+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Lactogenic immunity in transgenic mice producing recombinant antibodies neutralizing coronavirus



Lactogenic immunity in transgenic mice producing recombinant antibodies neutralizing coronavirus



Advances in Experimental Medicine and Biology 440: 675-686



Protection against coronavirus infections can be provided by the oral administration of virus neutralizing antibodies. To provide lactogenic immunity, eighteen lines of transgenic mice secreting a recombinant IgG1 monoclonal antibody (rIgG1) and ten lines of transgenic mice secreting recombinant IgA monoclonal antibodies (rIgA) neutralizing transmissible gastroenteritis coronavirus (TGEV) into the milk were generated. Genes encoding the light and heavy chains of monoclonal antibody (MAb) 6A.C3 were expressed under the control of regulatory sequences derived from the mouse genomic DNA encoding the whey acidic protein (WAP) and beta-lactoglobulin (BLG), which are highly abundant milk proteins. The MAb 6A.C3 binds to a highly conserved epitope present in coronaviruses of several species. This MAb does not allow the selection of neutralization escaping virus mutants. The antibody was expressed in the milk of transgenic mice with titers of one million as determined by RIA, and neutralized TGEV infectivity by one million fold corresponding to immunoglobulin concentrations of 5 to 6 mg per ml. Matrix attachment regions (MAR) sequences were not essential for rIgG1 transgene expression, but co-microinjection of MAR and antibody genes led to a twenty to ten thousand-fold increase in the antibody titer in 50% of the rIgG1 transgenic animals generated. Co-microinjection of the genomic BLG gene with rIgA light and heavy chain genes led to the generation of transgenic mice carrying the three transgenes. The highest antibody titers were produced by transgenic mice that had integrated the antibody and BLG genes, although the number of transgenic animals generated does not allow a definitive conclusion on the enhancing effect of BLG co-integration. Antibody expression levels were transgene copy number independent and integration site dependent. The generation of transgenic animals producing virus neutralizing antibodies in the milk could be a general approach to provide protection against neonatal infections of the enteric tract.

Please choose payment method:






(PDF emailed within 1 workday: $29.90)

Accession: 046515398

Download citation: RISBibTeXText

PMID: 9782344


Related references

Transgenic mice secreting coronavirus neutralizing antibodies into the milk. Journal of Virology 72(5): 3762-3772, 1998

Neutralizing antibody and protective immunity to SARS coronavirus infection of mice induced by a soluble recombinant polypeptide containing an N-terminal segment of the spike glycoprotein. Virology 334(2): 160-165, 2005

Engineering passive immunity in transgenic mice secreting virus-neutralizing antibodies in milk. Nature Biotechnology 16(4): 349-354, 1998

Purified coronavirus spike protein nanoparticles induce coronavirus neutralizing antibodies in mice. Vaccine 32(26): 3169-3174, 2014

A recombinant baculovirus-expressed S glycoprotein vaccine elicits high titers of SARS-associated coronavirus (SARS-CoV) neutralizing antibodies in mice. Vaccine 24(17): 3624-3631, 2006

Recombinant Mycobacterium bovis BCG producing the N-terminal half of SIV mac251 Env antigen induces neutralizing antibodies and CTL responses in mice and guinea pigs. Research in Immunology 149(1): 101, 1998

Recombinant Mycobacterium bovis BCG producing the N-terminal half of SIVmac251 Env antigen induces neutralizing antibodies and cytotoxic T lymphocyte responses in mice and guinea pigs. Aids Research and Human Retroviruses 13(18): 1573-1581, 1997

Characterization of phage-displayed recombinant anti-idiotypic antibody fragments against coronavirus-neutralizing monoclonal antibodies. Viral Immunology 10(4): 175-182, 1997

Prime-boost immunization with DNA, recombinant fowlpox virus and VLP(SHIV) elicit both neutralizing antibodies and IFNgamma-producing T cells against the HIV-envelope protein in mice that control env-bearing tumour cells. Vaccine 25(11): 2128-2138, 2007

Transgenic mice and transhybridomas producing chimeric mouse/human anti-human interleukin-2 receptor recombinant antibodies. Gene (Amsterdam) 137(1): 101-107, 1993

Neutralizing (54K) and non-neutralizing (54K and 48K) monoclonal antibodies against structural and non-structural yellow fever virus proteins confer immunity in mice. Journal of General Virology 67: 591-595, 1986

Lactogenic immunity following vaccination of cattle with bovine coronavirus. Vaccine 19(2-3): 189-196, 15 September, 2000

Lactogenic immunity of cattle vaccinated against bovine coronavirus. Medicina Veterinaria 17(11): 264-272, 2000

Htlv iii neutralizing antibodies and cellular immunity elicited by recombinant envelope proteins. Journal of Cellular Biochemistry Suppl. (11 Part D): 34, 1987

The immunity induced by recombinant spike proteins of SARS coronavirus in Balb/c mice. Journal of Huazhong University of Science and Technology. Medical Sciences 27(3): 221-224, 2007