B Keele

C Fenizia

D Montefiori

D Stablein

D Venzon

E Billings

G Ferrari

G Franchini

J Kim

J Lifson

J Tartaglia

L Hudacik

M Doster

M Rao

MG Ferrari

N Michael

P Pegu

R Pal

S Gordon

S Whitney

Y Guan

Retrovirology

PubMed

Springer - Publisher Connector

ORAL PRESENTATION Open Access
Antibodies to the envelope protein protect
macaques from SIVmac251 acquisition in an
immunization regimen that mimics the RV-144
Thai trial
G Franchini1*, P Pegu1, S Gordon1, B Keele2, M Doster1, Y Guan3, G Ferrari4, R Pal5, MG Ferrari6, S Whitney7,
L Hudacik7, E Billings8, M Rao8, D Montefiori9, D Venzon1, C Fenizia1, J Lifson2, D Stablein2, J Tartaglia10,
N Michael11, J Kim12
From AIDS Vaccine 2012
Boston, MA, USA. 9-12 September 2012
Background
The canarypox vector ALVAC-HIV, together with the
HIV gp120 envelope, has protected 31.2% of Thai hetero-
sexual individuals from HIV acquisition in the RV144 HIV
vaccine trial. This outcome was unexpected, given the lim-
ited ability of the ALVAC-HIV vaccine component to
induce CD8+T-cell responses, and of the HIVgp120 envel-
ope to elicit broad neutralizing antibodies.
Methods
We vaccinated macaques with an immunization regimen
that mimics the RV144 trial and exposed them to a muco-
sal dose of SIVmac251 that transmits few virus variants,
similar to HIV transmission to humans.
Results
Vaccination induced anti-envelope antibodies, modest
CD4+ and CD8+ T-cell responses. One third of the vacci-
nated macaques were protected from SIVmac251 acquisi-
tion, whereas the remaining infected vaccinees progressed
to disease. Vaccine induced SIV mac251 specific T-and B-
cell responses were not different in protected or infected
animals. The sera of the animals protected had higher
avidity antibodies to the gp120 envelope protein, recog-
nized the variable envelope region V2, and reduced SIV-
mac251 infectivity in cells that express high level of a4b7,
suggesting a functional role to antibodies to V2.
Conclusion
The SIV mac251 infection macaque faithfully reproduces
results in humans, and is instrumental in the develop-
ment of more efficacious vaccines for HIV.
Author details
1NCI/NIH, Bethesda, MD, USA. 2NCI-Frederick, Frederick, MD, USA. 3Institute of
Human Virology Maryland University School of Medicine, Baltimore, MD,
USA. 4Duke University, Durham, NC, USA. 5Advanced Bioscience Laboratories,
Rockville, MD, USA. 6ABL, Rockville, MD, USA. 7Advanced Biosciences
Laboratories, Rockville, MD, USA. 8Army Institute of Research, Silver Spring,
MD, USA. 9Duke University Medical Center, Durham, NC, USA. 10Sanofi
Pasteur Inc, Swifter, PA, USA. 11Walter Reed Army Intitute of Research, Silver
Spring, MD, USA. 12Walter Reed Army Institute of Research, Sliver Spring, MD,
USA.
Published: 13 September 2012
doi:10.1186/1742-4690-9-S2-O2
Cite this article as: Franchini et al.: Antibodies to the envelope protein
protect macaques from SIVmac251 acquisition in an immunization
regimen that mimics the RV-144 Thai trial. Retrovirology 2012 9(Suppl 2):
O2.
1NCI/NIH, Bethesda, MD, USA
Full list of author information is available at the end of the article
Franchini et al. Retrovirology 2012, 9(Suppl 2):O2
http://www.retrovirology.com/content/9/S2/O2
© 2012 Franchini 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.


Antibodies to the envelope protein protect macaques from SIVmac251 acquisition in an immunization regimen that mimics the RV-144 Thai trial

Crossref

ORAL PRESENTATION Open AccessAntibodies to the envelope protein protectmacaques from SIVmac251 acquisition in animmunization regimen that mimics the RV-144Thai trialG Franchini1*, P Pegu1, S Gordon1, B Keele2, M Doster1, Y Guan3, G Ferrari4, R Pal5, MG Ferrari6, S Whitney7,L Hudacik7, E Billings8, M Rao8, D Montefiori9, D Venzon1, C Fenizia1, J Lifson2, D Stablein2, J Tartaglia10,N Michael11, J Kim12From AIDS Vaccine 2012Boston, MA, USA. 9-12 September 2012BackgroundThe canarypox vector ALVAC-HIV, together with theHIV gp120 envelope, has protected 31.2% of Thai hetero-sexual individuals from HIV acquisition in the RV144 HIVvaccine trial. This outcome was unexpected, given the lim-ited ability of the ALVAC-HIV vaccine component toinduce CD8+T-cell responses, and of the HIVgp120 envel-ope to elicit broad neutralizing antibodies.MethodsWe vaccinated macaques with an immunization regimenthat mimics the RV144 trial and exposed them to a muco-sal dose of SIVmac251 that transmits few virus variants,similar to HIV transmission to humans.ResultsVaccination induced anti-envelope antibodies, modestCD4+ and CD8+ T-cell responses. One third of the vacci-nated macaques were protected from SIVmac251 acquisi-tion, whereas the remaining infected vaccinees progressedto disease. Vaccine induced SIV mac251 specific T-and B-cell responses were not different in protected or infectedanimals. The sera of the animals protected had higheravidity antibodies to the gp120 envelope protein, recog-nized the variable envelope region V2, and reduced SIV-mac251 infectivity in cells that express high level of a4b7,suggesting a functional role to antibodies to V2.ConclusionThe SIV mac251 infection macaque faithfully reproducesresults in humans, and is instrumental in the develop-ment of more efficacious vaccines for HIV.Author details1NCI/NIH, Bethesda, MD, USA. 2NCI-Frederick, Frederick, MD, USA. 3Institute ofHuman Virology Maryland University School of Medicine, Baltimore, MD,USA. 4Duke University, Durham, NC, USA. 5Advanced Bioscience Laboratories,Rockville, MD, USA. 6ABL, Rockville, MD, USA. 7Advanced BiosciencesLaboratories, Rockville, MD, USA. 8Army Institute of Research, Silver Spring,MD, USA. 9Duke University Medical Center, Durham, NC, USA. 10SanofiPasteur Inc, Swifter, PA, USA. 11Walter Reed Army Intitute of Research, SilverSpring, MD, USA. 12Walter Reed Army Institute of Research, Sliver Spring, MD,USA.Published: 13 September 2012doi:10.1186/1742-4690-9-S2-O2Cite this article as: Franchini et al.: Antibodies to the envelope proteinprotect macaques from SIVmac251 acquisition in an immunizationregimen that mimics the RV-144 Thai trial. Retrovirology 2012 9(Suppl 2):O2.1NCI/NIH, Bethesda, MD, USAFull list of author information is available at the end of the articleFranchini et al. Retrovirology 2012, 9(Suppl 2):O2http://www.retrovirology.com/content/9/S2/O2© 2012 Franchini et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the CreativeCommons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, andreproduction in any medium, provided the original work is properly cited.

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Antibodies to the envelope protein protect macaques from SIVmac251 acquisition in an immunization regimen that mimics the RV-144 Thai trial

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