Induction of pulmonary mucosal immune responses with a protein vaccine targeted to the DEC-205/CD205 receptor

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• 作者：Yoonkyung Do ; Arnaud M. Didierlaurent ; Seongho Ryu ; Hyein Koh ; Chae Gyu Park ; Steven Park ; David S. Perlin ; Bradford S. Powell ; Ralph M. Steinman
• 关键词：Y. pestis ; Yersinia pestis ; ICS ; intracellular cytokine staining ; poly IC (pIC) ; polyinosinic ; polycytidylic acid
• 刊名：Vaccine
• 出版年：2012
• 出版时间：5 October, 2012
• 年：2012
• 卷：30
• 期：45
• 页码：6359-6367
• 全文大小：1216 K

文摘

It is of great interest to develop a pneumonic plague vaccine that would induce combined humoral and cellular immunity in the lung. Here we investigate a novel approach based on targeting of dendritic cells using the DEC-205/CD205 receptor (DEC) via the intranasal route as way to improve mucosal cellular immunity to the vaccine. Intranasal administration of Yersinia pestis LcrV (V) protein fused to anti-DEC antibody together with poly IC as an adjuvant induced high frequencies of IFN-¦Ã secreting CD4<sup>+sup> T cells in the airway and lung as well as pulmonary IgG and IgA antibodies. Anti-DEC:LcrV was more efficient to induce IFN-¦Ã/TNF-¦Á/IL-2 secreting polyfunctional CD4<sup>+sup> T cells when compared to non-targeted soluble protein vaccine. In addition, the intranasal route of immunization with anti-DEC:LcrV was associated with improved survival upon pulmonary challenge with the virulent CO92 Y. pestis. Taken together, these data indicate that targeting dendritic cells via the mucosal route is a potential new avenue for the development of a mucosal vaccine against pneumonic plague.