Oral administration of an adenovirus vector encoding both an avian influenza A hemagglutinin and a TLR3 ligand induces antigen specific granzyme B and IFN-γ T cell responses in humans

Peters, Wendy; Brandl, Jennifer R.; Lindbloom, Jonathan D.; Martínez, Carlos; Scallan, Ciaran D.; Trager, George R.; Tingley, Debora W.; Kabongo, Martin L.; Tucker, Sean N.

doi:10.1016/j.vaccine.2013.01.023

Cited by 64 publications

(60 citation statements)

References 22 publications

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“…It is suggested that some capsules and tablets can be designed to enhance the stability of vaccines to environmental conditions such as high humidity and temperature, which may reduce the need for specific storage conditions and can greatly reduce the cost of implementing such a strategy in the field. Recently a tablet-based oral influenza vaccine was shown to elicit strong anti-viral antibody and cellular responses against avian flu antigens in humans [218]. This approach utilized a non-replicating adenovirus vector expressing avian flu antigens together with a TLR3 agonist [218].…”

Section: Tablets and Capsulesmentioning

confidence: 99%

“…Recently a tablet-based oral influenza vaccine was shown to elicit strong anti-viral antibody and cellular responses against avian flu antigens in humans [218]. This approach utilized a non-replicating adenovirus vector expressing avian flu antigens together with a TLR3 agonist [218]. This approach may be adaptable to an oral vaccine against adenoviral diarrheal infections, which have significant incidence in children, especially in developing countries [219].…”

Section: Tablets and Capsulesmentioning

confidence: 99%

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Delivery strategies to enhance oral vaccination against enteric infections

Davitt

Lavelle

2015

Advanced Drug Delivery Reviews

133

102

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Section: Tablets and Capsulesmentioning

confidence: 99%

Section: Tablets and Capsulesmentioning

confidence: 99%

Delivery strategies to enhance oral vaccination against enteric infections

Davitt

Lavelle

2015

Advanced Drug Delivery Reviews

133

102

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“…Granzymes are serine proteases that mediate caspase-cascade activation in virusinfected cells upon release from their effector cells, cytotoxic T cells and NK/NKT cells, and thus lead to the programmed cell death of their target [27]. The use of Granzyme B activity as a marker of cellmediated cytotoxicity has been evaluated before, and found to be specific, robust and in correlation with traditional measures of cytolytic activity [28,29]. In combination with antibody titers, Granzyme B activity levels were shown to predict vaccine efficacy in elderly populations [13,30].…”

Section: Discussionmentioning

confidence: 99%

Measurement of Cellular Immunity to Influenza Vaccination in Rheumatoid Arthritis; Comparison of Three Assays

Madar-Balakirski¹,

Arad²,

Sharon³

et al. 2015

J Vaccines Vaccin

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Objective:Monitoring of immune responses is essential in the care of immunosuppressed individuals, including rheumatic patients. Evaluation of cellular immunity is essential for confirming virus-specific effector cell functions, but it is poorly standardized, and suffers from technical limitations and inaccurate results. There is, therefore, a need for reliable techniques for assessing cell-mediated immunity. In this study we compared the cell-mediated immunity response to influenza vaccine between a population of Rheumatoid Arthritis (RA) patients and healthy subjects by three methods.Methods: Trivalent influenza subunit vaccine was administered to 18 RA patients who were taking diseasemodifying antirheumatic drugs and to 18 healthy controls. Peripheral Blood Mononuclear Cells (PBMCs) and sera were obtained immediately before and ~28 days after vaccination. Cell-mediated immunity responses to vaccination were evaluated by (1) flow cytometric analysis of IL-2/IFN-γ production in activated CD4/CD8 T-cells, (2) enzymelinked immunosorbent assay for the analysis of IFN-γ secretion, and (3) Granzyme B activity assay. Humoral response was evaluated by the hemagglutination inhibition assay. Results:Vaccination induced a significant increase in PBMC IFN-γ secretion and Granzyme B activity in the RA patients. Granzyme B activity also significantly increased in the controls, but there was no change in the levels of secreted IFN-γ. No group differences in the frequencies of IFN-γ/IL-2-producing activated CD4/CD8 T-cells were observed by flow cytometry. The geometric mean of hemagglutination inhibition antibody titers increased significantly for the H1N1/H3N2 influenza strains in both groups.Conclusions: Granzyme B activity assay was the only method to detect a significant cell-mediated immunity response in both groups while significant increase in IFN-γ secretion was demonstrated only in RA patients. Flow cytometric analysis failed to show IL-2 and IFN-γ production in both groups. Currently available methods for measuring cellular responsiveness to influenza vaccination are inconsistent and limited in their ability to reflect acquired cellular immunity.

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“…Результаты большинства исследований не представлены, од-нако в 2013 году Vaxart Inc. опубликовала резуль-таты клинических испытаний вакцины ND1.1, которая представляет собой вектор на основе Ad5, несущий ген гемагглютинина птичьего ви-руса гриппа H5, и адъювант dsRNA, действую-щий как лиганд для Toll-подобных рецепторов (TLR3). В этой работе впервые была продемон-стрирована иммуногенность вакцины при перо-ральном приеме в виде капсул [20]. Исследова-ние показало хорошую переносимость вакцины, у 73% испытуемых наблюдалась выработка IFNg, хотя Т-клеточный иммунный ответ был слабым.…”

Section: Development Of Vaccines Based On Adenoviral Vectors: a Revieunclassified

Development of Vaccines Based on Adenoviral Vectors: A Review of Foreign Clinical Studies (Part 2)

Черенова¹,

Каштиго²,

Саядян³

et al. 2017

Med. immunol.

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Адрес для переписки:Черенова Любовь Викторовна ФГБУ «Федеральный научно-исследовательский центр эпидемиологии и микробиологии им. почетного академика Н.Ф. Гамалеи» Министерства здравоохранения РФ 123098, Россия, г. Москва, ул. Гамалеи, 18. Тел.: 8 (916) 329-92-78. Факс: 8 (499) 193-61-35. E-mail: cherenova@yandex.ru Address for correspondence : Cherenova Liubov V. N. Gamaleya Research Institute of Epidemiology and Microbiology 123098, Russian Federation, Moscow, Gamaleya str., 18. Phone: 7 (916) // Медицинская иммунология, 2017. Т. 19, № 4. С. 329-358. doi: 10.15789/1563-0625-2017-4-329-358 © Черенова Л.В. и соавт., 2017 /Meditsinskaya Immunologiya, 2017, Vol. 19, no. 4, pp. 329-358. doi: 10.15789/1563-0625-2017 Резюме. В настоящее время для многих инфекционных заболеваний человека не разработаны эффективные способы лечения и профилактики. Одним из последних достижений биотехнологии является использование аденовирусных векторов, несущих иммунодоминантные антигены различ-ных патогенов, в качестве генно-инженерных вакцин как профилактических, так и терапевтических. Использование генно-инженерных технологий позволяет не применять при производстве вакцин живые вирусы и бактерии, сокращает время разработки и получения новых вакцинных препаратов. Аденовирусные векторы естественным путем проникают в клетки человека, вызывая довольно дли-тельный и значительный как гуморальный, так и клеточный иммунный ответ. Во второй части об-зора мы планируем привести сведения о проводимых в настоящее время за рубежом клинических испытаниях вакцин на основе аденовирусных векторов против таких инфекционных заболеваний, как грипп, малярия, геморрагическая лихорадка Эбола, туберкулез, гепатит и ряда других. Будут рас-смотрены параметры отбора добровольцев, схемы и дозы, используемые при вакцинации, приведены результаты завершенных экспериментов и предварительные результаты незаконченных на данный момент исследований.

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Oral administration of an adenovirus vector encoding both an avian influenza A hemagglutinin and a TLR3 ligand induces antigen specific granzyme B and IFN-γ T cell responses in humans

Cited by 64 publications

References 22 publications

Delivery strategies to enhance oral vaccination against enteric infections

Delivery strategies to enhance oral vaccination against enteric infections

Measurement of Cellular Immunity to Influenza Vaccination in Rheumatoid Arthritis; Comparison of Three Assays

Development of Vaccines Based on Adenoviral Vectors: A Review of Foreign Clinical Studies (Part 2)

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