Comparative performance of a licensed anthrax vaccine versus electroporation based delivery of a PA encoding DNA vaccine in rhesus macaques

Livingston, Brian; Little, Stephen F.; Luxembourg, Alain; Ellefsen, Barry; Hannaman, Drew

doi:10.1016/j.vaccine.2009.10.111

Cited by 53 publications

(33 citation statements)

References 50 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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“…Data from these models have demonstrated consistently that as few as two doses of AVA and rPA vaccines separated by 7 to 14 days can provide significant short-term protection against acute inhalation anthrax (9, 36, 55). Livingston and coworkers (27) demonstrated that 2 doses of AVA given 8 weeks apart provided 100% protection (n ϭ 5) in rhesus macaques up to 1 year after the first vaccination. In contrast, Little and coworkers (22) reported for rabbits that a 2-dose rPA-Alhydrogel formulation (0 and 4 weeks) afforded 74.1% (20/27 animals) and 37.5% (9/24 animals) protection 6 months and 12 months after the first vaccination, respectively.…”

Section: Discussionmentioning

confidence: 99%

A Three-Dose Intramuscular Injection Schedule of Anthrax Vaccine Adsorbed Generates Sustained Humoral and Cellular Immune Responses to Protective Antigen and Provides Long-Term Protection against Inhalation Anthrax in Rhesus Macaques

Quinn¹,

Sabourin²,

Niemuth³

et al. 2012

Clin. Vaccine Immunol.

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05). PA-specific gamma interferon (IFN-␥) and interleukin-4 (IL-4) CD4؉ cell frequencies and T cell stimulation indices were sustained through 50.5 months (the last time point measured). PA-specific memory B cell frequencies were highly variable but, in general, were detectable in peripheral blood mononuclear cells (PBMC) by 2 months, were significantly above control levels by 7 months, and remained detectable in the HuAVA and 1:5 and 1:20 AVA groups through 42 months (the last time point measured). HuAVA and diluted AVA elicited a combined Th1/Th2 response and robust immunological priming, with sustained production of high-avidity PA-specific functional antibody, long-term immune cell competence, and immunological memory (30 months for 1:20 AVA and 52 months for 1:10 AVA). Vaccinated animals surviving inhalation anthrax developed high-magnitude anamnestic anti-PA IgG and TNA responses.

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“…For the immunization via i.m. electroporation (EP) the animals were, as previously described, vaccinated with a "needle-style" EP device (TriGrid delivery system; Ichor Medical Systems, San Diego, CA) (30)(31)(32). For the i.d.…”

Section: Methodsmentioning

confidence: 99%

Novel Vaccine Regimen Elicits Strong Airway Immune Responses and Control of Respiratory Syncytial Virus in Nonhuman Primates

Grünwald

Tenbusch

Schulte

et al. 2014

J Virol

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Induction of long-lasting immunity against viral respiratory tract infections؉ and CD8 ؉ T cell response in the lower respiratory tract and protection from intranasal hRSV challenge. Thus, parenteral DNA priming followed by booster immunization targeted to a mucosal inductive site constitutes an effective vaccine regimen for eliciting protective immune responses at mucosal effector sites. IMPORTANCEThe human respiratory syncytial virus (hRSV) is the most common cause of severe respiratory tract disease in infancy and leads to substantial morbidity and morality in the elderly. In this study, we compared the immunogenicity and efficacy of several genebased immunization protocols in rhesus macaques. Thereby, we found that the combination of an initially parenterally delivered DNA vaccine with a subsequent atraumatic tonsillar adenoviral vector immunization results in a strong systemic immune response accompanied by an exceptional high T-cell response in the mucosa. Strikingly, these animals were protected against a RSV challenge infection controlling the viral replication indicated by a 1,000-fold-lower viral load in the lower respiratory tract. Since mucosal cellular responses of this strength had not been described in earlier RSV vaccine studies, this heterologous DNA prime-tonsillar boost vaccine strategy is very promising and should be pursued for further preclinical and clinical testing.

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Comparative performance of a licensed anthrax vaccine versus electroporation based delivery of a PA encoding DNA vaccine in rhesus macaques

Cited by 53 publications

References 50 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 Three-Dose Intramuscular Injection Schedule of Anthrax Vaccine Adsorbed Generates Sustained Humoral and Cellular Immune Responses to Protective Antigen and Provides Long-Term Protection against Inhalation Anthrax in Rhesus Macaques

Novel Vaccine Regimen Elicits Strong Airway Immune Responses and Control of Respiratory Syncytial Virus in Nonhuman Primates

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