Poster Presentation From AIDS Vaccine 2012 Boston, MA, USA. 9-12 September 201

Ardito, M.

Boyle, C. M.

De Groot, Anne S

Koita, O.

Koty, Z.

Levitz, L.

Martin, W.

Moise, Leonard

Rochas, M.

Rozenhal, J.

Sangare, K.

Tounkara, K.

Retrovirology

English

PubMed

AS De Groot

L Moise

O Koita

K Sangare

L Levitz

J Rozenhal

Z Koty

K Tounkara

M Ardito

CM Boyle

M Rochas

W Martin

Crossref

Further confirmation of broadly conserved, highly immunogenic cross-clade HIV CTL epitopes for inclusion in the GAIA HIV vaccine

DigitalCommons@URI

University of Rhode IslandDigitalCommons@URIInstitute for Immunology and Informatics FacultyPublications Institute for Immunology and Informatics (iCubed)2012Further Confirmation of Broadly Conserved,Highly Immunogenic Cross-Clade HIV CTLEpitopes for Inclusion in the GAIA HIV VaccineAnne S. De GrootUniversity of Rhode Island, annied@uri.eduLeonard MoiseUniversity of Rhode Island, lmoise@uri.eduSee next page for additional authorsCreative Commons LicenseThis work is licensed under a Creative Commons Attribution 3.0 License.Follow this and additional works at: https://digitalcommons.uri.edu/immunology_facpubsTerms of UseAll rights reserved under copyright.This Article is brought to you for free and open access by the Institute for Immunology and Informatics (iCubed) at DigitalCommons@URI. It hasbeen accepted for inclusion in Institute for Immunology and Informatics Faculty Publications by an authorized administrator ofDigitalCommons@URI. For more information, please contact digitalcommons@etal.uri.edu.Citation/Publisher AttributionDe Groot, A. S., Moise, L., Koita, O., Sangare, K., Levitz, L., Rozenhal, J., Koty, Z., Tounkara, K., Ardito, M., Boyle, C. M., Rochas, M.,& Martin, W. (2012). Further confirmation of broadly conserved, highly immunogenic cross-clade HIV CTL epitopes for inclusion inthe GAIA HIV vaccine. Retrovirology, 9(Suppl 2), P295.Available at: http://dx.doi.org/10.1186/1742-4690-9-S2-P295AuthorsAnne S. De Groot, Leonard Moise, O. Koita, K. Sangare, L. Levitz, J. Rozenhal, Z. Koty, K. Tounkara, M.Ardito, C. M. Boyle, M. Rochas, and W. MartinThis article is available at DigitalCommons@URI: https://digitalcommons.uri.edu/immunology_facpubs/38POSTER PRESENTATION Open AccessFurther confirmation of broadly conserved, highlyimmunogenic cross-clade HIV CTL epitopes forinclusion in the GAIA HIV vaccineAS De Groot1*, L Moise1, O Koita2, K Sangare2, L Levitz1, J Rozenhal3, Z Koty4, K Tounkara4, M Ardito1, CM Boyle1,M Rochas4, W Martin1From AIDS Vaccine 2012Boston, MA, USA. 9-12 September 2012BackgroundOne of the biggest challenges for HIV vaccine design isidentifying conserved HLA Class I- and Class II-restricted epitopes that would impart substantial fitnesscost to the virus, thereby controlling or preventinginfection. Here, we set out to develop an epitope-driven,DNA-prime/pseudoprotein-boost HIV vaccine (GAIAvaccine) composed of such epitopes.MethodsAnalysis was performed in 2003 on 10,803 HIV-1sequences, and again in 2009, on an expanded set of43,822 sequences. These were searched for conserved 9-10-mer segments with the EpiMatrix suite of immunoin-formatic algorithms. From the most highly conserved(>5% isolates) or top 1,000 scoring 9-mers, HLA Class Ibinding sequences and Class II immunogenic consensussequences (ICS) were identified for vaccine design. Vali-dation was performed in Thailand, the USA, and Malivia in vitro binding and IFN-g ELISpot assays, usingHIV-infected donor peripheral blood. HLA transgenicmice were immunized in DNA-prime/peptide-boost vac-cine studies including these epitopes.Results`Epitopes selected as described are more broadly con-served than those selected for other epitope-based vac-cines (>70%, compared to Epimmune’s 40%). Antigenicityof 98% of ICS epitopes and Class I epitopes (87% A2,29% A3, 67% B7, 20% A24) was confirmed in HIV-infected subjects. Fifteen ICS peptides and 12 A2 peptideswere confirmed in both Mali and the USA. Sixteen A3peptides were confirmed weighting sequences for conser-vation and immunogenicity (as determined by EpiMatrixscore), in vitro binding, and positive ELISpot responses.Epitope immunogenicity was validated in HLA transgenicmouse immunization studies.ConclusionThe GAIA vaccine approach is an effective means oftriaging HIV epitope sequences to identify the mostimmunogenic and conserved epitope candidates acrossHLA allotypes. HLA transgenic mouse studies showedprototype DNA vaccines including these epitopes to beimmunogenic, suggesting the epitope-rich GAIA vaccinewould induce greater immunogenicity than other DNA/viral vector prime-boost vaccines in humans.Author details1EpiVax, Inc, Providence, RI, USA. 2University of Bamako, Bamako, Mali.3Institute of Immunology and Informatics University of Rhode Island,Providence, RI, USA. 4GAIA Vaccine Foundation, Bamako, Mali.Published: 13 September 2012doi:10.1186/1742-4690-9-S2-P295Cite this article as: De Groot et al.: Further confirmation of broadlyconserved, highly immunogenic cross-clade HIV CTL epitopes forinclusion in the GAIA HIV vaccine. Retrovirology 2012 9(Suppl 2):P295.1EpiVax, Inc, Providence, RI, USAFull list of author information is available at the end of the articleDe Groot et al. Retrovirology 2012, 9(Suppl 2):P295http://www.retrovirology.com/content/9/S2/P295© 2012 De Groot 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.

Further Confirmation of Broadly Conserved, Highly Immunogenic Cross-Clade HIV CTL Epitopes for Inclusion in the GAIA HIV Vaccine

Springer - Publisher Connector

POSTER PRESENTATION Open Access
Further confirmation of broadly conserved, highly
immunogenic cross-clade HIV CTL epitopes for
inclusion in the GAIA HIV vaccine
AS De Groot1*, L Moise1, O Koita2, K Sangare2, L Levitz1, J Rozenhal3, Z Koty4, K Tounkara4, M Ardito1, CM Boyle1,
M Rochas4, W Martin1
From AIDS Vaccine 2012
Boston, MA, USA. 9-12 September 2012
Background
One of the biggest challenges for HIV vaccine design is
identifying conserved HLA Class I- and Class II-
restricted epitopes that would impart substantial fitness
cost to the virus, thereby controlling or preventing
infection. Here, we set out to develop an epitope-driven,
DNA-prime/pseudoprotein-boost HIV vaccine (GAIA
vaccine) composed of such epitopes.
Methods
Analysis was performed in 2003 on 10,803 HIV-1
sequences, and again in 2009, on an expanded set of
43,822 sequences. These were searched for conserved 9-
10-mer segments with the EpiMatrix suite of immunoin-
formatic algorithms. From the most highly conserved
(>5% isolates) or top 1,000 scoring 9-mers, HLA Class I
binding sequences and Class II immunogenic consensus
sequences (ICS) were identified for vaccine design. Vali-
dation was performed in Thailand, the USA, and Mali
via in vitro binding and IFN-g ELISpot assays, using
HIV-infected donor peripheral blood. HLA transgenic
mice were immunized in DNA-prime/peptide-boost vac-
cine studies including these epitopes.
Results
`Epitopes selected as described are more broadly con-
served than those selected for other epitope-based vac-
cines (>70%, compared to Epimmune’s 40%). Antigenicity
of 98% of ICS epitopes and Class I epitopes (87% A2,
29% A3, 67% B7, 20% A24) was confirmed in HIV-
infected subjects. Fifteen ICS peptides and 12 A2 peptides
were confirmed in both Mali and the USA. Sixteen A3
peptides were confirmed weighting sequences for conser-
vation and immunogenicity (as determined by EpiMatrix
score), in vitro binding, and positive ELISpot responses.
Epitope immunogenicity was validated in HLA transgenic
mouse immunization studies.
Conclusion
The GAIA vaccine approach is an effective means of
triaging HIV epitope sequences to identify the most
immunogenic and conserved epitope candidates across
HLA allotypes. HLA transgenic mouse studies showed
prototype DNA vaccines including these epitopes to be
immunogenic, suggesting the epitope-rich GAIA vaccine
would induce greater immunogenicity than other DNA/
viral vector prime-boost vaccines in humans.
Author details
1EpiVax, Inc, Providence, RI, USA. 2University of Bamako, Bamako, Mali.
3Institute of Immunology and Informatics University of Rhode Island,
Providence, RI, USA. 4GAIA Vaccine Foundation, Bamako, Mali.
Published: 13 September 2012
doi:10.1186/1742-4690-9-S2-P295
Cite this article as: De Groot et al.: Further confirmation of broadly
conserved, highly immunogenic cross-clade HIV CTL epitopes for
inclusion in the GAIA HIV vaccine. Retrovirology 2012 9(Suppl 2):P295.
1EpiVax, Inc, Providence, RI, USA
Full list of author information is available at the end of the article
De Groot et al. Retrovirology 2012, 9(Suppl 2):P295
http://www.retrovirology.com/content/9/S2/P295
© 2012 De Groot 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.


file:///data/core-remote/dit/data/Springer-OA/pdf/c76/aHR0cDovL2xpbmsuc3ByaW5nZXIuY29tLzEwLjExODYvMTc0Mi00NjkwLTktUzItUDI5NS5wZGY=.pdf

Further Confirmation of Broadly Conserved, Highly Immunogenic Cross-Clade HIV CTL Epitopes for Inclusion in the GAIA HIV Vaccine

Abstract

Similar works

Full text

Available Versions

Crossref

DigitalCommons@URI

Springer - Publisher Connector

Springer - Publisher Connector