Long-term persistence of immunity induced by OVA-coupled gas-filled microbubble vaccination partially protects mice against infection by OVA-expressing Listeria.
Vaccination aims at generating memory immune responses able to protect individuals against pathogenic challenges over long periods of time. Subunit vaccine formulations based on safe, but poorly immunogenic, antigenic entities must be combined with adjuvant molecules to make them efficient against infections. We have previously shown that gas-filled microbubbles (MB) are potent antigen-delivery systems. This study compares the ability of various ovalbumin-associated MB (OVA-MB) formulations to induce antigen-specific memory immune responses and evaluates long-term protection toward bacterial infections. When initially testing dendritic cells reactivity to MB constituents, palmitic acid exhibited the highest degree of activation. Subcutaneous immunization of naïve wild-type mice with the OVA-MB formulation comprising the highest palmitic acid content and devoid of PEG2000 was found to trigger the more pronounced Th1-type response, as reflected by robust IFN-γ and IL-2 production. Both T cell and antibody responses persisted for at least 6 months after immunization. At that time, systemic infection with OVA-expressing Listeria monocytgenes was performed. Partial protection of vaccinated mice was demonstrated by reduction of the bacterial load in both the spleen and liver. We conclude that antigen-bound MB exhibit promising properties as a vaccine candidate ensuring prolonged maintenance of protective immunity.
R&D Laboratory, Division of Immunology and Allergy, University State Hospital (CHUV), CLE-D2-204, Chemin des Boveresses 155, 1066 Epalinges, Switzerland.
Gilles
G
Bioley
Bracco Suisse SA, Route de la Galaise 31, 1228 Plan-Les-Ouates, Switzerland.
Anne
A
Lassus
Bracco Suisse SA, Route de la Galaise 31, 1228 Plan-Les-Ouates, Switzerland.
Jacques
J
Terrettaz
Bracco Suisse SA, Route de la Galaise 31, 1228 Plan-Les-Ouates, Switzerland.
François
F
Tranquart
R&D Laboratory, Division of Immunology and Allergy, University State Hospital (CHUV), CLE-D2-204, Chemin des Boveresses 155, 1066 Epalinges, Switzerland. Electronic address: Blaise.Corthesy@chuv.ch.
Blaise
B
Corthésy
D000818:Animals; D001428:Bacterial Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D005260:Female; D015870:Gene Expression; D016908:Gram-Positive Bacterial Infections / Q000276:immunology / Q000517:prevention & control*; D006801:Humans; D007109:Immunity; D007371:Interferon-gamma / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D008087:Listeria / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D045423:Microbubbles; D010047:Ovalbumin / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D011995:Recombination, Genetic; D014611:Vaccination
D001428:Bacterial Vaccines; D007376:Interleukin-2; D007371:Interferon-gamma; D010047:Ovalbumin
Antibody; Bacterial infection; Memory; Protection; T cells; Vaccine