Human adenovirus serotype 5 vaccines : routes of delivery and formulations for successful immunization

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Title: Human adenovirus serotype 5 vaccines : routes of delivery and formulations for successful immunization
Author: Dekker, Joseph Dylan
Abstract: Delivery of medicinal products to specific targets can be aided by utilizing different routes of administration . Particular routes may be advantageous when delivering products designed for therapeutic drug delivery , gene therapy , or vaccination . Vaccine candidates must remain stable , be delivered to their proper compartments , and promote sufficient immune responses to their delivered antigens , properties that can be modulated by formulation , adjuvants , and alternate routes of administration . Recently , the nasal passageway has been recognized as a promising route , as mucosally delivered vaccines have the advantage of inducing protection at both mucosal surfaces , a common site of infection , and systemically . Human adenovirus serotype 5 (Ad5 ) is a candidate vaccine vector capable of being delivered through several routes and inducing strong immune responses to its delivered transgene . The studies presented include vaccination strategies following different routes of administration with various formulation components to determine the ability of Ad5 to deliver its transgene and induce immune responses . The first study screens formulation candidates’ effects on an Ad5 -based vaccine’s transduction in vitro , cellular and humoral immune responses in vivo , and efficacy upon challenge in mice . Screening formulation candidates in vitro can eliminate ineffective formulations , thereby limiting animal testing . An Ad5 -based Ebola virus vaccine delivered in a combination of mannitol , sucrose , and the surfactant , pluronic F68 , improves survival against lethal Ebola challenge in a mouse model compared to delivery in PBS alone . The second study tests the effect of an intravenously delivered Ad5 -based vaccine complexed with anti -Ad5 neutralizing antibodies on cellular and humoral immune responses . Different antibody ratios complexed to the Ad5 vector are able to induce disparate cellular and humoral responses . Ratios initiating a strong humoral response towards the Ad5 vector correlate with a reduction of the humoral response against the transgene and few transgene targeted effector T cells . Accordingly , ratios leading to minor humoral responses to the Ad5 vector resulted in stronger humoral responses to the transgene and a strong effector memory T cell response . Taken together , these studies provide insight on how to achieve necessary immune responses in vaccine protocols by testing routes of administration , formulations , and surface modifications of the Ad5 vector .
URI: http : / /hdl .handle .net /2152 /ETD -UT -2010 -08 -1669
Date: 2010-11-09

Citation

Human adenovirus serotype 5 vaccines : routes of delivery and formulations for successful immunization. Doctoral dissertation, University of Texas at Austin. Available electronically from http : / /hdl .handle .net /2152 /ETD -UT -2010 -08 -1669 .

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