Isolation and characterization of new human carrier peptides from two important vaccine immunogens. Issue 10 (28th February 2020)

• Record Type: Journal Article
• Authors: Wantuch, Paeton L.; Sun, Lina; LoPilato, Rachel K.; Mousa, Jarrod J.; Haltiwanger, Robert S.; Avci, Fikri Y.
• Is Part Of: Vaccine. Volume 38:Issue 10(2020)
• Page Start: 2315
• Page End: 2325
• Publication Date: 2020-02-28
• Subjects: CRM197 -- Tetanus toxoid -- MHC class II -- T cell -- B cell -- Glycoconjugate vaccines -- Carrier protein; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2020.01.065
• Languages: English
• ISSNs: 0264-410X

Abstract

Highlights: We identified 11 MHCII-binding peptides generated from processing of TT and CRM197. Each peptide is capable of stimulating human CD4+ T cells. Donors have MHCII allelic repertoire that covers a wide range of the US population. These peptides may serve as carriers for future glycoconjugate vaccine strategies. Abstract: In the preparation of glycoconjugate vaccines in clinical practice, two highly immunogenic carrier proteins, CRM197 and tetanus toxoid (TT), are predominantly conjugated with the capsular polysaccharides (CPSs) of bacterial pathogens. In addition, TT has long been used as an effective vaccine to prevent tetanus. While these carrier proteins play an important role in immunogenicity and vaccine design alike, their defined human major histocompatibility complex class II (MHCII) T cell epitopes are inadequately characterized. In this current work, we use mass spectrometry to identify the peptides from these carrier proteins that are naturally processed and presented by human B cells via MHCII pathway. The MHCII-presented peptides are screened for their T cell stimulation using primary CD4+ T cells from four healthy adult donors. These combined methods reveal a subset of eleven CD4+ T cell epitopes that proliferate and stimulate human T cells with diverse MHCII allelic repertoire. Six of these peptides stand out as potential immunodominant epitopes by responding in three or more donors. Additionally, we provide evidence of these natural epitopes eliciting more significant T cell responses in donors than previously published TT peptides selected from T cell epitope screening. This study serves toward understanding carrier protein immune responses and thus enables the use of these peptides in developing novel knowledge-based vaccines to combat persisting problems in glycoconjugate vaccine design.