A synthetic human cytomegalovirus pp65-IE1 fusion antigen efficiently induces and expands virus specific T cells.

Autor: Link EK; Institute for Infectious Diseases and Zoonoses, Ludwig-Maximilians-Universität München, Veterinärstr. 13, 80539 Munich, Germany; German Center for Infection Research (DZIF), Germany., Brandmüller C; Institute for Infectious Diseases and Zoonoses, Ludwig-Maximilians-Universität München, Veterinärstr. 13, 80539 Munich, Germany; German Center for Infection Research (DZIF), Germany., Suezer Y; Paul-Ehrlich-Institut, Federal Institute for Vaccines and Biomedicines, Paul-Ehrlich-Straße 51-59, 63225 Langen, Germany; German Center for Infection Research (DZIF), Germany., Ameres S; Helmholtz Zentrum München, Research Unit Gene Vectors, Marchioninistraße 25, 81377 Munich, Germany; German Center for Infection Research (DZIF), Germany., Volz A; Institute for Infectious Diseases and Zoonoses, Ludwig-Maximilians-Universität München, Veterinärstr. 13, 80539 Munich, Germany; German Center for Infection Research (DZIF), Germany., Moosmann A; Helmholtz Zentrum München, Research Unit Gene Vectors, Marchioninistraße 25, 81377 Munich, Germany; German Center for Infection Research (DZIF), Germany., Sutter G; Institute for Infectious Diseases and Zoonoses, Ludwig-Maximilians-Universität München, Veterinärstr. 13, 80539 Munich, Germany; German Center for Infection Research (DZIF), Germany. Electronic address: Gerd.Sutter@lmu.de., Lehmann MH; Institute for Infectious Diseases and Zoonoses, Ludwig-Maximilians-Universität München, Veterinärstr. 13, 80539 Munich, Germany; German Center for Infection Research (DZIF), Germany. Electronic address: Michael.Lehmann@lmu.de.
Jazyk: angličtina
Zdroj: Vaccine [Vaccine] 2017 Sep 12; Vol. 35 (38), pp. 5131-5139. Date of Electronic Publication: 2017 Aug 14.
DOI: 10.1016/j.vaccine.2017.08.019
Abstrakt: Infection with human cytomegalovirus (HCMV) can cause severe complications in newborns and immunocompromised patients, and a prophylactic or therapeutic vaccine against HCMV is not available. Here, we generated a HCMV vaccine candidate fulfilling the regulatory requirements for GMP-compliant production and clinical testing. A novel synthetic fusion gene consisting of the coding sequences of HCMV pp65 and IE1 having a deleted nuclear localization sequence and STAT2 binding domain was introduced into the genome of the attenuated vaccinia virus strain MVA. This recombinant MVA, MVA-syn65_IE1, allowed for the production of a stable ∼120kDa syn65_IE1 fusion protein upon tissue culture infection. MVA-syn65_IE1 infected CD40-activated B cells activated and expanded pp65- and IE1-specific T cells derived from HCMV-seropositive donors to at least equal levels as control recombinant MVA expressing single genes for pp65 or IE1. Additionally, we show that MVA-syn65_IE1 induced HCMV pp65- and IE1-epitope specific T cells in HLA-A2.1-/HLA-DR1-transgenic H-2 class I-/class II-knockout mice. Thus, MVA-syn65_IE1 represents a promising vaccine candidate against HCMV and constitutes a basis for the generation of a multivalent vaccine targeting relevant pathogens in immunocompromised patients.
(Copyright © 2017 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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