DNA/NYVAC Vaccine Regimen Induces HIV-specific CD4 and CD8 T-cell Responses in Intestinal Mucosa

Overview

Journal J Virol

Publisher American Society for Microbiology

Date 2011 Jul 22

PMID 21775454

Citations 19

Authors

Matthieu Perreau

Hugh C Welles

Alexandre Harari

Olivia Hall

Ricardo Martin

Michel Maillard

Gian Dorta

Pierre-Alexandre Bart

Eric J Kremer

Jim Tartaglia

Ralf Wagner

Mariano Esteban

Yves Levy

Giuseppe Pantaleo

Affiliations

Soon will be listed here.

Abstract

In the present study, we have investigated the anatomic distribution in blood and gut mucosal tissues of memory poxvirus-specific CD4 and CD8 T cells in subjects vaccinated with smallpox and compared it with vector (NYVAC)-specific and HIV insert-specific T-cell responses induced by an experimental DNA-C/ NYVAC-C vaccine regimen. Smallpox-specific CD4 T-cell responses were present in the blood of 52% of the subjects studied, while smallpox-specific CD8 T cells were rarely detected (12%). With one exception, smallpox-specific T cells were not measurable in gut tissues. Interestingly, NYVAC vector-specific and HIV-specific CD4 and CD8 T-cell responses were detected in almost 100% of the subjects immunized with DNA-C/NYVAC-C in blood and gut tissues. The large majority (83%) of NYVAC-specific CD4 T cells expressed α4β7 integrins and the HIV coreceptor CCR5. These results demonstrate that the experimental DNA-C/NYVAC-C HIV vaccine regimen induces the homing of potentially protective HIV-specific CD4 and CD8 T cells in the gut, the port of entry of HIV and one of the major sites for HIV spreading and the depletion of CD4 T cells.

Citing Articles

Pathology-Based Research in Africa.

Lemos M, Taylor T, McGoldrick S, Molyneux M, Menon M, Kussick S Clin Lab Med. 2018; 38(1):67-90.

PMID: 29412886 PMC: 5894888. DOI: 10.1016/j.cll.2017.10.006.

Cell-Mediated Immune Predictors of Vaccine Effect on Viral Load and CD4 Count in a Phase 2 Therapeutic HIV-1 Vaccine Clinical Trial.

Huang Y, Pantaleo G, Tapia G, Sanchez B, Zhang L, Trondsen M EBioMedicine. 2017; 24:195-204.

PMID: 28970080 PMC: 5652289. DOI: 10.1016/j.ebiom.2017.09.028.

DNA Priming Increases Frequency of T-Cell Responses to a Vesicular Stomatitis Virus HIV Vaccine with Specific Enhancement of CD8 T-Cell Responses by Interleukin-12 Plasmid DNA.

Li S, Kochar N, Elizaga M, Hay C, Wilson G, Cohen K Clin Vaccine Immunol. 2017; 24(11).

PMID: 28931520 PMC: 5674193. DOI: 10.1128/CVI.00263-17.

A heterologous prime-boosting strategy with replicating Vaccinia virus vectors and plant-produced HIV-1 Gag/dgp41 virus-like particles.

Meador L, Kessans S, Kilbourne J, Kibler K, Pantaleo G, Roderiguez M Virology. 2017; 507:242-256.

PMID: 28458036 PMC: 5529300. DOI: 10.1016/j.virol.2017.04.008.

HIV/AIDS Vaccine Candidates Based on Replication-Competent Recombinant Poxvirus NYVAC-C-KC Expressing Trimeric gp140 and Gag-Derived Virus-Like Particles or Lacking the Viral Molecule B19 That Inhibits Type I Interferon Activate Relevant....

Garcia-Arriaza J, Perdiguero B, Heeney J, Seaman M, Montefiori D, Yates N J Virol. 2017; 91(9).

PMID: 28179536 PMC: 5391471. DOI: 10.1128/JVI.02182-16.

References

Hutnick N, Carnathan D, Dubey S, Makedonas G, Cox K, Kierstead L . Baseline Ad5 serostatus does not predict Ad5 HIV vaccine-induced expansion of adenovirus-specific CD4+ T cells. Nat Med. 2009; 15(8):876-8. PMC: 2723179. DOI: 10.1038/nm.1989. View

McElrath M, De Rosa S, Moodie Z, Dubey S, Kierstead L, Janes H . HIV-1 vaccine-induced immunity in the test-of-concept Step Study: a case-cohort analysis. Lancet. 2008; 372(9653):1894-1905. PMC: 2774110. DOI: 10.1016/S0140-6736(08)61592-5. View

Shiver J, Emini E . Recent advances in the development of HIV-1 vaccines using replication-incompetent adenovirus vectors. Annu Rev Med. 2004; 55:355-72. DOI: 10.1146/annurev.med.55.091902.104344. View

Perreau M, Pantaleo G, Kremer E . Activation of a dendritic cell-T cell axis by Ad5 immune complexes creates an improved environment for replication of HIV in T cells. J Exp Med. 2008; 205(12):2717-25. PMC: 2585831. DOI: 10.1084/jem.20081786. View

Benlahrech A, Harris J, Meiser A, Papagatsias T, Hornig J, Hayes P . Adenovirus vector vaccination induces expansion of memory CD4 T cells with a mucosal homing phenotype that are readily susceptible to HIV-1. Proc Natl Acad Sci U S A. 2009; 106(47):19940-5. PMC: 2785271. DOI: 10.1073/pnas.0907898106. View

Campbell J, Haraldsen G, Pan J, Rottman J, Qin S, Ponath P . The chemokine receptor CCR4 in vascular recognition by cutaneous but not intestinal memory T cells. Nature. 1999; 400(6746):776-80. DOI: 10.1038/23495. View

Zabel B, Agace W, Campbell J, Heath H, Parent D, Roberts A . Human G protein-coupled receptor GPR-9-6/CC chemokine receptor 9 is selectively expressed on intestinal homing T lymphocytes, mucosal lymphocytes, and thymocytes and is required for thymus-expressed chemokine-mediated chemotaxis. J Exp Med. 1999; 190(9):1241-56. PMC: 2195678. DOI: 10.1084/jem.190.9.1241. View

McWilliams M, Lamm M . Mesenteric lymph node B lymphoblasts which home to the small intestine are precommitted to IgA synthesis. J Exp Med. 1977; 145(4):866-75. PMC: 2180636. DOI: 10.1084/jem.145.4.866. View

Sallusto F, Geginat J, Lanzavecchia A . Central memory and effector memory T cell subsets: function, generation, and maintenance. Annu Rev Immunol. 2004; 22:745-63. DOI: 10.1146/annurev.immunol.22.012703.104702. View

10.

Kantele A, Zivny J, Hakkinen M, Elson C, Mestecky J . Differential homing commitments of antigen-specific T cells after oral or parenteral immunization in humans. J Immunol. 1999; 162(9):5173-7. View

11.

McDermott M, Bienenstock J . Evidence for a common mucosal immunologic system. I. Migration of B immunoblasts into intestinal, respiratory, and genital tissues. J Immunol. 1979; 122(5):1892-8. View

12.

Papadakis K, Prehn J, Nelson V, Cheng L, Binder S, Ponath P . The role of thymus-expressed chemokine and its receptor CCR9 on lymphocytes in the regional specialization of the mucosal immune system. J Immunol. 2000; 165(9):5069-76. DOI: 10.4049/jimmunol.165.9.5069. View

13.

Mittereder N, March K, Trapnell B . Evaluation of the concentration and bioactivity of adenovirus vectors for gene therapy. J Virol. 1996; 70(11):7498-509. PMC: 190817. DOI: 10.1128/JVI.70.11.7498-7509.1996. View

14.

Griscelli C, Vassalli P . The mouse gut T lymphocyte, a novel type of T cell. Nature, origin, and traffic in mice in normal and graft-versus-host conditions. J Exp Med. 1978; 148(6):1661-77. PMC: 2185102. DOI: 10.1084/jem.148.6.1661. View

15.

Guerra S, Najera J, Gonzalez J, Lopez-Fernandez L, Climent N, Gatell J . Distinct gene expression profiling after infection of immature human monocyte-derived dendritic cells by the attenuated poxvirus vectors MVA and NYVAC. J Virol. 2007; 81(16):8707-21. PMC: 1951336. DOI: 10.1128/JVI.00444-07. View

16.

Wagner N, Lohler J, Kunkel E, Ley K, Leung E, Krissansen G . Critical role for beta7 integrins in formation of the gut-associated lymphoid tissue. Nature. 1996; 382(6589):366-70. DOI: 10.1038/382366a0. View

17.

Perreau M, Guerin M, Drouet C, Kremer E . Interactions between human plasma components and a xenogenic adenovirus vector: reduced immunogenicity during gene transfer. Mol Ther. 2007; 15(11):1998-2007. DOI: 10.1038/sj.mt.6300289. View

18.

Perreau M, Mennechet F, Serratrice N, Glasgow J, Curiel D, Wodrich H . Contrasting effects of human, canine, and hybrid adenovirus vectors on the phenotypical and functional maturation of human dendritic cells: implications for clinical efficacy. J Virol. 2007; 81(7):3272-84. PMC: 1866049. DOI: 10.1128/JVI.01530-06. View

19.

Corey L, McElrath M, Kublin J . Post-step modifications for research on HIV vaccines. AIDS. 2008; 23(1):3-8. PMC: 2720076. DOI: 10.1097/QAD.0b013e32830e6d6d. View

20.

Wurbel M, Philippe J, Nguyen C, Victorero G, Freeman T, Wooding P . The chemokine TECK is expressed by thymic and intestinal epithelial cells and attracts double- and single-positive thymocytes expressing the TECK receptor CCR9. Eur J Immunol. 1999; 30(1):262-71. DOI: 10.1002/1521-4141(200001)30:1<262::AID-IMMU262>3.0.CO;2-0. View