The extradomain A of fibronectin (EDA) combined with poly(I:C) enhances the immune response to HIV-1 p24 protein and the protection against recombinant Listeria monocytogenes-Gag infection in the mouse model.
The development of effective vaccines against HIV-1 infection constitutes one of the major challenges in viral immunology. One of the protein candidates in vaccination against this virus is p24, since it is a conserved HIV antigen that has cytotoxic and helper T cell epitopes as well as B cell epitopes that may jointly confer enhanced protection against infection when used in immunization-challenge approaches. In this context, the adjuvant effect of EDA (used as EDAp24 fusion protein) and poly(I:C), as agonists of TLR4 and TLR3, respectively, was assessed in p24 immunizations using a recombinant Listeria monocytogenes HIV-1 Gag proteins (Lm-Gag, where p24 is the major antigen) for challenge in mice. Immunization with EDAp24 fusion protein together with poly(I:C) adjuvant induced a specific p24 IFN-γ production (Th1 profile) as well as protection against a Lm-Gag challenge, suggesting an additive or synergistic effect between both adjuvants. The combination of EDA (as a fusion protein with the antigen, which may favor antigen targeting to dendritic cells through TLR4) and poly(I:C) could thus be a good adjuvant candidate to enhance the immune response against HIV-1 proteins and its use may open new ways in vaccine investigations on this virus.
Instituto de Agrobiotecnología (CSIC-UPNA-Gobierno de Navarra), Carretera de Mutilva, sn. 31192 Mutilva, Navarra, Spain.
Beatriz
B
San Román
Ximena
X
De Andrés
Pilar-María
PM
Muñoz
Patricia
P
Obregón
Aaron-C
AC
Asensio
Victoria
V
Garrido
Cristina
C
Mansilla
Laura
L
Arribillaga
Juan-José
JJ
Lasarte
Damián
D
De Andrés
Beatriz
B
Amorena
María-Jesús
MJ
Grilló
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D005260:Female; D005353:Fibronectins / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D015683:Gene Products, gag / Q000276:immunology*; D016655:HIV Core Protein p24 / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D007111:Immunity, Cellular / Q000276:immunology; D008089:Listeria monocytogenes / Q000276:immunology; D008088:Listeriosis / Q000517:prevention & control; D051379:Mice; D008807:Mice, Inbred BALB C; D011070:Poly I-C / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000276:immunology
D000276:Adjuvants, Immunologic; D000956:Antigens, Viral; D005353:Fibronectins; D015683:Gene Products, gag; D016655:HIV Core Protein p24; D011993:Recombinant Fusion Proteins; C572454:extra domain A fibronectin, mouse; C514799:p24 protein, Human Immunodeficiency Virus Type 1; D011070:Poly I-C