[Immune effects of four coxsackievirus B3 VP1 DNA fusion vaccines in mice]
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Evaluation of Zika Virus-specific T-cell Responses in Immunoprivileged Organs of Infected Ifnar1-/- Mice
Published on: October 17, 2018
Gui-xia Liu1, Jia-ming Lan, Xia Chuai
1Department of Pathogenic Biology, Hebei Medical University, Shijiazhuang, China. lguixia@hotmail.com
Aim:
To compare the immunogenicity and protective effects on CVB3 infected mice of four DNA fusion vaccines coupling coxsackievirus B3 (CVB3) VP1 with macrophage-derived chemokine (MDC), C3d3, shiga toxin B subuit (STxB) and mouse beta-defensin-2 (mBD2), respectively.
Methods:
BALB/c mice were divided into 6 groups randomly and inoculated in quadriceps at 3-week interval for 3 times with pcDNA3, pcDNA3/VP1, pcDNA3/MDC-VP1, pcDNA3/VP1-C3d3, pcDNA3/STxB-VP1 and pcDNA3/mBD2 -VP1, respectively. Fourteen days after every inoculation, serum samples were collected and CVB3 specific neutralizing antibodies were determined. Three weeks after the last immunization, the mice were treated in three ways. First, the spleen cells were isolated from 3 mice of each group and specific CTL activities were tested. Second, 3 mice of each group were further challenged with 3LDLD(50); CVB3 and sacrificed 7 days later, and their blood viral titers were evaluated. Third, the rest mice of each group were subjected to intraperitoneal (i.p.) challenge with 5LDLD(50); CVB3 and their survival was observed.
Results:
The neutralizing antibodies against CVB3 were induced in pcDNA3/VP1, pcDNA3/MDC-VP1, pcDNA3/VP1-C3d3, pcDNA3/STxB-VP1 and pcDNA3/mBD2 -VP1 groups, and antibody titers correlated with the number of injections (P<0.01). After three immunizations, the antibody titers in pcDNA3/MDC-VP1, pcDNA3/VP1-C3d3 and pcDNA3/mBD2 -VP1 groups were higher than the ones in pcDNA3/VP1and pcDNA3/STxB-VP1 groups (P<0.01). The specific CTL activities in both pcDNA3/STxB-VP1 and pcDNA3/mBD2-VP1 groups were significantly stronger than those in the other groups (P<0.01). After CVB3 challenge, the blood viral titers in the pcDNA3/MDC-VP1, pcDNA3/VP1-C3d3 and pcDNA3/mBD2-VP1 groups were lower than those in the other groups (P<0.01), and the pcDNA3/MDC-VP1 and pcDNA3/VP1-C3d3 mice survived longer than the others (P<0.05).
Conclusion:
Both pcDNA3/MDC-VP1 and pcDNA3/VP1-C3d3 vaccines could induce stronger immune responses, resulting in higher survival rates and better protective effects on CVB3 infection than pcDNA3/STxB-VP1, pcDNA3/mBD2-VP1 and pcDNA3/VP1 vaccines.
Insights
New DNA fusion vaccines combining coxsackievirus B3 (CVB3) VP1 with MDC or C3d3 enhanced immunogenicity. These vaccines offered superior protection against CVB3 infection in mice compared to other constructs.
Area of Science:
- Virology
- Immunology
- Vaccine Development
Context:
- Coxsackievirus B3 (CVB3) is a significant human pathogen.
- Developing effective vaccines against viral infections is crucial.
- DNA fusion vaccines offer a promising platform for inducing immune responses.
Purpose:
- To evaluate the immunogenicity and protective efficacy of four novel DNA fusion vaccines against CVB3.
- To compare vaccines coupling CVB3 VP1 with macrophage-derived chemokine (MDC), C3d3, shiga toxin B subunit (STxB), and mouse beta-defensin-2 (mBD2).
Summary:
- BALB/c mice were immunized with different DNA constructs, including pcDNA3/MDC-VP1 and pcDNA3/VP1-C3d3.
- Mice vaccinated with pcDNA3/MDC-VP1 and pcDNA3/VP1-C3d3 exhibited higher neutralizing antibody titers and stronger CTL activities.
- These two vaccine groups also showed reduced viral loads and improved survival rates following CVB3 challenge.
Impact:
- The study identifies pcDNA3/MDC-VP1 and pcDNA3/VP1-C3d3 as highly effective vaccine candidates against CVB3.
- Findings contribute to the understanding of DNA vaccine design for viral hemorrhagic fever and myocarditis.
- This research paves the way for potential clinical applications in preventing CVB3-related diseases.
