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Cited by 54Virus-based gene therapy researchRespiratory viral infections researchRNA Interference and Gene Delivery

Genetic delivery of an anti-RSV antibody to protect against pulmonary infection with RSV

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Skaricic, Davor, Traube, Chani, De, Bishnu, Joh, Ju, Boyer, Julie, Crystal, Ronald G., Worgall, Stefan·2008·Virology
DOI 10.1016/j.virol.2008.04.016
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Abstract

Respiratory syncytial virus (RSV) is a common cause of severe lower respiratory tract infections. Protection against infection with RSV can be achieved by monthly administration of the humanized monoclonal antibody palivizumab. The present study analyzes if genetic delivery of a murine version of palivizumab by single administration would achieve high-level and sustained antibody expression to protect mice against pulmonary infection with RSV. A murine version of the palivizumab antibody was constructed by replacing the human sequences with sequences from the constant region of a murine IgG1 antibody, while preserving the complementarity-determining region. As a proof-of-principle to test the validity of the strategy, the coding sequence for the heavy and light chains were cloned into a replication-defective serotype 5 human adenovirus vector (AdalphaRSV). Antibody expression and specificity for RSV was confirmed by Western analysis. To determine if AdalphaRSV would mediate production of anti-RSV antibodies in vivo, 5x10(10) particle units of AdalphaRSV or a control vector without transgene (AdNull), were administered intravenously to BALB/c mice. RSV neutralizing antibodies were detected in the serum after 4 days in mice receiving AdalphaRSV but not in AdNull-infected or naive mice (p<0.05). The mice that had received AdalphaRSV had at least 5.4-fold lower RSV titers in the lung 4 days following intranasal challenge with RSV compared to the AdNull or naive group (p<0.01). To evaluate long-term protection, the antibody construct was expressed in a non-human primate serotype rh.10 adeno-associated virus vector (AAVrh.10alphaRSV). RSV neutralizing antibodies were detected in serum and bronchoalveolar lavage fluid for up to 21 wk following intrapleural administration of AAVrh.10alphaRSV, but not with a control AAV vector expressing an unrelated transgene (AAVrh.10alpha1AT). Following challenge with RSV at 7 or 21 wk, 14.3-fold and 10.6-fold lower RSV titers were observed after 4 days in the lungs of mice that had received AAVrh.10alphaRSV compared to AAVrh.10alpha1AT (p<0.05). Together these data demonstrate that a gene transfer strategy for delivery of an anti-RSV antibody can generate protective immunity in mice against RSV infection in the respiratory tract and may provide an alternative to the administration of the antibody itself.

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  • Using viral vectors, sustained expression of low to mid microgram per milliliter levels was obtained in different models and conferred protection against influenza and RSV challenges.

    “Using viral vectors, sustained expression of low to mid microgram per milliliter levels was obtained in different models and conferred protection against influenza and RSV challenges (Lewis et al, 2002; Skaricic et al, 2008; Balazs et al, 2011).”

    From mRNA mediates passive vaccination against infectious agents, toxins, and tumors (2017) · cites this paper as Skaricic et al, 2008

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Authors
Skaricic, D., Traube, C., De, B., Joh, J., Boyer, J., Crystal, R. G., & Worgall, S.
Affiliations
Cornell University (US)
ORCID
Venue
Virology
Publisher
Elsevier BV
Published
2008-08
Volume
378
Issue
1
Pages
79-85
ISSN
0042-6822 (ISSN-L)
DOI
10.1016/j.virol.2008.04.016
OpenAlex
W1969913120
Cited by
54
References
38
Citations by year
2025: 2 · 2024: 1 · 2023: 2 · 2022: 3 · 2021: 7 · 2020: 3 · 2019: 3 · 2018: 3 · 2017: 5 · 2016: 3 · 2015: 5 · 2014: 6 · 2013: 3
FWCI
1.52
Type
journal article
Language
en
Open access
Licence
Locations
  • Virology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
  • Health Sciences › Medicine › Epidemiology › Respiratory viral infections research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
Keywords
respiratory syncytial virus, palivizumab, gene therapy, adenoviral vector, adeno-associated virus vectors, neutralizing antibodies, pulmonary infection, long-term protection, murine monoclonal antibodies, lower respiratory tract infection, non-human primates, mice, bronchoalveolar lavage fluid, intranasal challenge
MeSH terms
Palivizumab, Dependovirus, Adenoviridae, Animals, Antibodies, Monoclonal, Antibodies, Viral, Genetic Vectors, Humans, Neutralization Tests, Respiratory Tract Infections, Genetic Therapy, Treatment Outcome, Respiratory Syncytial Virus, Human, Respiratory Syncytial Virus Infections, Mice, Antibodies, Monoclonal, Humanized

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