دورية أكاديمية
أعرض في EDS

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

التفاصيل البيبلوغرافية
العنوان: Intravaginal immunisation using a novel antigen-releasing ring device elicits robust vaccine antigen-specific systemic and mucosal humoral immune responses.
المؤلفون: McKay PF; Imperial College London, Department of Medicine, Division of Infectious Diseases, Section of Virology, Norfolk Place, London W2 1PG, UK. Electronic address: p.mckay@imperial.ac.uk., Mann JF; Imperial College London, Department of Medicine, Division of Infectious Diseases, Section of Virology, Norfolk Place, London W2 1PG, UK., Pattani A; School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK., Kett V; School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK., Aldon Y; Imperial College London, Department of Medicine, Division of Infectious Diseases, Section of Virology, Norfolk Place, London W2 1PG, UK., King D; Imperial College London, Department of Medicine, Division of Infectious Diseases, Section of Virology, Norfolk Place, London W2 1PG, UK., Malcolm RK; School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK., Shattock RJ; Imperial College London, Department of Medicine, Division of Infectious Diseases, Section of Virology, Norfolk Place, London W2 1PG, UK.
المصدر: Journal of controlled release : official journal of the Controlled Release Society [J Control Release] 2017 Mar 10; Vol. 249, pp. 74-83. Date of Electronic Publication: 2017 Jan 21.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Elsevier Science Publishers Country of Publication: Netherlands NLM ID: 8607908 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-4995 (Electronic) Linking ISSN: 01683659 NLM ISO Abbreviation: J Control Release Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Amsterdam : Elsevier Science Publishers, 1984-
مواضيع طبية MeSH: Immunity, Mucosal*, AIDS Vaccines/*administration & dosage , Adjuvants, Immunologic/*administration & dosage , HIV Infections/*prevention & control , HIV-1/*immunology , Immunization/*instrumentation , env Gene Products, Human Immunodeficiency Virus/*administration & dosage, AIDS Vaccines/immunology ; Adjuvants, Immunologic/pharmacology ; Administration, Intravaginal ; Animals ; Antibody Formation ; Contraceptive Devices, Female ; Female ; HIV Infections/immunology ; Humans ; Imidazoles/administration & dosage ; Imidazoles/immunology ; Immunity, Humoral ; Immunoglobulin A/immunology ; Immunoglobulin G/immunology ; Sheep ; env Gene Products, Human Immunodeficiency Virus/immunology
مستخلص: The generation of effective levels of antigen-specific immunity at the mucosal sites of pathogen entry is a key goal for vaccinologists. We explored topical vaginal application as an approach to initiate local antigen-specific immunity, enhance previously existing systemic immunity or re-target responses to the mucosae. To deliver a protein vaccine formulation to the vaginal mucosal surface, we used a novel vaginal ring device comprising a silicone elastomer body into which three freeze-dried, rod-shaped, hydroxypropylmethylcellulose inserts were incorporated. Each rod contained recombinant HIV-1 CN54gp140 protein (167μg)±R848 (167μg) adjuvant. The inserts were loaded into cavities within each ring such that only the ends of the inserts were initially exposed. Sheep received a prime-boost vaccination regime comprising intramuscular injection of 100μg CN54gp140+200μg R848 followed by three successive ring applications of one week duration and separated by one month intervals. Other sheep received only the ring devices without intramuscular priming. Serum and vaginal mucosal fluids were sampled every two weeks and analysed by CN54gp140 ELISA and antigen-specific B cells were measured by flow cytometry at necropsy. Vaccine antigen-specific serum antibody responses were detected in both the intramuscularly-primed and vaginal mucosally-primed groups. Those animals that received only vaginal vaccinations had identical IgG but superior IgA responses. Analysis revealed that all animals exhibited mucosal antigen-specific IgG and IgA with the IgA responses 30-fold greater than systemic levels. Importantly, very high numbers of antigen-specific B cells were detected in local genital draining lymph nodes. We have elicited local genital antigen-specific immune responses after topical application of an adjuvanted antigen formulation within a novel vaginal ring vaccine release device. This regimen and delivery method elicited high levels of antigen-specific mucosal IgA and large numbers of local antigen-reactive B cells, both likely essential for effective mucosal protection.
(Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)
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معلومات مُعتمدة: G37872 United Kingdom Wellcome Trust
المشرفين على المادة: 0 (AIDS Vaccines)
0 (Adjuvants, Immunologic)
0 (Imidazoles)
0 (Immunoglobulin A)
0 (Immunoglobulin G)
0 (env Gene Products, Human Immunodeficiency Virus)
0 (gp140 envelope protein, Human immunodeficiency virus 1)
V3DMU7PVXF (resiquimod)
تواريخ الأحداث: Date Created: 20170125 Date Completed: 20171227 Latest Revision: 20181113
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC5333785
DOI: 10.1016/j.jconrel.2017.01.018
PMID: 28115243
قاعدة البيانات: MEDLINE
الوصف
تدمد:1873-4995
DOI:10.1016/j.jconrel.2017.01.018