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Med Microbiol Immunol (2008) 197:117123 DOI 10.1007/s00430-008-0074-5
ORIGINAL INVESTIGATION
Evaluation of recombinant modiWed vaccinia Ankara virus-based rhesus cytomegalovirus vaccines in rhesus macaques
Yujuan Yue Zhongde Wang Kristina Abel Jinliang Li Lisa Strelow Angelo Mandarino Meghan K. Eberhardt Kimberli A. Schmidt
Don J. Diamond Peter A. Barry
Received: 23 October 2007 / Published online: 15 January 2008 Springer-Verlag 2008
Abstract A vaccine consisting of rhesus cytomegalovirus (RhCMV) pp65-2, gB and IE1 expressed via modiWed vaccinia Ankara (MVA) was evaluated in rhesus macaques with or without prior priming with expression plasmids for the same antigens. Following two MVA treatments, comparable levels of anti-gB, pp65-2 and neutralizing antibody responses, and pp65-2- and IE1-speciWc cellular immune responses were detected in both vaccinated groups. Similar reductions in plasma peak viral loads were observed in these groups compared to untreated controls. This study demonstrates the immunogenicity and protective eYcacy of rMVA-based RhCMV subunit vaccines in a primate host
and warrants further investigation to improve the eYcacy of subunit vaccines against CMV.
Keywords Cytomegalovirus vaccine Rhesus macaques ModiWed vaccinia Ankara virus
Introduction
Development of an eVective vaccine for human cytomegalovirus (HCMV) has been designated a level 1 priority by the Institute of Medicine because of the devastating impact of congenital infection by HCMV which can have lifelong consequences [19]. The strict species-speciWcity of the virus requires assessment of vaccine strategies in a cognate animal model. Rhesus CMV (RhCMV) infection of rhesus macaques (Macaca mulattaMmu) strongly recapitulates HCMV infection in humans in terms of the similarity of viral genome, persistence, pathogenesis and host immune responses [24, 26, 27], therefore, it represents a clinically relevant model to evaluate HCMV vaccine strategies.
Measurement of natural immunity to HCMV supports targeting the predominant neutralizing antibody response antigen gB and the strongly recognized cellular immunogens pp65 and IE1 as the optimal antigens in a vaccine formulated to prevent infection and control disease [28]. Previously, a study in Mmu demonstrated that immunization with DNA vaccines expressing RhCMV pp65-2 and truncated gB with deletion of transmembrane and intracellular domains (gB[afii9797]) stimulated antigen-speciWc CD8+ T cell and antibody responses and provided limited protection against challenge [25]. A notable observation of this study was that a combination of DNA priming administered Wve times in 50 weeks followed by a heterologous boost...