A Phase 1 clinical trial of a DNA vaccine for Venezuelan equine encephalitis delivered by intramuscular or intradermal electroporation
Venezuelan equine encephalitis virus (VEEV), a mosquito-borne alphavirus, causes periodic epizootics in equines and is a recognized biological defense threat for humans. There are currently no FDA-licensed vaccines against VEEV. We developed a candidate DNA vaccine expressing the E3-E2-6K-E1 genes o...
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| Published in | Vaccine Vol. 34; no. 31; pp. 3607 - 3612 |
|---|---|
| Main Authors | , , , |
| Format | Journal Article |
| Language | English |
| Published |
Netherlands
Elsevier Ltd
30.06.2016
Elsevier Limited |
| Subjects | |
| Online Access | Get full text |
| ISSN | 0264-410X 1873-2518 1873-2518 |
| DOI | 10.1016/j.vaccine.2016.04.077 |
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| Abstract | Venezuelan equine encephalitis virus (VEEV), a mosquito-borne alphavirus, causes periodic epizootics in equines and is a recognized biological defense threat for humans. There are currently no FDA-licensed vaccines against VEEV. We developed a candidate DNA vaccine expressing the E3-E2-6K-E1 genes of VEEV (pWRG/VEE) and performed a Phase 1 clinical study to assess the vaccine's safety, reactogenicity, tolerability, and immunogenicity when administered by intramuscular (IM) or intradermal (ID) electroporation (EP) using the Ichor Medical Systems TriGrid™ Delivery System. Subjects in IM-EP groups received 0.5mg (N=8) or 2.0mg (N=9) of pWRG/VEE or a saline placebo (N=4) in a 1.0ml injection. Subjects in ID-EP groups received 0.08mg (N=8) or 0.3mg (N=8) of DNA or a saline placebo (N=4) in a 0.15ml injection. Subjects were monitored for a total period of 360 days. No vaccine- or device-related serious adverse events were reported. Based on the results of a subject questionnaire, the IM- and ID-EP procedures were both considered to be generally acceptable for prophylactic vaccine administration, with the acute tolerability of ID EP delivery judged to be greater than that of IM-EP delivery. All subjects (100%) in the high and low dose IM-EP groups developed detectable VEEV-neutralizing antibodies after two or three administrations of pWRG/VEE, respectively. VEEV-neutralizing antibody responses were detected in seven of eight subjects (87.5%) in the high dose and five of eight subjects (62.5%) in the low dose ID-EP groups after three vaccine administrations. There was a correlation between the DNA dose and the magnitude of the resulting VEEV-neutralizing antibody responses for both IM and ID EP delivery. These results indicate that pWRG/VEE delivered by either IM- or ID-EP is safe, tolerable, and immunogenic in humans at the evaluated dose levels.
Clinicaltrials.gov registry number NCT01984983. |
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| AbstractList | Venezuelan equine encephalitis virus (VEEV), a mosquito-borne alphavirus, causes periodic epizootics in equines and is a recognized biological defense threat for humans. There are currently no FDA-licensed vaccines against VEEV. We developed a candidate DNA vaccine expressing the E3-E2-6K-E1 genes of VEEV (pWRG/VEE) and performed a Phase 1 clinical study to assess the vaccine's safety, reactogenicity, tolerability, and immunogenicity when administered by intramuscular (IM) or intradermal (ID) electroporation (EP) using the Ichor Medical Systems TriGrid™ Delivery System. Subjects in IM-EP groups received 0.5mg (N=8) or 2.0mg (N=9) of pWRG/VEE or a saline placebo (N=4) in a 1.0ml injection. Subjects in ID-EP groups received 0.08mg (N=8) or 0.3mg (N=8) of DNA or a saline placebo (N=4) in a 0.15ml injection. Subjects were monitored for a total period of 360 days. No vaccine- or device-related serious adverse events were reported. Based on the results of a subject questionnaire, the IM- and ID-EP procedures were both considered to be generally acceptable for prophylactic vaccine administration, with the acute tolerability of ID EP delivery judged to be greater than that of IM-EP delivery. All subjects (100%) in the high and low dose IM-EP groups developed detectable VEEV-neutralizing antibodies after two or three administrations of pWRG/VEE, respectively. VEEV-neutralizing antibody responses were detected in seven of eight subjects (87.5%) in the high dose and five of eight subjects (62.5%) in the low dose ID-EP groups after three vaccine administrations. There was a correlation between the DNA dose and the magnitude of the resulting VEEV-neutralizing antibody responses for both IM and ID EP delivery. These results indicate that pWRG/VEE delivered by either IM- or ID-EP is safe, tolerable, and immunogenic in humans at the evaluated dose levels.
Clinicaltrials.gov registry number NCT01984983. Abstract Venezuelan equine encephalitis virus (VEEV), a mosquito-borne alphavirus, causes periodic epizootics in equines and is a recognized biological defense threat for humans. There are currently no FDA-licensed vaccines against VEEV. We developed a candidate DNA vaccine expressing the E3-E2-6K-E1 genes of VEEV (pWRG/VEEV) and performed a Phase 1 clinical study to assess the vaccine's safety, reactogenicity, tolerability, and immunogenicity when administered by intramuscular (IM) or intradermal (ID) electroporation (EP) using the Ichor Medical Systems TriGrid™ Delivery System. Subjects in IM-EP groups received 0.5 mg ( N = 8) or 2.0 mg ( N = 9) of pWRG/VEE or a saline placebo ( N = 4) in a 1.0 ml injection. Subjects in ID-EP groups received 0.08 mg ( N = 8) or 0.3 mg ( N = 8) of DNA or a saline placebo ( N = 4) in a 0.15 ml injection. Subjects were monitored for a total period of 360 days. No vaccine- or device-related serious adverse events were reported. Based on the results of a subject questionnaire, the IM- and ID-EP procedures were both considered to be generally acceptable for prophylactic vaccine administration, with the acute tolerability of ID EP delivery judged to be greater than that of IM-EP delivery. All subjects (100%) in the high and low dose IM-EP groups developed detectable VEEV-neutralizing antibodies after two or three administrations of pWRG/VEE, respectively. VEEV-neutralizing antibody responses were detected in seven of eight subjects (87.5%) in the high dose and five of eight subjects (62.5%) in the low dose ID-EP groups after three vaccine administrations. There was a correlation between the DNA dose and the magnitude of the resulting VEEV-neutralizing antibody responses for both IM and ID EP delivery. These results indicate that pWRG/VEE delivered by either IM- or ID-EP is safe, tolerable, and immunogenic in humans at the evaluated dose levels. Clinicaltrials.gov registry number NCT01984983. Venezuelan equine encephalitis virus (VEEV), a mosquito-borne alphavirus, causes periodic epizootics in equines and is a recognized biological defense threat for humans. There are currently no FDA-licensed vaccines against VEEV. We developed a candidate DNA vaccine expressing the E3-E2-6K-E1 genes of VEEV (pWRG/VEE) and performed a Phase 1 clinical study to assess the vaccine's safety, reactogenicity, tolerability, and immunogenicity when administered by intramuscular (IM) or intradermal (ID) electroporation (EP) using the Ichor Medical Systems TriGrid(TM) Delivery System. Subjects in IM-EP groups received 0.5mg (N=8) or 2.0mg (N=9) of pWRG/VEE or a saline placebo (N=4) in a 1.0ml injection. Subjects in ID-EP groups received 0.08mg (N=8) or 0.3mg (N=8) of DNA or a saline placebo (N=4) in a 0.15ml injection. Subjects were monitored for a total period of 360 days. No vaccine- or device-related serious adverse events were reported. Based on the results of a subject questionnaire, the IM- and ID-EP procedures were both considered to be generally acceptable for prophylactic vaccine administration, with the acute tolerability of ID EP delivery judged to be greater than that of IM-EP delivery. All subjects (100%) in the high and low dose IM-EP groups developed detectable VEEV-neutralizing antibodies after two or three administrations of pWRG/VEE, respectively. VEEV-neutralizing antibody responses were detected in seven of eight subjects (87.5%) in the high dose and five of eight subjects (62.5%) in the low dose ID-EP groups after three vaccine administrations. There was a correlation between the DNA dose and the magnitude of the resulting VEEV-neutralizing antibody responses for both IM and ID EP delivery. These results indicate that pWRG/VEE delivered by either IM- or ID-EP is safe, tolerable, and immunogenic in humans at the evaluated dose levels. Clinicaltrials.gov registry numberNCT01984983. Venezuelan equine encephalitis virus (VEEV), a mosquito-borne alphavirus, causes periodic epizootics in equines and is a recognized biological defense threat for humans. There are currently no FDA-licensed vaccines against VEEV. We developed a candidate DNA vaccine expressing the E3-E2-6K-E1 genes of VEEV (pWRG/VEE) and performed a Phase 1 clinical study to assess the vaccine's safety, reactogenicity, tolerability, and immunogenicity when administered by intramuscular (IM) or intradermal (ID) electroporation (EP) using the Ichor Medical Systems TriGrid™ Delivery System. Subjects in IM-EP groups received 0.5mg (N=8) or 2.0mg (N=9) of pWRG/VEE or a saline placebo (N=4) in a 1.0ml injection. Subjects in ID-EP groups received 0.08mg (N=8) or 0.3mg (N=8) of DNA or a saline placebo (N=4) in a 0.15ml injection. Subjects were monitored for a total period of 360 days. No vaccine- or device-related serious adverse events were reported. Based on the results of a subject questionnaire, the IM- and ID-EP procedures were both considered to be generally acceptable for prophylactic vaccine administration, with the acute tolerability of ID EP delivery judged to be greater than that of IM-EP delivery. All subjects (100%) in the high and low dose IM-EP groups developed detectable VEEV-neutralizing antibodies after two or three administrations of pWRG/VEE, respectively. VEEV-neutralizing antibody responses were detected in seven of eight subjects (87.5%) in the high dose and five of eight subjects (62.5%) in the low dose ID-EP groups after three vaccine administrations. There was a correlation between the DNA dose and the magnitude of the resulting VEEV-neutralizing antibody responses for both IM and ID EP delivery. These results indicate that pWRG/VEE delivered by either IM- or ID-EP is safe, tolerable, and immunogenic in humans at the evaluated dose levels. Clinicaltrials.gov registry number NCT01984983.Venezuelan equine encephalitis virus (VEEV), a mosquito-borne alphavirus, causes periodic epizootics in equines and is a recognized biological defense threat for humans. There are currently no FDA-licensed vaccines against VEEV. We developed a candidate DNA vaccine expressing the E3-E2-6K-E1 genes of VEEV (pWRG/VEE) and performed a Phase 1 clinical study to assess the vaccine's safety, reactogenicity, tolerability, and immunogenicity when administered by intramuscular (IM) or intradermal (ID) electroporation (EP) using the Ichor Medical Systems TriGrid™ Delivery System. Subjects in IM-EP groups received 0.5mg (N=8) or 2.0mg (N=9) of pWRG/VEE or a saline placebo (N=4) in a 1.0ml injection. Subjects in ID-EP groups received 0.08mg (N=8) or 0.3mg (N=8) of DNA or a saline placebo (N=4) in a 0.15ml injection. Subjects were monitored for a total period of 360 days. No vaccine- or device-related serious adverse events were reported. Based on the results of a subject questionnaire, the IM- and ID-EP procedures were both considered to be generally acceptable for prophylactic vaccine administration, with the acute tolerability of ID EP delivery judged to be greater than that of IM-EP delivery. All subjects (100%) in the high and low dose IM-EP groups developed detectable VEEV-neutralizing antibodies after two or three administrations of pWRG/VEE, respectively. VEEV-neutralizing antibody responses were detected in seven of eight subjects (87.5%) in the high dose and five of eight subjects (62.5%) in the low dose ID-EP groups after three vaccine administrations. There was a correlation between the DNA dose and the magnitude of the resulting VEEV-neutralizing antibody responses for both IM and ID EP delivery. These results indicate that pWRG/VEE delivered by either IM- or ID-EP is safe, tolerable, and immunogenic in humans at the evaluated dose levels. Clinicaltrials.gov registry number NCT01984983. Venezuelan equine encephalitis virus (VEEV), a mosquito-borne alphavirus, causes periodic epizootics in equines and is a recognized biological defense threat for humans. There are currently no FDA-licensed vaccines against VEEV. We developed a candidate DNA vaccine expressing the E3-E2-6K-E1 genes of VEEV (pWRG/VEE) and performed a Phase 1 clinical study to assess the vaccine's safety, reactogenicity, tolerability, and immunogenicity when administered by intramuscular (IM) or intradermal (ID) electroporation (EP) using the Ichor Medical Systems TriGrid™ Delivery System. Subjects in IM-EP groups received 0.5mg (N=8) or 2.0mg (N=9) of pWRG/VEE or a saline placebo (N=4) in a 1.0ml injection. Subjects in ID-EP groups received 0.08mg (N=8) or 0.3mg (N=8) of DNA or a saline placebo (N=4) in a 0.15ml injection. Subjects were monitored for a total period of 360 days. No vaccine- or device-related serious adverse events were reported. Based on the results of a subject questionnaire, the IM- and ID-EP procedures were both considered to be generally acceptable for prophylactic vaccine administration, with the acute tolerability of ID EP delivery judged to be greater than that of IM-EP delivery. All subjects (100%) in the high and low dose IM-EP groups developed detectable VEEV-neutralizing antibodies after two or three administrations of pWRG/VEE, respectively. VEEV-neutralizing antibody responses were detected in seven of eight subjects (87.5%) in the high dose and five of eight subjects (62.5%) in the low dose ID-EP groups after three vaccine administrations. There was a correlation between the DNA dose and the magnitude of the resulting VEEV-neutralizing antibody responses for both IM and ID EP delivery. These results indicate that pWRG/VEE delivered by either IM- or ID-EP is safe, tolerable, and immunogenic in humans at the evaluated dose levels. Clinicaltrials.gov registry number NCT01984983. Venezuelan equine encephalitis virus (VEEV), a mosquito-borne alphavirus, causes periodic epizootics in equines and is a recognized biological defense threat for humans. There are currently no FDA-licensed vaccines against VEEV. We developed a candidate DNA vaccine expressing the E3-E2-6K-E1 genes of VEEV (pWRG/VEE) and performed a Phase 1 clinical study to assess the vaccine's safety, reactogenicity, tolerability, and immunogenicity when administered by intramuscular (IM) or intradermal (ID) electroporation (EP) using the Ichor Medical Systems TriGrid(TM) Delivery System. Subjects in IM-EP groups received 0.5mg (N=8) or 2.0mg (N=9) of pWRG/VEE or a saline placebo (N=4) in a 1.0ml injection. Subjects in ID-EP groups received 0.08mg (N=8) or 0.3mg (N=8) of DNA or a saline placebo (N=4) in a 0.15ml injection. Subjects were monitored for a total period of 360 days. No vaccine- or device-related serious adverse events were reported. Based on the results of a subject questionnaire, the IM- and ID-EP procedures were both considered to be generally acceptable for prophylactic vaccine administration, with the acute tolerability of ID EP delivery judged to be greater than that of IM-EP delivery. All subjects (100%) in the high and low dose IM-EP groups developed detectable VEEV-neutralizing antibodies after two or three administrations of pWRG/VEE, respectively. VEEV-neutralizing antibody responses were detected in seven of eight subjects (87.5%) in the high dose and five of eight subjects (62.5%) in the low dose ID-EP groups after three vaccine administrations. There was a correlation between the DNA dose and the magnitude of the resulting VEEV-neutralizing antibody responses for both IM and ID EP delivery. These results indicate that pWRG/VEE delivered by either IM- or ID-EP is safe, tolerable, and immunogenic in humans at the evaluated dose levels. Clinicaltrials.gov registry number NCT01984983. |
| Author | Hannaman, Drew Schmaljohn, Connie S. Ellefsen, Barry Dupuy, Lesley C. |
| Author_xml | – sequence: 1 givenname: Drew surname: Hannaman fullname: Hannaman, Drew organization: Ichor Medical Systems, Inc., San Diego, CA, USA – sequence: 2 givenname: Lesley C. surname: Dupuy fullname: Dupuy, Lesley C. organization: United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD, USA – sequence: 3 givenname: Barry surname: Ellefsen fullname: Ellefsen, Barry organization: Ichor Medical Systems, Inc., San Diego, CA, USA – sequence: 4 givenname: Connie S. surname: Schmaljohn fullname: Schmaljohn, Connie S. email: connie.s.schmaljohn.civ@mail.mil organization: United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD, USA |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/27206386$$D View this record in MEDLINE/PubMed |
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| Keywords | DNA vaccine Human Intradermal Venezuelan equine encephalitis Electroporation Clinical trial Intramuscular Phase 1 |
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| References | Badger, Richardson, Dasilva, Richards, Josleyn, Dupuy (bib0115) 2011; 29 Schmaljohn, Vanderzanden, Bray, Custer, Meyer, Li (bib0130) 1997; 71 Hooper, Moon, Paolino, Newcomer, McLain, Josleyn (bib0120) 2014; 20 Hodgson, Ludwig, Smith (bib0125) 1999; 17 McKinney, Berge, Sawyer, Tigertt, Crozier (bib0095) 1963; 12 Griffin (bib0070) 2001 Tsai (bib0080) 1991; 5 Pittman, Makuch, Mangiafico, Cannon, Gibbs, Peters (bib0100) 1996; 14 Cole, May, Robinson (bib0090) 1973; 25 Bale (bib0075) 1993; 77 Dupuy, Richards, Ellefsen, Chau, Luxembourg, Hannaman (bib0110) 2011; 18 Steele, Reed, Glass, Hart, Ludwig, Pratt (bib0085) 2007 Dupuy, Schmaljohn (bib0105) 2009; 8 Steele (10.1016/j.vaccine.2016.04.077_bib0085) 2007 Pittman (10.1016/j.vaccine.2016.04.077_bib0100) 1996; 14 Bale (10.1016/j.vaccine.2016.04.077_bib0075) 1993; 77 Cole (10.1016/j.vaccine.2016.04.077_bib0090) 1973; 25 McKinney (10.1016/j.vaccine.2016.04.077_bib0095) 1963; 12 Hodgson (10.1016/j.vaccine.2016.04.077_bib0125) 1999; 17 Tsai (10.1016/j.vaccine.2016.04.077_bib0080) 1991; 5 Schmaljohn (10.1016/j.vaccine.2016.04.077_bib0130) 1997; 71 Badger (10.1016/j.vaccine.2016.04.077_bib0115) 2011; 29 Dupuy (10.1016/j.vaccine.2016.04.077_bib0110) 2011; 18 Griffin (10.1016/j.vaccine.2016.04.077_bib0070) 2001 Dupuy (10.1016/j.vaccine.2016.04.077_bib0105) 2009; 8 Hooper (10.1016/j.vaccine.2016.04.077_bib0120) 2014; 20 |
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man publication-title: Am J Trop Med Hyg – start-page: 917 year: 2001 end-page: 962 ident: bib0070 article-title: Alphaviruses publication-title: Fields virology – volume: 77 start-page: 25 year: 1993 end-page: 42 ident: bib0075 article-title: Viral encephalitis publication-title: Med Clin North Am – volume: 14 start-page: 337 year: 1996 end-page: 343 ident: bib0100 article-title: Long-term duration of detectable neutralizing antibodies after administration of live-attenuated VEE vaccine and following booster vaccination with inactivated VEE vaccine publication-title: Vaccine – volume: 5 start-page: 73 year: 1991 end-page: 102 ident: bib0080 article-title: Arboviral infections in the United States publication-title: Infect Dis Clin North Am – volume: 18 start-page: 707 year: 2011 end-page: 716 ident: bib0110 article-title: 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 publication-title: Clin Vaccine Immunol – volume: 25 start-page: 262 year: 1973 end-page: 265 ident: bib0090 article-title: Formalin-inactivated Venezuelan equine encephalomyelitis (Trinidad strain) vaccine produced in rolling-bottle cultures of chicken embryo cells publication-title: Appl Microbiol – volume: 17 start-page: 1151 year: 1999 end-page: 1160 ident: bib0125 article-title: Expression, processing, and immunogenicity of the structural proteins of Venezuelan equine encephalitis virus from recombinant baculovirus vectors publication-title: Vaccine – volume: 20 start-page: 110 year: 2014 end-page: 117 ident: bib0120 article-title: A Phase 1 clinical trial of Hantaan virus and Puumala virus M-segment DNA vaccines for haemorrhagic fever with renal syndrome delivered by intramuscular electroporation publication-title: Clin Microbiol Infect – volume: 14 start-page: 337 year: 1996 ident: 10.1016/j.vaccine.2016.04.077_bib0100 article-title: Long-term duration of detectable neutralizing antibodies after administration of live-attenuated VEE vaccine and following booster vaccination with inactivated VEE vaccine publication-title: Vaccine doi: 10.1016/0264-410X(95)00168-Z – volume: 18 start-page: 707 year: 2011 ident: 10.1016/j.vaccine.2016.04.077_bib0110 article-title: 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 publication-title: Clin Vaccine Immunol doi: 10.1128/CVI.00030-11 – volume: 5 start-page: 73 year: 1991 ident: 10.1016/j.vaccine.2016.04.077_bib0080 article-title: Arboviral infections in the United States publication-title: Infect Dis Clin North Am doi: 10.1016/S0891-5520(20)30389-5 – volume: 77 start-page: 25 year: 1993 ident: 10.1016/j.vaccine.2016.04.077_bib0075 article-title: Viral encephalitis publication-title: Med Clin North Am doi: 10.1016/S0025-7125(16)30270-X – start-page: 917 year: 2001 ident: 10.1016/j.vaccine.2016.04.077_bib0070 article-title: Alphaviruses – volume: 25 start-page: 262 year: 1973 ident: 10.1016/j.vaccine.2016.04.077_bib0090 article-title: Formalin-inactivated Venezuelan equine encephalomyelitis (Trinidad strain) vaccine produced in rolling-bottle cultures of chicken embryo cells publication-title: Appl Microbiol doi: 10.1128/AEM.25.2.262-265.1973 – volume: 29 start-page: 6728 year: 2011 ident: 10.1016/j.vaccine.2016.04.077_bib0115 article-title: Development and application of a flow cytometric potency assay for DNA vaccines publication-title: Vaccine doi: 10.1016/j.vaccine.2010.12.053 – volume: 8 start-page: 1739 year: 2009 ident: 10.1016/j.vaccine.2016.04.077_bib0105 article-title: DNA vaccines for biodefense publication-title: Expert Rev Vaccines doi: 10.1586/erv.09.132 – volume: 12 start-page: 597 year: 1963 ident: 10.1016/j.vaccine.2016.04.077_bib0095 article-title: Use of an attenuated strain of Venezuelan equine encephalomyelitis virus for immunization in man publication-title: Am J Trop Med Hyg doi: 10.4269/ajtmh.1963.12.597 – volume: 71 start-page: 9563 year: 1997 ident: 10.1016/j.vaccine.2016.04.077_bib0130 article-title: Naked DNA vaccines expressing the prM and E genes of Russian spring summer encephalitis virus and Central European encephalitis virus protect mice from homologous and heterologous challenge publication-title: J Virol doi: 10.1128/JVI.71.12.9563-9569.1997 – start-page: 241 year: 2007 ident: 10.1016/j.vaccine.2016.04.077_bib0085 article-title: Alphavirus encephalitides – volume: 17 start-page: 1151 year: 1999 ident: 10.1016/j.vaccine.2016.04.077_bib0125 article-title: Expression, processing, and immunogenicity of the structural proteins of Venezuelan equine encephalitis virus from recombinant baculovirus vectors publication-title: Vaccine doi: 10.1016/S0264-410X(98)00335-1 – volume: 20 start-page: 110 issue: Suppl. 5 year: 2014 ident: 10.1016/j.vaccine.2016.04.077_bib0120 article-title: A Phase 1 clinical trial of Hantaan virus and Puumala virus M-segment DNA vaccines for haemorrhagic fever with renal syndrome delivered by intramuscular electroporation publication-title: Clin Microbiol Infect doi: 10.1111/1469-0691.12553 |
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| SubjectTerms | Adolescent Adult Allergy and Immunology Alphavirus antibodies Antibodies, Neutralizing - blood Antibodies, Viral - blood Clinical trial clinical trials Deoxyribonucleic acid DNA DNA vaccine Double-Blind Method Electroporation Encephalitis Encephalitis Virus, Venezuelan Equine Encephalomyelitis, Venezuelan Equine - prevention & control Female genes Hispanic Americans horses Human Humans immune response Immunogenicity Immunogenicity, Vaccine Immunoglobulins Injection Injections, Intradermal Injections, Intramuscular Intradermal Intramuscular Male Middle Aged Phase 1 questionnaires R&D recombinant vaccines Reoviridae Research & development Studies Togaviridae Vaccines Vaccines, DNA - administration & dosage Vaccines, DNA - therapeutic use Venezuelan equine encephalitis Venezuelan equine encephalitis virus Viral Vaccines - administration & dosage Viral Vaccines - therapeutic use Young Adult |
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