Dataset Information

Antiviral Biologic Produced in DNA Vaccine/Goose Platform Protects Hamsters Against Hantavirus Pulmonary Syndrome When Administered Post-exposure.

ABSTRACT: Andes virus (ANDV) and ANDV-like viruses are responsible for most hantavirus pulmonary syndrome (HPS) cases in South America. Recent studies in Chile indicate that passive transfer of convalescent human plasma shows promise as a possible treatment for HPS. Unfortunately, availability of convalescent plasma from survivors of this lethal disease is very limited. We are interested in exploring the concept of using DNA vaccine technology to produce antiviral biologics, including polyclonal neutralizing antibodies for use in humans. Geese produce IgY and an alternatively spliced form, IgY?Fc, that can be purified at high concentrations from egg yolks. IgY lacks the properties of mammalian Fc that make antibodies produced in horses, sheep, and rabbits reactogenic in humans. Geese were vaccinated with an ANDV DNA vaccine encoding the virus envelope glycoproteins. All geese developed high-titer neutralizing antibodies after the second vaccination, and maintained high-levels of neutralizing antibodies as measured by a pseudovirion neutralization assay (PsVNA) for over 1 year. A booster vaccination resulted in extraordinarily high levels of neutralizing antibodies (i.e., PsVNA80 titers >100,000). Analysis of IgY and IgY?Fc by epitope mapping show these antibodies to be highly reactive to specific amino acid sequences of ANDV envelope glycoproteins. We examined the protective efficacy of the goose-derived antibody in the hamster model of lethal HPS. ?-ANDV immune sera, or IgY/IgY?Fc purified from eggs, were passively transferred to hamsters subcutaneously starting 5 days after an IM challenge with ANDV (25 LD50). Both immune sera, and egg-derived purified IgY/IgY?Fc, protected 8 of 8 and 7 of 8 hamsters, respectively. In contrast, all hamsters receiving IgY/IgY?Fc purified from normal geese (n=8), or no-treatment (n=8), developed lethal HPS. These findings demonstrate that the DNA vaccine/goose platform can be used to produce a candidate antiviral biological product capable of preventing a lethal disease when administered post-exposure.

SUBMITTER: Haese N

PROVIDER: S-EPMC4457835 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Antiviral Biologic Produced in DNA Vaccine/Goose Platform Protects Hamsters Against Hantavirus Pulmonary Syndrome When Administered Post-exposure.

Haese Nicole N Brocato Rebecca L RL Henderson Thomas T Nilles Matthew L ML Kwilas Steve A SA Josleyn Matthew D MD Hammerbeck Christopher D CD Schiltz James J Royals Michael M Ballantyne John J Hooper Jay W JW Bradley David S DS

PLoS neglected tropical diseases 20150605 6

Andes virus (ANDV) and ANDV-like viruses are responsible for most hantavirus pulmonary syndrome (HPS) cases in South America. Recent studies in Chile indicate that passive transfer of convalescent human plasma shows promise as a possible treatment for HPS. Unfortunately, availability of convalescent plasma from survivors of this lethal disease is very limited. We are interested in exploring the concept of using DNA vaccine technology to produce antiviral biologics, including polyclonal neutraliz ...[more]

PMID: 26046641

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Project description:ImportanceInfusion reactions occur in 7% to 20% of patients receiving biologics. Home infusions are convenient and incur lower costs but may be associated with more adverse events; the safety of receiving biologic infusions for immune-mediated diseases at home remains unclear.ObjectiveTo assess whether patients receiving home biologic infusions have increased adverse events requiring emergency department (ED) or hospital admission compared with patients receiving facility infusions.Design, setting, and participantsThis retrospective cohort study used administrative claims data from a large national insurer for adult patients who received biologic infusions for immune-mediated disease between January 2007 and December 2017. Patients with hematologic malignant neoplasms or bone marrow transplantation were excluded. Data were analyzed from August 2019 to October 2020.Main outcomes and measuresED or hospital admission on the same or next day after administration of a biologic infusion at home vs at a facility; secondary outcomes included discontinuation of the biologic after an ED or hospital admission and postinfusion mortality.ResultsOf a total of 57 220 patients (mean [SD] age, 50.1 [14.8] years; 512 314 [68.1%] women) who received 752 150 biologic infusions (34 078 home infusions [4.5%] to 3954 patients and 718 072 facility infusions [95.5%] to 54 770 patients), patients who received home infusions were younger (mean [SD] age, 43.2 [13.2] vs 51.3 [14.8] years), more likely to be men (14 031 [41.2%] vs 225 668 [31.4%]), and had a lower Charlson comorbidity score compared with patients who received facility infusions (mean [SD] score, 0.5 [1.0] vs 1.1 [1.3]). Home infusions were associated with 25% increased odds of ED or hospital admission on the same or next day after the infusion (odds ratio [OR], 1.25; 95% CI, 1.09-1.44; P = .002) and 28% increased odds of discontinuation of the biologic after the ED or hospital admission (OR, 1.28; 95% CI, 1.08-1.51; P = .005). There was no difference in postinfusion mortality between home or facility infusions. The rates of adverse events were highest with home infusions of tocilizumab (48 of 481 infusions [10.0%]), vedolizumab (150 of 2681 infusions [5.6%]), and infliximab (1085 of 20 653 infusions [5.3%]), although the number of tocilizumab and vedolizumab infusions was low.Conclusions and relevanceIn this study, biologic infusions administered at home, compared with those administered at a facility, were associated with increased adverse events requiring escalation of care. Because the number of home infusions has increased and is expected to continue to rise, the safety implications of administering biologic infusions at home needs to be further assessed.

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Dataset Information

Antiviral Biologic Produced in DNA Vaccine/Goose Platform Protects Hamsters Against Hantavirus Pulmonary Syndrome When Administered Post-exposure.

Publications

Antiviral Biologic Produced in DNA Vaccine/Goose Platform Protects Hamsters Against Hantavirus Pulmonary Syndrome When Administered Post-exposure.

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