Enhancement of recombinant adenovirus vaccine-induced primary but not secondary systemic and mucosal immune responses by all-trans retinoic acid.
Vaccination is an important tool for enhancing immune responses against mucosal pathogens. Intramuscularly administered adenovirus (Ad) vectors have been demonstrated to be strong inducers of both systemic and mucosal immune responses. Further enhancement of immune responses following Ad vaccination is highly desirable. All-trans retinoic acid (ATRA), a biologically active vitamin A metabolite, has been explored as an adjuvant for primary immune responses following vaccination. In this study, we investigated the effect of ATRA on a heterologous Ad prime boost regimen. ATRA co-administration during priming increased mucosal and systemic antibody responses as well as mucosal but not systemic CD8(+) T cell responses. However, this effect was no longer apparent after boosting regardless of whether ATRA was administered at the time of priming, at the time of boosting, or at both immunizations. Our findings confirm ATRA as an adjuvant for primary immune responses and suggest that the adjuvant effect does not extend to secondary immune responses.
Wistar Institute, Philadelphia, PA, United States; Gene Therapy and Vaccines Graduate Group of the University of Pennsylvania, Philadelphia, PA, United States.
Steven
S
Tuyishime
Wistar Institute, Philadelphia, PA, United States.
Larissa H
LH
Haut
Wistar Institute, Philadelphia, PA, United States.
Caihong
C
Zhu
Wistar Institute, Philadelphia, PA, United States. Electronic address: ertl@wistar.upenn.edu.
Hildegund C J
HC
Ertl
D016915:AIDS Vaccines / Q000276:immunology*; D000256:Adenoviridae / Q000276:immunology; D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D005822:Genetic Vectors / Q000276:immunology*; D018928:Immunity, Mucosal; D007117:Immunization, Secondary; D008807:Mice, Inbred BALB C; D054388:Receptors, CCR / Q000378:metabolism; D013154:Spleen / Q000276:immunology; D014212:Tretinoin / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000276:immunology
D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; C119309:CC chemokine receptor 9; D054388:Receptors, CCR; D014614:Vaccines, Synthetic; D054301:gag Gene Products, Human Immunodeficiency Virus; D014212:Tretinoin
Adenovirus; All-trans retinoic acid (ATRA); CD8(+) T cells