A highly expressing, soluble, and stable plant-made IgG fusion vaccine strategy enhances antigen immunogenicity in mice without adjuvant

Abstract

SummaryWhile therapeutics based on fusing a protein of interest to the IgG Fc domain have been enormously successful, fewer studies have investigated the vaccine potential of IgG fusions. In this study, we systematically compared the key properties of a panel of plant-made IgG fusion vaccine candidates targeting Zika virus envelope domain III (ZE3). Complement protein C1q binding of the IgG fusions was enhanced by: 1) ZE3 fusion to the IgG N-terminus; 2) removal of the IgG light chain or Fab regions; 3) addition of hexamer-inducing mutations in the IgG Fc; 4) adding a self-binding epitope tag to create recombinant immune complexes (RIC); or 5) producing IgG fusions in plants that lack plant-specific β1,2-linked xylose and α1,3-linked fucose N-linked glycans. We also characterized the expression, solubility, and stability of the IgG fusions. By optimizing the size of polymeric constructs, a potently immunogenic vaccine candidate with improved solubility and high stability was produced at 1.5 milligrams IgG fusion per gram leaf fresh weight (mg/g LFW). In mice, the various IgG fusions elicited high titers of Zika-specific antibodies using only two doses without adjuvant, up to 150-fold higher antibody titers than ZE3 alone. We anticipate these findings will be broadly applicable to the creation of vaccines and antibody-based therapeutics.HighlightsAntigen immunogenicity is improved up to 150-fold by fusion to plant-made IgGs.High serum IgG endpoint titers >1:500,000 were achieved with only two doses without adjuvant.A modified immune complex has high expression, solubility, stability, and immunogenicity.

A New Vaccine Targeting the S1 of the S Protein Induce Mice Immune Response against COVID-19

“…As the coronavirus disease 2019 (COVID 19) is pandemic across the world, over 103 million cases of COVID 19 have been reported and more than 2 million people have been claimed. It is urgent to develop the vaccine of COVID 19 to help human get rid of the threat of it.…”

“…Several studies have demonstrated that IgG-based scaffold can enhance the solubility and stability of fusion protein, generating robust and long-lasting immune responses [18][19][20]. The fragment crystallizable (Fc) region is required for killing of virus-infected cells by complement-dependent cytotoxicity (CDC) and by antibodydependent cellular cytotoxicity (ADCC) [21,22].…”

A New Vaccine Targeting the S1 of the S Protein Induce Mice Immune Response against COVID-19

“…Several studies have demonstrated that IgG-based scaffold can enhance the solubility and stability of fusion protein, generating robust and long-lasting immune responses (18)(19)(20). The fragment crystallizable (Fc) region is required for killing of virus-infected cells by complement-dependent cytotoxicity (CDC) and by antibody-dependent cellular cytotoxicity (ADCC) (21,22).…”