Abstract
BackgroundHuman cytomegalovirus (HCMV) causes serious HCMV-related diseases in immunocompromised people. Vaccination is the most effective measure to control infection with the pathogen, yet no vaccine has been licensed till now. We performed a head-to-head comparison of the protective abilities of multiple DNA vaccines in murine model of murine cytomegalovirus (MCMV) infection.MethodsFive DNA vaccines were constructed. Four encoding MCMV proteins gp34 (m04), p65 (M84), DNA helicase (M105), and immediate-early 1 protein pp89 (IE-1) , respectively, which were reported to induce CD8+ T cell responses, were compared with the one expressing gB (M55), the neutralizing antibody target antigen, for immune protection in BALB/c mice. Mice were immunized with these DNA vaccines 1 to 4 times via intramuscular injection followed by electroporation, and were subsequently infected with a lethal dose (3 × LD50) of highly virulent SG-MCMV. Specific antibodies and IFN-γ secreting splenocytes were detected by immunoblotting and ELISPOT, respectively. Protective abilities in mice provided by the vaccines were evaluated by residual virus titers in organs, survival rate and weight loss.ResultsThese DNA vaccines, especially m04, M84 and IE-1, could effectively reduce the virus loads in salivary glands and spleens of mice, but they couldn’t completely clear the residual virus. Survival rates of 100% in mice after a lethal dose of MCMV infection could be reached by more than one dose of M84 vaccine or two doses of m04 or IE-1 vaccine. Immunization with M55 or M105 DNA at four doses offered mice only 62.5% survival rate after the lethal challenge.ConclusionsThe study demonstrated that DNA vaccines could effectively afford mice protection against infection with a highly virulent MCMV and that the protection offered by induced CD8+ T cell immunity might be superior to that by gB-specific antibodies. These results are valuable references for development and application of HCMV vaccines.
Highlights
Human cytomegalovirus (HCMV) causes serious HCMV-related diseases in immunocompromised people
Survival rates of mice against a lethal Salivary gland (SG)-murine cytomegalovirus (MCMV) infection To evaluate the protection provide by the five DNA vaccines, 420 female, 6 ~ 8 week old BALB/c mice were randomly divided into 21 groups, 20 mice each
The other 20 groups were immunized with m04, M84, M105, immediate-early 1 protein pp89 (IE-1) and M55 DNA vaccine at a dosage of 100 μg for 1 ~ 4 times, respectively, via intramuscular injection plus electroporation
Summary
Human cytomegalovirus (HCMV) causes serious HCMV-related diseases in immunocompromised people. Human cytomegalovirus (HCMV) is a common human herpesvirus, with infection rate of 40 ~ 90% in general population. It only causes clinical symptoms in people with a not-fully-developed or compromised immune system, such as newborns, organ transplant patients and has been identified as a high priority goal in biomedical research [4], yet no vaccine has been licensed till due to unsatisfactory results of clinical trials on the current HCMV vaccine candidates. Steininger reviewed these completed phase II clinical trials on HCMV vaccines [8]. Evaluation of ASP0113 (formerly TransVaxTM) is ongoing in phase III trials (NCT01877655 at www.clinicaltrials.gov)
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