Mixing of M segment DNA vaccines to Hantaan virus and Puumala virus reduces their immunogenicity in hamsters

Spik, Kristin; Badger, Catherine V.; Mathiessen, Iacob; Tjelle, Torunn Elisabeth; Hooper, Jay W.; Schmaljohn, Connie S.

doi:10.1016/j.vaccine.2008.03.097

Cited by 29 publications

(23 citation statements)

References 18 publications

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“…The results of studies performed in our laboratory and by others have demonstrated that i.m. EP is a highly effective method for facilitating the uptake and expression of DNA vaccines in multiple animal species (27)(28)(29)44). In addition, i.m.…”

Section: Resultsmentioning

confidence: 99%

A DNA Vaccine for Venezuelan Equine Encephalitis Virus Delivered by Intramuscular Electroporation Elicits High Levels of Neutralizing Antibodies in Multiple Animal Models and Provides Protective Immunity to Mice and Nonhuman Primates

Dupuy

Richards

Ellefsen

et al. 2011

Clin. Vaccine Immunol.

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We evaluated the immunogenicity and protective efficacy of a DNA vaccine expressing codon-optimized envelope glycoprotein genes of Venezuelan equine encephalitis virus (VEEV) when delivered by intramuscular electroporation. Mice vaccinated with the DNA vaccine developed robust VEEV-neutralizing antibody responses that were comparable to those observed after administration of the live-attenuated VEEV vaccine TC-83 and were completely protected from a lethal aerosol VEEV challenge. The DNA vaccine also elicited strong neutralizing antibody responses in rabbits that persisted at high levels for at least 6 months and could be boosted by a single additional electroporation administration of the DNA performed approximately 6 months after the initial vaccinations. Cynomolgus macaques that received the vaccine by intramuscular electroporation developed substantial neutralizing antibody responses and after an aerosol challenge had no detectable serum viremia and had reduced febrile reactions, lymphopenia, and clinical signs of disease compared to those of negative-control macaques. Taken together, our results demonstrate that this DNA vaccine provides a potent means of protecting against VEEV infections and represents an attractive candidate for further development.Venezuelan equine encephalitis virus (VEEV) is a nonsegmented, positive-sense RNA virus of the genus Alphavirus in the family Togaviridae (17). Naturally transmitted by mosquitoes through rodent hosts, VEEV is highly pathogenic for equines and humans and has sporadically caused widespread epidemics in North, Central, and South America (48). While most equine and human outbreaks have been caused by the epizootic IAB and IC subtypes of VEEV, isolated cases of disease caused in equines and humans by infection with the enzootic ID and IE subtypes have also been reported (10,32,50). Regardless of the variety, human infection with VEEV typically results in an acute, incapacitating, but self-limiting disease characterized by fever, headache, lymphopenia, myalgia, and malaise (3). Severe neurological disease, including fatal encephalitis, can also result from VEEV infection of humans, although the case fatality rate is estimated to be low (Յ1%) (45). However, numerous documented laboratory accidents and the results of animal studies have demonstrated that VEEV is also highly infectious in aerosols, and infection with aerosolized VEEV could potentially result in higher mortality than that observed with natural infection (15,18,26). In addition to producing incapacitating or lethal infections and being infectious in aerosols, VEEV is also easily grown to high titers in inexpensive and unsophisticated cell culture systems and is relatively stable (45). As a result, VEEV represents a significant potential biological defense threat and is classified as a category B priority biodefense agent by both the Centers for Disease Control and Prevention and the National Institute of Allergy and Infectious Diseases.There are no licensed human vaccines for VEEV. While live-attenuated...

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Section: Resultsmentioning

confidence: 99%

A DNA Vaccine for Venezuelan Equine Encephalitis Virus Delivered by Intramuscular Electroporation Elicits High Levels of Neutralizing Antibodies in Multiple Animal Models and Provides Protective Immunity to Mice and Nonhuman Primates

Dupuy

Richards

Ellefsen

et al. 2011

Clin. Vaccine Immunol.

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“…This would reduce the burden of developing specific vaccines for the myriad different pathogenic hantaviruses around the world. Combinations of plasmids co-delivered separately or delivered as mixtures shows promise in animal models [15,32]. Data from these studies have demonstrated that DNA vaccines can also elicit cross-protection against other species of hantaviruses [13,14].…”

Section: Discussionmentioning

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

Self Cite

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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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“…[172]). Apart from that, only two molecular vaccines against HFRS have been tested in humans, the first was recombinant vaccinia-vectored vaccine expressing the M segment of HTNV [173] and the second plasmid DNA [174]. The advantage of DNA vaccines is that they offer an easy way to construct multivalent vaccines and they are able to induce long-lasting humoral and cellular immunity.…”

Section: Preventionmentioning

confidence: 99%

Hantavirus infections

Avšič-Županc

Saksida

Korva

2019

Clinical Microbiology and Infection

269

321

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Over the past few decades understanding and recognition of hantavirus infection has greatly improved worldwide, but both the amplitude and the magnitude of hantavirus outbreaks have been increasing. Several novel hantaviruses with unknown pathogenic potential have been identified in a variety of insectivore hosts. With the new hosts, new geographical distributions of hantaviruses have also been discovered and several new species were found in Africa. Hantavirus infection in humans can result in two clinical syndromes: haemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS) caused by Old World and New World hantaviruses, respectively. The clinical presentation of HFRS varies from subclinical, mild, and moderate to severe, depending in part on the causative agent of the disease. In general, HFRS caused by Hantaan virus, Amur virus and Dobrava virus are more severe with mortality rates from 5 to 15%, whereas Seoul virus causes moderate and Puumala virus and Saaremaa virus cause mild forms of disease with mortality rates <1%. The central phenomena behind the pathogenesis of both HFRS and HCPS are increased vascular permeability and acute thrombocytopenia. The pathogenesis is likely to be a complex multifactorial process that includes contributions from immune responses, platelet dysfunction and the deregulation of endothelial cell barrier functions. Also a genetic predisposition, related to HLA type, seems to be important for the severity of the disease. As there is no effective treatment or vaccine approved for use in the USA and Europe, public awareness and precautionary measures are the only ways to minimize the risk of hantavirus disease.

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Mixing of M segment DNA vaccines to Hantaan virus and Puumala virus reduces their immunogenicity in hamsters

Cited by 29 publications

References 18 publications

A DNA Vaccine for Venezuelan Equine Encephalitis Virus Delivered by Intramuscular Electroporation Elicits High Levels of Neutralizing Antibodies in Multiple Animal Models and Provides Protective Immunity to Mice and Nonhuman Primates

A DNA Vaccine for Venezuelan Equine Encephalitis Virus Delivered by Intramuscular Electroporation Elicits High Levels of Neutralizing Antibodies in Multiple Animal Models and Provides Protective Immunity to Mice and Nonhuman Primates

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 infections

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