title: The role of follicular helper T cells and the germinal center in HIV-1 gp120 DNA prime and gp120 protein boost vaccination.
abstract: The importance of follicular T helper (TFH) cells and the germinal center (GC) reaction in the humoral immune response has become clear in recent years, however the role of TFH cells and the GC in an HIV vaccine strategy remains unclear. In this study, we primed mice with gp120-encoding DNA and boosted with gp120 protein, a regimen previously shown to induce high titers of high affinity and cross-reactive anti-gp120 Abs. Priming with gp120 DNA caused increased TFH cell differentiation, GC B cells, and antigen-specific antibody titers, compared with priming with gp120 protein. Priming with DNA also caused more activated CD4(+) T cells to become TFH cells and more GC B cells to become memory cells. Deletion of BCL6 midway through the vaccine regimen resulted in loss of TFH cells and GCs, and, unexpectedly, increased anti-gp120 IgG titers and avidity. Our data suggests vaccination with gp120-encoding DNA elicits a stronger and more rapid TFH and GC response than gp120 protein. Furthermore, we demonstrate that the GC reaction may actually limit antigen-specific IgG secretion in the context of repeated immunizations.
authors.affiliation: a Department of Microbiology and Immunology; Indiana University School of Medicine; Indianapolis, IN USA.
authors.forename: Kristin
authors.initials: K
authors.lastname: Hollister
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Chen
authors.forename: Shixia
authors.initials: S
authors.lastname: Wang
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
authors.forename: Arpita
authors.initials: A
authors.lastname: Mondal
authors.forename: Ninah
authors.initials: N
authors.lastname: Clegg
authors.forename: Shan
authors.initials: S
authors.lastname: Lu
authors.forename: Alexander
authors.initials: A
authors.lastname: Dent
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D018858:Germinal Center / Q000166:cytology*; D015483:HIV Antibodies / Q000097:blood; D015699:HIV Envelope Protein gp120 / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D008810:Mice, Inbred C57BL; D051560:Proto-Oncogene Proteins c-bcl-6; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D014611:Vaccination / Q000379:methods; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; C490010:Bcl6 protein, mouse; D004268:DNA-Binding Proteins; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D007074:Immunoglobulin G; D051560:Proto-Oncogene Proteins c-bcl-6; D019444:Vaccines, DNA; D022223:Vaccines, Subunit; C514793:gp120 protein, Human immunodeficiency virus 1
keywords: BCL6; HIV vaccine; follicular helper T cells; germinal center; prime-boost