Journal article
Virus-neutralizing monoclonal antibody expressed in milk of transgenic mice provides full protection against virus-induced encephalitis
Journal of virology, Vol.75(6), pp.2803-2809
03/2001
DOI: 10.1128/JVI.75.6.2803-2809.2001
PMCID: PMC115905
PMID: 11222704
Abstract
Neutralizing antibodies represent a major host defense mechanism against viral infections. In mammals, passive immunity is provided by neutralizing antibodies passed to the offspring via the placenta or the milk as immunoglobulin G and secreted immunoglobulin A. With the long-term goal of producing virus-resistant livestock, we have generated mice carrying transgenes that encode the light and heavy chains of an antibody that is able to neutralize the neurotropic JHM strain of murine hepatitis virus (MHV-JHM). MHV-JHM causes acute encephalitis and acute and chronic demyelination in susceptible strains of mice and rats. Transgene expression was targeted to the lactating mammary gland by using the ovine beta-lactoglobulin promoter. Milk from these transgenic mice contained up to 0.7 mg of recombinant antibody/ml. In vitro analysis of milk derived from different transgenic lines revealed a linear correlation between antibody expression and virus-neutralizing activity, indicating that the recombinant antibody is the major determinant of MHV-JHM neutralization in murine milk. Offspring of transgenic and control mice were challenged with a lethal dose of MHV-JHM. Litters suckling nontransgenic dams succumbed to fatal encephalitis, whereas litters suckling transgenic dams were fully protected against challenge, irrespective of whether they were transgenic. This demonstrates that a single neutralizing antibody expressed in the milk of transgenic mice is sufficient to completely protect suckling offspring against MHV-JHM-induced encephalitis.
Details
- Title: Subtitle
- Virus-neutralizing monoclonal antibody expressed in milk of transgenic mice provides full protection against virus-induced encephalitis
- Creators
- A F Kolb - Cell Physiology Group, Hannah Research Institute, Ayr, United Kingdom. kolba@hri.sari.ac.ukLecia PeweJohn WebsterStanley PerlmanC B WhitelawS G Siddell
- Resource Type
- Journal article
- Publication Details
- Journal of virology, Vol.75(6), pp.2803-2809
- DOI
- 10.1128/JVI.75.6.2803-2809.2001
- PMID
- 11222704
- PMCID
- PMC115905
- NLM abbreviation
- J Virol
- ISSN
- 0022-538X
- eISSN
- 1098-5514
- Publisher
- United States
- Grant note
- R01 NS040438 / NINDS NIH HHS NS 40438 / NINDS NIH HHS
- Language
- English
- Date published
- 03/2001
- Academic Unit
- Microbiology and Immunology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Infectious Disease (Pediatrics)
- Record Identifier
- 9983777348702771
Metrics
16 Record Views