Genetic impact of vaccination on breakthrough HIV-1 sequences from the STEP trial

Morgane Rolland; Sodsai Tovanabutra; Allan C. Decamp; Nicole Frahm; Peter B. Gilbert; Eric Sanders-Buell; Laura Heath; Craig A. Magaret; Meera Bose; Andrea Bradfield; Annemarie O'Sullivan; Jacqueline Crossler; Teresa Jones; Marty Nau; Kim Wong; Hong Zhao; Dana N. Raugi; Stephanie Sorensen; Julia N. Stoddard; Brandon S. Maust; Wenjie Deng; John Hural; Sheri Dubey; Nelson L. Michael; John Shiver; Lawrence Corey; Fusheng Li; Steve G. Self; Jerome Kim; Susan Buchbinder; Danilo R. Casimiro; Michael N. Robertson; Ann Duerr; M. Juliana McElrath; Francine E. McCutchan; James I. Mullins

doi:10.1038/nm.2316

Genetic impact of vaccination on breakthrough HIV-1 sequences from the STEP trial

Morgane Rolland, Sodsai Tovanabutra, Allan C. Decamp, Nicole Frahm, Peter B. Gilbert, Eric Sanders-Buell, Laura Heath, Craig A. Magaret, Meera Bose, Andrea Bradfield, Annemarie O'Sullivan, Jacqueline Crossler, Teresa Jones, Marty Nau, Kim Wong, Hong Zhao, Dana N. Raugi, Stephanie Sorensen, Julia N. Stoddard, Brandon S. MaustWenjie Deng, John Hural, Sheri Dubey, Nelson L. Michael, John Shiver, Lawrence Corey, Fusheng Li, Steve G. Self, Jerome Kim, Susan Buchbinder, Danilo R. Casimiro, Michael N. Robertson, Ann Duerr, M. Juliana McElrath, Francine E. McCutchan, James I. Mullins

Research output: Contribution to journal › Article › peer-review

198 Scopus citations

Abstract

We analyzed HIV-1 genome sequences from 68 newly infected volunteers in the STEP HIV-1 vaccine trial. To determine whether the vaccine exerted selective T cell pressure on breakthrough viruses, we identified potential T cell epitopes in the founder sequences and compared them to epitopes in the vaccine. We found greater distances to the vaccine sequence for sequences from vaccine recipients than from placebo recipients. The most significant signature site distinguishing vaccine from placebo recipients was Gag amino acid 84, a site encompassed by several epitopes contained in the vaccine and restricted by human leukocyte antigen (HLA) alleles common in the study cohort. Moreover, the extended divergence was confined to the vaccine components of the virus (HIV-1 Gag, Pol and Nef) and not found in other HIV-1 proteins. These results represent what is to our knowledge the first evidence of selective pressure from vaccine-induced T cell responses on HIV-1 infection in humans.

Original language	English
Pages (from-to)	366-372
Number of pages	7
Journal	Nature Medicine
Volume	17
Issue number	3
DOIs	https://doi.org/10.1038/nm.2316
State	Published - Mar 2011
Externally published	Yes

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Rolland, M., Tovanabutra, S., Decamp, A. C., Frahm, N., Gilbert, P. B., Sanders-Buell, E., Heath, L., Magaret, C. A., Bose, M., Bradfield, A., O'Sullivan, A., Crossler, J., Jones, T., Nau, M., Wong, K., Zhao, H., Raugi, D. N., Sorensen, S., Stoddard, J. N., ... Mullins, J. I. (2011). Genetic impact of vaccination on breakthrough HIV-1 sequences from the STEP trial. Nature Medicine, 17(3), 366-372. https://doi.org/10.1038/nm.2316

@article{d60e34cf494a4702be8565f4de03ddb1,

title = "Genetic impact of vaccination on breakthrough HIV-1 sequences from the STEP trial",

abstract = "We analyzed HIV-1 genome sequences from 68 newly infected volunteers in the STEP HIV-1 vaccine trial. To determine whether the vaccine exerted selective T cell pressure on breakthrough viruses, we identified potential T cell epitopes in the founder sequences and compared them to epitopes in the vaccine. We found greater distances to the vaccine sequence for sequences from vaccine recipients than from placebo recipients. The most significant signature site distinguishing vaccine from placebo recipients was Gag amino acid 84, a site encompassed by several epitopes contained in the vaccine and restricted by human leukocyte antigen (HLA) alleles common in the study cohort. Moreover, the extended divergence was confined to the vaccine components of the virus (HIV-1 Gag, Pol and Nef) and not found in other HIV-1 proteins. These results represent what is to our knowledge the first evidence of selective pressure from vaccine-induced T cell responses on HIV-1 infection in humans.",

author = "Morgane Rolland and Sodsai Tovanabutra and Decamp, {Allan C.} and Nicole Frahm and Gilbert, {Peter B.} and Eric Sanders-Buell and Laura Heath and Magaret, {Craig A.} and Meera Bose and Andrea Bradfield and Annemarie O'Sullivan and Jacqueline Crossler and Teresa Jones and Marty Nau and Kim Wong and Hong Zhao and Raugi, {Dana N.} and Stephanie Sorensen and Stoddard, {Julia N.} and Maust, {Brandon S.} and Wenjie Deng and John Hural and Sheri Dubey and Michael, {Nelson L.} and John Shiver and Lawrence Corey and Fusheng Li and Self, {Steve G.} and Jerome Kim and Susan Buchbinder and Casimiro, {Danilo R.} and Robertson, {Michael N.} and Ann Duerr and McElrath, {M. Juliana} and McCutchan, {Francine E.} and Mullins, {James I.}",

note = "Funding Information: We thank the study participants for their time and dedication; the HIV Vaccine Trials Network Laboratory Program, the Statistical Center for HIV/AIDS Research & Prevention and Core staff who contributed to the study implementation and analysis; the Merck functional teams: the Clinical Research Specialist Organization, Worldwide Clinical Data Management Operation, Clinical Research Operations, J.T. Herbeck and B.B. Larsen for comments on the manuscript, and the Clinical Assay and Sample Receiving Operations. This work was supported by US Public Health Service grant AI41505.",

year = "2011",

month = mar,

doi = "10.1038/nm.2316",

language = "English",

volume = "17",

pages = "366--372",

journal = "Nature Medicine",

issn = "1078-8956",

number = "3",

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Rolland, M, Tovanabutra, S, Decamp, AC, Frahm, N, Gilbert, PB, Sanders-Buell, E, Heath, L, Magaret, CA, Bose, M, Bradfield, A, O'Sullivan, A, Crossler, J, Jones, T, Nau, M, Wong, K, Zhao, H, Raugi, DN, Sorensen, S, Stoddard, JN, Maust, BS, Deng, W, Hural, J, Dubey, S, Michael, NL, Shiver, J, Corey, L, Li, F, Self, SG, Kim, J, Buchbinder, S, Casimiro, DR, Robertson, MN, Duerr, A, McElrath, MJ, McCutchan, FE & Mullins, JI 2011, 'Genetic impact of vaccination on breakthrough HIV-1 sequences from the STEP trial', Nature Medicine, vol. 17, no. 3, pp. 366-372. https://doi.org/10.1038/nm.2316

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T1 - Genetic impact of vaccination on breakthrough HIV-1 sequences from the STEP trial

AU - Rolland, Morgane

AU - Tovanabutra, Sodsai

AU - Decamp, Allan C.

AU - Frahm, Nicole

AU - Gilbert, Peter B.

AU - Sanders-Buell, Eric

AU - Heath, Laura

AU - Magaret, Craig A.

AU - Bose, Meera

AU - Bradfield, Andrea

AU - O'Sullivan, Annemarie

AU - Crossler, Jacqueline

AU - Jones, Teresa

AU - Nau, Marty

AU - Wong, Kim

AU - Zhao, Hong

AU - Raugi, Dana N.

AU - Sorensen, Stephanie

AU - Stoddard, Julia N.

AU - Maust, Brandon S.

AU - Deng, Wenjie

AU - Hural, John

AU - Dubey, Sheri

AU - Michael, Nelson L.

AU - Shiver, John

AU - Corey, Lawrence

AU - Li, Fusheng

AU - Self, Steve G.

AU - Kim, Jerome

AU - Buchbinder, Susan

AU - Casimiro, Danilo R.

AU - Robertson, Michael N.

AU - Duerr, Ann

AU - McElrath, M. Juliana

AU - McCutchan, Francine E.

AU - Mullins, James I.

N1 - Funding Information: We thank the study participants for their time and dedication; the HIV Vaccine Trials Network Laboratory Program, the Statistical Center for HIV/AIDS Research & Prevention and Core staff who contributed to the study implementation and analysis; the Merck functional teams: the Clinical Research Specialist Organization, Worldwide Clinical Data Management Operation, Clinical Research Operations, J.T. Herbeck and B.B. Larsen for comments on the manuscript, and the Clinical Assay and Sample Receiving Operations. This work was supported by US Public Health Service grant AI41505.

PY - 2011/3

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N2 - We analyzed HIV-1 genome sequences from 68 newly infected volunteers in the STEP HIV-1 vaccine trial. To determine whether the vaccine exerted selective T cell pressure on breakthrough viruses, we identified potential T cell epitopes in the founder sequences and compared them to epitopes in the vaccine. We found greater distances to the vaccine sequence for sequences from vaccine recipients than from placebo recipients. The most significant signature site distinguishing vaccine from placebo recipients was Gag amino acid 84, a site encompassed by several epitopes contained in the vaccine and restricted by human leukocyte antigen (HLA) alleles common in the study cohort. Moreover, the extended divergence was confined to the vaccine components of the virus (HIV-1 Gag, Pol and Nef) and not found in other HIV-1 proteins. These results represent what is to our knowledge the first evidence of selective pressure from vaccine-induced T cell responses on HIV-1 infection in humans.

AB - We analyzed HIV-1 genome sequences from 68 newly infected volunteers in the STEP HIV-1 vaccine trial. To determine whether the vaccine exerted selective T cell pressure on breakthrough viruses, we identified potential T cell epitopes in the founder sequences and compared them to epitopes in the vaccine. We found greater distances to the vaccine sequence for sequences from vaccine recipients than from placebo recipients. The most significant signature site distinguishing vaccine from placebo recipients was Gag amino acid 84, a site encompassed by several epitopes contained in the vaccine and restricted by human leukocyte antigen (HLA) alleles common in the study cohort. Moreover, the extended divergence was confined to the vaccine components of the virus (HIV-1 Gag, Pol and Nef) and not found in other HIV-1 proteins. These results represent what is to our knowledge the first evidence of selective pressure from vaccine-induced T cell responses on HIV-1 infection in humans.

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DO - 10.1038/nm.2316

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SP - 366

EP - 372

JO - Nature Medicine

JF - Nature Medicine

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ER -

Genetic impact of vaccination on breakthrough HIV-1 sequences from the STEP trial

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