Potential Novel and Superior Vaccines
...with the goal of precise, consistent and optimal conjugation.
60% Pneumococcus Vxs
25% Meningococcus Vxs
15% H Flu Vxs
Source: Industry reports and SEC filings
Conjugate vaccines consist of antigens (polysaccharides or oligosaccharides) that are chemically coupled to a protein carrier. Coupling of the saccharides to protein converts polysaccharides to T-dependent antigens, which elicit robust immune responses in infants and adults. These conjugate vaccines elicit T-cell help for B-cells that produce IgG antibodies to the conjugated polysaccharide1. Glycoconjugates thus induce PS-specific IgM-to-IgG switching, memory B-cell development, affinity maturation, and long-lived T-cell memory. Conjugate vaccines have played an enormous role in preventing infectious diseases caused by virulent pathogens such as H. influenzae, Streptococcus pneumoniae, and Neisseria meningitidis2-4.
Despite the successes to date, there are not only a significant number of additional bacterial strains that have yet to be incorporated into current conjugate vaccines, but also many infectious diseases that have yet to be addressed using this potent modality.
The XpressCF platform allows for efficient conjugation of antigens to precise positions on carrier proteins via the incorporation of multiple non-native amino acid (nnAA) substitutions to permit click chemistry attachment. This precise and robust technique results in homogeneous and consistent vaccines that may confer important immunological and clinical benefits relative to current conjugate vaccines. Pinpointing the placement of the antigen on the carrier has the potential to improve host immune responses by avoiding the discrete sites on the carrier responsible for T-cell help, which are often impinged by current conjugation methods. Furthermore, the precise optimization of antigen positioning on the carrier protein allows the attachment of multiple antigenic constructs to a single protein carrier, which may facilitate the production of broader-spectrum vaccines. These improvements may help us develop potential novel conjugate vaccines to deliver recognized immunity and broader protection and can both be more easily characterized and consistently produced as a result of our high-yield, streamlined and industrialized production process.
1. Editorial Review: Conjugate Vaccines. Goldblatt D. Clin Exp Immunol. 119: 1–3 (2000).
2. Preparation, characterization, and immunogenicity of Haemophilus influenzae type b polysaccharide-protein conjugates. Schneerson R, Barrera O, Sutton A, Robbins JB. J Exp Med. 152: 361– 376 (1980).
3. Predictors of pneumococcal conjugate vaccine immunogenicity among infants and toddlers in an American Indian PnCRM197 efficacy trial. O’Brien KL, Moisi J, Moulton LH, Madore D, Eick A, Reid R, Weatherholtz R, Millar E, Hu D, Hackell J, Kohberger R, Siber G, Santosham M. J Infect Dis. 196: 104-14 (2007).
4. Effectiveness of meningococcal serogroup C conjugate vaccine 4 years after introduction. Trotter C, Kaczmarski E, Miller E, Ramsay ME. The Lancet. 364: 24-30 (2004).