Imperial College London
Alternate

Dr Paul F. McKay

Faculty of Medicine, Department of Infectious Disease

Advanced Research Fellow
 
 
 
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Contact

 

+44 (0)20 7594 2542p.mckay

 
 
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Location

 

125 (Shattock Group)Wright Fleming WingSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{McKay:2017:10.1016/j.jconrel.2017.01.018,
author = {McKay, PF and Mann, JFS and Pattani, A and Kett, V and Aldon, Y and King, D and Malcolm, RK and Shattock, R},
doi = {10.1016/j.jconrel.2017.01.018},
journal = {Journal of Controlled Release},
pages = {74--83},
title = {Intravaginal immunisation using a novel antigen-releasing ring device elicits robust vaccine antigen-specific systemic and mucosal humoral immune responses},
url = {http://dx.doi.org/10.1016/j.jconrel.2017.01.018},
volume = {249},
year = {2017}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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 (167 μg) ± R848 (167 μg) 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 100 μg CN54gp140 + 200 μg 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-specifi
AU  - McKay,PF
AU  - Mann,JFS
AU  - Pattani,A
AU  - Kett,V
AU  - Aldon,Y
AU  - King,D
AU  - Malcolm,RK
AU  - Shattock,R
DO  - 10.1016/j.jconrel.2017.01.018
EP  - 83
PY  - 2017///
SN  - 1873-4995
SP  - 74
TI  - Intravaginal immunisation using a novel antigen-releasing ring device elicits robust vaccine antigen-specific systemic and mucosal humoral immune responses
T2  - Journal of Controlled Release
UR  - http://dx.doi.org/10.1016/j.jconrel.2017.01.018
UR  - http://hdl.handle.net/10044/1/43942
VL  - 249
ER  -
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