An adjuvanted inactivated murine cytomegalovirus (MCMV) vaccine induces potent and long-term protective immunity against a lethal challenge with virulent MCMV.
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.
Huadong
H
Wang
Yanfeng
Y
Yao
Chaoyang
C
Huang
Xingxing
X
Fu
Quanjiao
Q
Chen
Hongbo
H
Zhang
Jianjun
J
Chen
Fang
F
Fang
Zhenyuan
Z
Xie
State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, Hubei, China. chenze2005@hotmail.com.
Ze
Z
Chen
D000276:Adjuvants, Immunologic; D000818:Animals; D022482:Cytomegalovirus Vaccines / Q000276:immunology*; D005260:Female; D006566:Herpesviridae Infections / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D018146:Muromegalovirus / Q000276:immunology*; D013047:Specific Pathogen-Free Organisms; D015164:Vaccines, Inactivated / Q000276:immunology; D019562:Viral Load
D000276:Adjuvants, Immunologic; D022482:Cytomegalovirus Vaccines; D015164:Vaccines, Inactivated