The effect of preexisting anti-carrier immunity on subsequent responses to CRM₁₉₇ or Qb-VLP conjugate vaccines

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.

Keywords:

• Adjuvant
• immune response
• immunization
• mice
• pharmacology

Acknowledgements

We are grateful to Nathalie Lengacher, Stephanie Ringrose, Tharsika Tharmanathan, Liana Medynski, and Oscar Maldonado for excellent technical assistance and to Peter Giardina for scientific discussion.

Disclosure statement

All authors were Pfizer employees when this work was conducted and all studies were financed by Pfizer.