The effect of preexisting anti-carrier immunity on subsequent responses to CRM197 or Qb-VLP conjugate vaccines. (3rd May 2016)

• Record Type: Journal Article
• Authors: McCluskie, Michael J.; Evans, Dana M.; Zhang, Ningli; Benoit, Michelle; McElhiney, Susan P.; Unnithan, Manu; DeMarco, Suzanne C.; Clay, Bryan; Huber, Christoph; Deora, Aparna; Thorn, Jennifer M.; Stead, David R.; Merson, James R.; Davis, Heather L.
• Is Part Of: Immunopharmacology and immunotoxicology. Volume 38:Number 3(2016:Jun.)
• Page Start: 184
• Page End: 196
• Publication Date: 2016-05-03
• Subjects: Adjuvant -- immune response -- immunization -- mice -- pharmacology; Immunopharmacology -- Periodicals; Immunotoxicology -- Periodicals; Antibody-toxin conjugates -- Periodicals; Immunology -- Periodicals; 615.37
• DOI: 10.3109/08923973.2016.1165246
• Languages: English
• ISSNs: 0892-3973

Abstract

Abstract: Context: Certain antigens, such as haptens (small molecules), short peptides, and carbohydrates (e.g. bacterial polysaccharides) are non- or poorly immunogenic unless conjugated to a carrier molecule that provides a structural scaffold for antigen presentation as well as T cell help required for B-cell activation and maturation. However, the carriers themselves are immunogenic and resulting carrier-specific immune responses may impact the immunogenicity of other conjugate vaccines using the same carrier that are administered subsequently. Objective: Herein, using two different carriers (cross-reactive material 197, CRM and Qb-VLP), we examined in mice the impact that preexisting anti-carrier antibodies (Ab) had on subsequent immune responses to conjugates with either the same or a different carrier. Method: For this purpose, we used two nicotine hapten conjugates (NIC7-CRM or NIC-Qb), two IgE peptide conjugates (Y-CRM or Y-Qb), and a pneumococcal polysaccharide conjugate (Prevnar 13 ® ). Results: Prior exposure to CRM or Qb-VLP significantly reduced subsequent responses to the conjugated antigen having the homologous carrier, with the exception of Prevnar 13® where anti-polysaccharide responses were similar to those in animals without preexisting anti-carrier Ab. Conclusion: Collectively, the data suggest that the relative sizes of the antigen and carrier, as well as the conjugation density for a given conjugate impact the extent of anti-carrier suppression. All animals developed anti-carrier responses with repeat vaccination and the differences in Ab titer between groups with and without preexisting anti-carrier responses became less apparent; however, anti-carrier effects were more durable for Ab function.