Systemic immunization with CCL27/CTACK modulates immune responses at mucosal sites in mice and macaques.
Plasmid DNA is a promising vaccine platform that has been shown to be safe and able to be administered repeatedly without vector interference. Enhancing the potency of DNA vaccination through co-delivery of molecular adjuvants is one strategy currently under investigation. Here we describe the use of the novel chemokine adjuvant CCL27/CTACK to enhance immune responses to an HIV-1 or SIV antigen in mice and rhesus macaques. CCL27 has been shown to play a role in inflammatory responses through chemotaxis of CCR10+ cells, and we hypothesized that CCL27 may modulate adaptive immune responses. Immunizations in mice with HIV-1gag/CCL27 enhanced immune responses both at peripheral and, surprisingly, at mucosal sites. To confirm these findings in a large-animal model, we created optimized CCL27 and SIV antigenic plasmid constructs for rhesus macaques. 10 macaques (n=5/group) were immunized intramuscularly with 1mg/construct of antigenic plasmids+/-CCL27 with electroporation. We observed significant IFN-gamma secretion and CD8+ T-cell proliferation in peripheral blood. Interestingly, CCL27 co-immunized macaques exhibited a trend toward greater effector CD4+ T cells in the bronchiolar lavage (BAL). CCL27 co-delivery also elicited greater antigen-specific IgA at unique sites including BAL and fecal samples but not in the periphery. Future studies incorporating CCL27 as an adjuvant in vaccine or therapy models where eliciting immune responses in the lung are warranted.
Kraynyak
Kimberly A
KA
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6100, United States.
Kutzler
Michele A
MA
Cisper
Neil J
NJ
Khan
Amir S
AS
Draghia-Akli
Ruxandra
R
Sardesal
Niranjan Y
NY
Lewis
Mark G
MG
Yan
Jian
J
Weiner
David B
DB
D016915:AIDS Vaccines / Q000276:immunology; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D054425:Chemokine CCL27 / Q000235:genetics / Q000276:immunology*; D005260:Female; D007114:Immunization; D007070:Immunoglobulin A / Q000276:immunology; D007371:Interferon-gamma; D008251:Macaca; D051379:Mice; D008807:Mice, Inbred BALB C; D009092:Mucous Membrane / Q000276:immunology; D010957:Plasmids; D018449:SAIDS Vaccines / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control*; D014162:Transfection; D019444:Vaccines, DNA / Q000276:immunology*; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000276:immunology
D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D054425:Chemokine CCL27; D007070:Immunoglobulin A; D018449:SAIDS Vaccines; D019444:Vaccines, DNA; D054301:gag Gene Products, Human Immunodeficiency Virus; D007371:Interferon-gamma