Open Access Research article

An adjuvanted inactivated murine cytomegalovirus (MCMV) vaccine induces potent and long-term protective immunity against a lethal challenge with virulent MCMV

Huadong Wang14, Yanfeng Yao1, Chaoyang Huang2, Xingxing Fu3, Quanjiao Chen1, Hongbo Zhang1, Jianjun Chen1, Fang Fang2, Zhenyuan Xie5 and Ze Chen123*

Author Affiliations

1 State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, Hubei, China

2 College of Life Science, Hunan Normal University, Changsha 410081, Hunan, China

3 Shanghai Institute of Biological Products, Shanghai 200052, China

4 Graduate University of Chinese Academy of Sciences, Beijing 100049, China

5 Xie Tu Community Medical Service Center, Xuhui, District of Shanghai, China

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BMC Infectious Diseases 2014, 14:195  doi:10.1186/1471-2334-14-195

Published: 11 April 2014

Abstract

Background

Human cytomegalovirus (HCMV) is a ubiquitous pathogen that causes serious problems in immunocompromised or immunologically immature hosts. Vaccination is the preferred approach for prevention of HCMV infection, but so far no approved HCMV vaccine is available. In this study, we assessed the immunogenicity and protective immunity of a formalin-inactivated murine cytomegalovirus vaccine (FI-MCMV) in a mouse model in combination with adjuvants MF59, alum, or chitosan.

Methods

Specific-pathogen-free BALB/c mice aged 6–8 weeks were immunized twice, 3 weeks apart, with various doses of FI-MCMV (0.25 μg, 1 μg, 4 μg) with or without adjuvant. Mice were challenged with a lethal dose (5 × LD50) of a more virulent mouse salivary gland-passaged MCMV 3 weeks after the second immunization. The protective immunity of the vaccine was evaluated by determining the survival rates, residual spleen and salivary gland viral loads, body weight changes, and serum anti-MCMV IgG titers.

Results

Immunization with FI-MCMV vaccine induced a high level of specific antibody response. Antigen sparing was achieved by the addition of an adjuvant, which significantly enhanced the humoral response to vaccine antigens with a wide range of doses. The level of live virus detected in the spleen on day 5 and in the salivary glands on day 21 after the lethal challenge was significantly lower in adjuvant-treated groups than in controls. Survival rates in adjuvant-treated groups also increased significantly. Furthermore, these protective immune responses were sustained for at least 6 months following immunization.

Conclusions

These results show that inactivated MCMV vaccine is effective, and that the adjuvanted FI-MCMV vaccine provides more effective and longer-term protection than the adjuvant-free vaccine.

Keywords:
Cytomegalovirus; Inactivated vaccine; Adjuvant; Long-term protective immunity