Mouse × pig chimeric antibodies expressed in Baculovirus retain the same properties of their parent antibodies

Abstract

The development of hybridoma and recombinant DNA technologies has made it possible to use antibodies against cancer, autoimmune disorders, and infectious diseases in humans. These advances in therapy, as well as immunoprophylaxis, could also make it possible to use these technologies in agricultural species of economic importance such as pigs. Porcine reproductive and respiratory syndrome virus (PRRSV) is an arterivirus causing very important economic losses to the industry. Passive transfer of antibodies obtained by biotechnology could be used in the future to complement or replace vaccination against this and other pig pathogens. To this end, we constructed and studied the properties of chimeric mouse x pig anti-PRRSV antibodies. We cloned the constant regions of gamma-1 and gamma-2 heavy chains and the lambda light chain of pig antibodies in frame with the variable regions of heavy and light chains of mouse monoclonal antibody ISU25C1, which has neutralizing activity against PRRSV. The coding regions for chimeric IgG1 and IgG2 were expressed in a baculovirus expression system. Both chimeric antibodies recognized PRRSV in ELISA as well as in a Western-blot format and, more importantly, were able to neutralize PRRSV in the same fashion as the parent mouse monoclonal antibody ISU25C1. In addition, we show that both pig IgG1 and IgG2 antibodies could bind complement component C1q, with IgG2 being more efficient than IgG1 in binding C1q. Expressing chimeric pig antibodies with protective capabilities offers a new alternative strategy for infectious disease control in domestic pigs.

Development of a neutralizing mouse-pig chimeric antibody with therapeutic potential againstHaemophilus parasuisinPichia pastoris

“…Heterologous expression of mouse–pig chimeric antibody has been reported in Escherichia coli as well as in baculovirus (Jar et al ., ; Pyo et al ., ). Escherichia coli expression system is simple and low costs; however, the expressed proteins may lack important post‐translational modifications.…”

“…To our knowledge, there was no data to show the therapeutic effect of mouse–pig chimeric antibody in animals, although the mouse–pig chimeric antibody have been reported (Jar et al ., ; Pyo et al ., ). In this study, our findings showed that mouse–pig chimeric antibody partially protected mice against lethal challenge with H. parasuis HLJ‐018, suggesting that variable region of chimeric antibody has biologic activity in vivo (Fig.…”

“…The production of chimeric antibodies using recombinant DNA technologies for therapy and prophylaxis in human has been used widely in the last years (Johnson et al ., ; Zeitlin et al ., ; Oliphant et al ., ; Hu et al ., ). Furthermore, recombinant antibodies have been developed for the control of infectious diseases in animals (Jar et al ., ; Pyo et al ., ).…”

Recombinant Antibodies in Veterinary Medicine: An Update

“…The authors demonstrated that viral replication was inhibited in a stable Marc-145 cell line expressing Nb6, proving the potential of sdAb (Nb6) as a new form of protection against PRRSV ( 32 ). Similarly, a chimeric mouse x pig antibody anti-linear GP5 epitope had neutralizing activity similar to that of the native mAb (ISU25C1) ( 33 ).…”

Lepidopteran cells, an alternative for the production of recombinant antibodies?

“…Several immunoglobulin isotypes from many different species, including murine IgG, 2,3,[21][22][23][24][25] chimeric IgG, [26][27][28][29][30] human IgG, [31][32][33][34][35][36][37][38][39] IgA, [40][41][42] IgM 41 and IgE, [43][44][45] as well as pig Igs 30,45 have been successfully expressed in insect cells. These molecules are all correctly processed (signal peptide cleaved), glycosylated and assembled (H2L2) with a production rate varying from 0.75 to 100 mg/l, depending on the antibody ( …”