June 6-11, 2010
Matrivax R&D Corp. is a start-up biotechnology company with R&D operations located in Boston, USA and a vaccine pilot facility in Haikou, China. We are developing a proprietary vaccine process that entraps polysaccharides in a cross-linked protein ‘carrier’ or matrix, termed Protein Capsular Matrix Vaccine (PCMV), as an alternative to conjugate vaccine technology. Despite highly efficacious pneumococcal vaccines such as Prevnar®, S. pneumoniae causes > 1 million deaths worldwide annually. Likewise, typhoid fever afflicts ~16 million people, resulting in 600,000 deaths despite effective vaccines such as Typhim Vi® and Ty21a. The premise is that inexpensive,efficacious polysaccharide vaccines that elicit TH-cell ‘memory’ will actively displace their unconjugated and conjugated vaccine counterparts. Towards this end, Matrivax is actively research and developing pneumococcal, enteric fever, and meningococcal PCMV candidates.
In preliminary studies, a pneumococcal capsular polysaccharide (PPS) 14 ‘whole reaction’ PCMV employing ‘unoptimized chemistry’ elicited an anti-PPS14 reciprocal IgG antibody titer of ~7,000. Functional antibodies were elicited as evidenced by anti-sera facilitated opsonization and passively transferred antibodies conferring protection against lethal pneumococcal challenge. Recently Matrivax devised ‘optimized’ PCMV chemical reaction conditions improving polysaccharide incorporation into protein matrices as well as separated ‘whole reaction’ PCMV by size-exclusion chromatography yielding ‘size-fractionated’ PCMV particles. Size fractionated PPS14 PCMVs and Prevnar® were used to immunize mice in a three dose, bi-weekly regimen. Particle sized PCMV containing 0.12 and 0.03 ug PPS14 elicited anti-PPS14 reciprocal antibody GMT of 617,077 and 501,103,respectively, compared to Prevnar® (2 ug PPS14) which elicited a titer of 776,047. Thus, optimized PCMVs containing 1.5% or 6% the amount of PPS14 contained in Prevnar® elicited a comparable anti-PPS14 antibody response.
Matrivax next evaluated PCMV’s applicability to Vi antigen. SDS-PAGE data demonstrated that Vi was captured in a DNI matrix and capture ELISA further indicated that Vi antigen was localized at the surface of PCMV particles. Size fractionated Vi-DNI PMCV was compared to Typhim Vi® following a three dose, bi-weekly vaccine regimen in a murine immunogenicity study. Ten (10) ug Typhim Vi elicited an anti-Vi reciprocal antibody GMT of 200 whereas size-fractionated PCMVs containing ~2 ug Vi elicited an anti-Vi antibody GMT of >600. A Vi PCMV Phase 1 clinical trial is scheduled for 2Q11.
Kevin P. Killeen, Ann Thanawastien, and Tom Griffin, "DEVELOPMENT OF PROTEIN CAPSULAR MATRIX VACCINE (PCMV) TECHNOLOGY" in "Vaccine Technology III", John G. Auniņš,Merck, USA; Barry C. Buckland, BiologicB, USA; Kathrin U. Jansen, Pfizer, USA; Paula Marques Alves, IBET, Portugal Eds, ECI Symposium Series, (2010). http://dc.engconfintl.org/vaccine_iii/28