathogenic SIV Isolate inRhesus Monkeys  (Article begins on next page)The Harvard community has made this article openly available.Please share how this access benefits you. Your story matters.Citation Letvin, N., J. Mascola, S. Rao, A. Buzby, M. Roederer, M.Hudgens, P. Gilbert, et al. 2009. P19-57 LB. Gene-basedvaccination protects against mucosal infection by a heterologoushighly pathogenic SIV isolate in rhesus monkeys. Retrovirology6(Suppl 3): P421.Published Version doi:10.1186/1742-4690-6-S3-P421Accessed February 19, 2015 8:10:29 AM ESTCitable Link http://nrs.harvard.edu/urn-3:HUL.InstRepos:4874786Terms of Use This article was downloaded from Harvard University's DASHrepository, and is made available under the terms and conditionsapplicable to Other Posted Material, as set forth athttp://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAABioMed  CentralPage 1 of 1(page number not for citation purposes)RetrovirologyOpen Access Poster presentationP19-57 LB. Gene-based vaccination protects against mucosal infection by a heterologous highly pathogenic SIV isolate in rhesus monkeysN Letvin1, J Mascola*2, S Rao2, A Buzby1, M Roederer2, M Hudgens3, P Gilbert4, R Seder2, D Douek2, R Koup2, B Graham2 and G Nabel2Address: 1Beth Israel Deaconess Hospital, Harvard Medical School, Boston, MA, USA, 2Vaccine Research Center, NIAID, NIH, Bethesda, MD, USA, 3University of North Carolina at Chapel Hill, Chapel Hill, NC, USA and 4Fred Hutchinson Cancer Research Center, Seattle, WA, USA* Corresponding author    BackgroundA goal of an AIDS vaccine is to prevent acquisition of HIV-1 infection. The ability of AIDS vaccine candidates to pro-tect against mucosal infection by heterologous viruses innon-human primates will help to define mechanisms andcorrelates of immune protection relevant to humans.MethodsRhesus monkeys were immunized intramuscularly usinga plasmid DNA prime/recombinant Ad5 boost regimen.Experimental animals received vectors expressing genesencoding SIVmac239 env and gag/pol, and control ani-mals received empty vectors. Monkeys were challenged 4months after their final immunization with a series of 12weekly intra-rectal exposures of SIVsmE660 in one study,and SIVmac251 in a second study. The challenge dose foreach virus was titered to achieve ~50% infection per-inoc-ulation for control animals. Time to acquisition of infec-tion was monitored by weekly assessment of plasma SIVRNA levels.ResultsExperimentally vaccinated monkeys were significantlyprotected against infection by the heterologous virus,SIVsmE660 (n = 25 per arm). There was a 50% reductionin acquisition of infection and a significant increase intime to infection in vaccinated animals as compared tothe control animals (log-rank test, p = 0.0009). There wasno significant difference in peak viral loads of infectedvaccinated animals compared to infected controls.Immune correlates of vaccine protection are being evalu-ated. A similar vaccine regimen revealed no protectionfrom acquisition of infection when homologousSIVmac251 was used as the challenge virus, and effects onviral load seen previously with this virus are under inves-tigation.ConclusionThis study demonstrates vaccine protection againstmucosal acquisition of a heterologous, pathogenic SIVisolate in rhesus monkeys. The absence of protectionagainst acquisition of another pathogenic SIV isolate illus-trates the biological variability of primate immunodefi-ciency viruses. Protection in a heterologous challengemodel will permit definition of immune correlates of pro-tection and facilitate the development of highly effectiveAIDS vaccines.from AIDS Vaccine 2009Paris, France. 19-22 October 2009Published: 22 October 2009Retrovirology 2009, 6(Suppl 3):P421 doi:10.1186/1742-4690-6-S3-P421<supplement> <title> <p>AIDS Vaccine 2009</p> </title> <editor>Anna Laura Ross</editor> <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-S3-full.pdf">here</a>.</note> <url>http://www.biomedcentral.com/content/pdf/1471-2105-10-S12-info.pdf</url> </supplement>This abstract is available from: http://www.retrovirology.com/content/6/S3/P421© 2009 Letvin et al; licensee BioMed Central Ltd. 

P19-57 LB. Gene-Based Vaccination Protects Against Mucosal Infection by a Heterologous Highly Pathogenic SIV Isolate in Rhesus Monkeys

http://dash.harvard.edu/bitstream/handle/1/4874786/2767939.pdf?sequence=1

P19-57 LB. Gene-based vaccination protects against mucosal infection by a heterologous highly pathogenic SIV isolate in rhesus monkeys

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