Construction and Nonclinical Testing of a Puumala Virus Synthetic M Gene-Based DNA Vaccine

Brocato, Rebecca L.; Josleyn, M. J.; Wahl‐Jensen, Victoria; Schmaljohn, Connie S.; Hooper, Jay W.

doi:10.1128/cvi.00546-12

Cited by 36 publications

(54 citation statements)

References 42 publications

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“…This plasmid has been submitted to the ATCC, Patent Deposit Designation PTA-11660. The HTNV M gene DNA vaccine plasmid is designated as pWRG/HTN-M( x ), the PUUV vaccine plasmid is pWRG/PUU-M(s2), and the ANDV is pWRG/AND-M, they have been described previously [13,14]. …”

Section: Methodsmentioning

confidence: 99%

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A novel Sin Nombre virus DNA vaccine and its inclusion in a candidate pan-hantavirus vaccine against hantavirus pulmonary syndrome (HPS) and hemorrhagic fever with renal syndrome (HFRS)

Hooper

Josleyn

Ballantyne

et al. 2013

Vaccine

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Sin Nombre virus (SNV; family Bunyaviridae, genus Hantavirus) causes a hemorrhagic fever known as hantavirus pulmonary syndrome (HPS) in North America. There have been approximately 200 fatal cases of HPS in the United States since 1993, predominantly in healthy working-age males (case fatality rate 35%). There are no FDA-approved vaccines or drugs to prevent or treat HPS. Previously, we reported that hantavirus vaccines based on the full-length M gene segment of Andes virus (ANDV) for HPS in South America, and Hantaan virus (HTNV) and Puumala virus (PUUV) for hemorrhagic fever with renal syndrome (HFRS) in Eurasia, all elicited high-titer neutralizing antibodies in animal models. HFRS is more prevalent than HPS (>20,000 cases per year) but less pathogenic (case fatality rate 1–15%). Here, we report the construction and testing of a SNV full-length M gene-based DNA vaccine to prevent HPS. Rabbits vaccinated with the SNV DNA vaccine by muscle electroporation (mEP) developed high titers of neutralizing antibodies. Furthermore, hamsters vaccinated three times with the SNV DNA vaccine using a gene gun were completely protected against SNV infection. This is the first vaccine of any kind that specifically elicits high-titer neutralizing antibodies against SNV. To test the possibility of producing a pan-hantavirus vaccine, rabbits were vaccinated by mEP with an HPS mix (ANDV and SNV plasmids), or HFRS mix (HTNV and PUUV plasmids), or HPS/HFRS mix (all four plasmids). The HPS mix and HFRS mix elicited neutralizing antibodies predominantly against ANDV/SNV and HTNV/PUUV, respectively. Furthermore, the HPS/HFRS mix elicited neutralizing antibodies against all four viruses. These findings demonstrate a pan-hantavirus vaccine using a mixed-plasmid DNA vaccine approach is feasible and warrants further development.

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Section: Methodsmentioning

confidence: 99%

“…Vaccinations using an XR particle-mediated epidermal delivery device (gene gun) (PowderJect-XR delivery device; PowderJect Vaccines, Inc.) have been described previously [13,14,25]. Anesthetized outbred female Syrian hamsters (6–8 weeks or older) were vaccinated with four administrations per vaccination.…”

Section: Methodsmentioning

confidence: 99%

A novel Sin Nombre virus DNA vaccine and its inclusion in a candidate pan-hantavirus vaccine against hantavirus pulmonary syndrome (HPS) and hemorrhagic fever with renal syndrome (HFRS)

Hooper

Josleyn

Ballantyne

et al. 2013

Vaccine

View full text Add to dashboard Cite

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“…To test whether the release of ANDV glycopro- teins was a particular property of ANDV or if it was a more general feature of hantaviruses, plasmid-driven expression of PUUV glycoproteins was next tested. To this end, 293FT cells were transfected with 8 g of the plasmid pWRG/PUU-M(s2) coding for PUUV-GPC under the cytomegalovirus promoter (32). When cell lysates and the concentrated supernatant of pWRG/PUU-M(s2)-transfected cells were analyzed by Western blotting, PUUV Gc was detected in both fractions with its expected molecular mass (Fig.…”

mentioning

confidence: 99%

Hantavirus Gn and Gc Glycoproteins Self-Assemble into Virus-Like Particles

Acuña

Cifuentes-Muñoz

Márquez

et al. 2014

J Virol

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f How hantaviruses assemble and exit infected cells remains largely unknown. Here, we show that the expression of Andes (ANDV) and Puumala (PUUV) hantavirus Gn and Gc envelope glycoproteins lead to their self-assembly into virus-like particles (VLPs) which were released to cell supernatants. The viral nucleoprotein was not required for particle formation. Further, a Gc endodomain deletion mutant did not abrogate VLP formation. The VLPs were pleomorphic, exposed protrusions and reacted with patient sera.

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“…For both the hantavirus and VEEV DNA vaccines, gene optimization was found to increase expression and to improve antibody responses in animals and humans. 28,[30][31][32][33][34][35] For the 2 hantavirus vaccines, optimization also mitigated immune interference, which we observed when using non-optimized constructs. 27,29 Although we did not have nonoptimized constructs for the SUDV or RAVV DNA vaccines, we Figure 6.…”

Section: Discussionmentioning

confidence: 93%

Codon-optimized filovirus DNA vaccines delivered by intramuscular electroporation protect cynomolgus macaques from lethal Ebola and Marburg virus challenges

Grant-Klein

Altamura

Badger

et al. 2015

Human Vaccines & Immunotherapeutics

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Cynomolgus macaques were vaccinated by intramuscular electroporation with DNA plasmids expressing codonoptimized glycoprotein (GP) genes of Ebola virus (EBOV) or Marburg virus (MARV) or a combination of codon-optimized GP DNA vaccines for EBOV, MARV, Sudan virus and Ravn virus. When measured by ELISA, the individual vaccines elicited slightly higher IgG responses to EBOV or MARV than did the combination vaccines. No significant differences in immune responses of macaques given the individual or combination vaccines were measured by pseudovirion neutralization or IFN-g ELISpot assays. Both the MARV and mixed vaccines were able to protect macaques from lethal MARV challenge (5/6 vs. 6/6). In contrast, a greater proportion of macaques vaccinated with the EBOV vaccine survived lethal EBOV challenge in comparison to those that received the mixed vaccine (5/6 vs. 1/6). EBOV challenge survivors had significantly higher pre-challenge neutralizing antibody titers than those that succumbed.

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Construction and Nonclinical Testing of a Puumala Virus Synthetic M Gene-Based DNA Vaccine

Cited by 36 publications

References 42 publications

A novel Sin Nombre virus DNA vaccine and its inclusion in a candidate pan-hantavirus vaccine against hantavirus pulmonary syndrome (HPS) and hemorrhagic fever with renal syndrome (HFRS)

A novel Sin Nombre virus DNA vaccine and its inclusion in a candidate pan-hantavirus vaccine against hantavirus pulmonary syndrome (HPS) and hemorrhagic fever with renal syndrome (HFRS)

Hantavirus Gn and Gc Glycoproteins Self-Assemble into Virus-Like Particles

Codon-optimized filovirus DNA vaccines delivered by intramuscular electroporation protect cynomolgus macaques from lethal Ebola and Marburg virus challenges

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