Intravaginal immunisation using a novel antigen-releasing ring device elicits robust vaccine antigen-specific systemic and mucosal humoral immune responses

• DOI: 10.1016/j.jconrel.2017.01.018
• Publication Date: 2017-01-21T05:33:23Z
• Authors: Paul F. McKay; Jamie F.S. Mann; Aditya Pattani; Vicky Kett; Yoann Aldon; Deborah King; R. Karl Malcolm; Robin J. Shattock
• Keywords: Chemistry, Multidisciplinary; Pharmaceutical Science; HIV Infections; env Gene Products; HIV Infections/immunology; TOXIN B-SUBUNIT; 0302 clinical medicine; 0903 Biomedical Engineering; HIV-1/immunology; /dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being; name=SDG 3 - Good Health and Well-being; Pharmacology & Pharmacy; Immunoglobulin G/immunology; AIDS Vaccines; Mucosal; Multidisciplinary; INDUCTION; Imidazoles; env Gene Products, Human Immunodeficiency Virus; Humoral; CHOLERA-TOXIN; WOMEN; 600; 3. Good health; Chemistry; AGONIST; INFLUENZA; Administration; Physical Sciences; /dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being; AIDS Vaccines/administration & dosage; Female; Life Sciences & Biomedicine; CONTRACEPTIVE VAGINAL RINGS; ANTIBODY-RESPONSES; Immunologic/administration & dosage; Immunization/instrumentation; 610; Article; 03 medical and health sciences; Adjuvants, Immunologic; Animals; Humans; Adjuvants; Immunity, Mucosal; Science & Technology; Sheep; Intravaginal; GENITAL-TRACT; Immunity; Contraceptive Devices, Female; name=SDG 3 - Good Health and Well-being; Immunity, Humoral; Immunoglobulin A; Administration, Intravaginal; Immunoglobulin A/immunology; Immunoglobulin G; Antibody Formation; HIV-1; Human Immunodeficiency Virus/administration & dosage; 1115 Pharmacology And Pharmaceutical Sciences; Immunization; Contraceptive Devices; ADJUVANTS; Imidazoles/administration & dosage

The generation of effective levels antigen-specific immunity at the mucosal sites pathogen entry is a key goal for vaccinologists. We explored topical vaginal application as an approach to initiate local immunity, enhance previously existing systemic or re-target responses mucosae. To deliver protein vaccine formulation surface, we used novel ring device comprising silicone elastomer body into which three freeze-dried, rod-shaped, hydroxypropylmethylcellulose inserts were incorporated. Each rod contained recombinant HIV-1 CN54gp140 (167 μg) ± R848 adjuvant. loaded cavities within each such that only ends initially exposed. Sheep received prime-boost vaccination regime intramuscular injection 100 μg + 200 followed by successive applications one week duration and separated month intervals. Other sheep devices without priming. Serum fluids sampled every two weeks analysed ELISA B cells measured flow cytometry necropsy. Vaccine serum antibody detected in both intramuscularly-primed mucosally-primed groups. Those animals vaccinations had identical IgG but superior IgA responses. Analysis revealed all exhibited with 30-fold greater than levels. Importantly, very high numbers genital draining lymph nodes. have elicited immune after adjuvanted antigen release device. This regimen delivery method large antigen-reactive cells, likely essential protection.