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Vaccination with DNA plasmids expressing Gn coupled to C3d or alphavirus replicons expressing Gn protects mice against rift valley fever virus

Bhardwaj, N and Heise, MT and Ross, TM (2010) Vaccination with DNA plasmids expressing Gn coupled to C3d or alphavirus replicons expressing Gn protects mice against rift valley fever virus. PLoS Neglected Tropical Diseases, 4 (6).

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Abstract

Background: Rift Valley fever (RVF) is an arthropod-borne viral zoonosis. Rift Valley fever virus (RVFV) is an important biological threat with the potential to spread to new susceptible areas. In addition, it is a potential biowarfare agent. Methodology/Principal Findings: We developed two potential vaccines, DNA plasmids and alphavirus replicons, expressing the Gn glycoprotein of RVFV alone or fused to three copies of complement protein, C3d. Each vaccine was administered to mice in an all DNA, all replicon, or a DNA prime/replicon boost strategy and both the humoral and cellular responses were assessed. DNA plasmids expressing Gn-C3d and alphavirus replicons expressing Gn elicited high titer neutralizing antibodies that were similar to titers elicited by the live-attenuated MP12 virus. Mice vaccinated with an inactivated form of MP12 did elicit high titer antibodies, but these antibodies were unable to neutralize RVFV infection. However, only vaccine strategies incorporating alphavirus replicons elicited cellular responses to Gn. Both vaccines strategies completely prevented weight loss and morbidity and protected against lethal RVFV challenge. Passive transfer of antisera from vaccinated mice into naïve mice showed that both DNA plasmids expressing Gn-C3d and alphavirus replicons expressing Gn elicited antibodies that protected mice as well as sera from mice immunized with MP12. Conclusion/Significance: These results show that both DNA plasmids expressing Gn-C3d and alphavirus replicons expressing Gn administered alone or in a DNA prime/replicon boost strategy are effective RVFV vaccines. These vaccine strategies provide safer alternatives to using live-attenuated RVFV vaccines for human use. © 2010 Bhardwaj et al.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Bhardwaj, N
Heise, MT
Ross, TM
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorBausch, Daniel G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Centers: Other Centers, Institutes, Offices, or Units > Center for Vaccine Research
Date: 1 June 2010
Date Type: Publication
Journal or Publication Title: PLoS Neglected Tropical Diseases
Volume: 4
Number: 6
DOI or Unique Handle: 10.1371/journal.pntd.0000725
Schools and Programs: Graduate School of Public Health > Infectious Diseases and Microbiology
Refereed: Yes
MeSH Headings: Alphavirus--genetics; Alphavirus--immunology; Analysis of Variance; Animals; Antibodies, Neutralizing--blood; Antibodies, Viral--blood; Cell Line; Complement C3d--genetics; Complement C3d--immunology; Enzyme-Linked Immunosorbent Assay; Female; Humans; Immunization, Passive; Immunoglobulin Isotypes--blood; Mice; Mice, Inbred BALB C; Peptides--chemistry; Peptides--immunology; Plasmids; Rift Valley Fever--immunology; Rift Valley Fever--prevention & control; Rift Valley fever virus--genetics; Rift Valley fever virus--immunology; Vaccines, DNA--genetics; Vaccines, DNA--immunology; Vaccines, DNA--pharmacology; Viral Envelope Proteins--genetics; Viral Envelope Proteins--immunology; Weight Loss
Other ID: NLM PMC2889828
PubMed Central ID: PMC2889828
PubMed ID: 20582312
Date Deposited: 03 Aug 2012 21:00
Last Modified: 02 Feb 2019 16:57
URI: http://d-scholarship.pitt.edu/id/eprint/13382

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