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.
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 pneumococcalpolysaccharide 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.
Authors: Wenbo Jiang; Emily H Pilkington; Hannah G Kelly; Hyon-Xhi Tan; Jennifer A Juno; Adam K Wheatley; Stephen J Kent Journal: PLoS One Date: 2020-11-02 Impact factor: 3.240
Authors: Cyrielle Fougeroux; Louise Goksøyr; Manja Idorn; Vladislav Soroka; Sebenzile K Myeni; Robert Dagil; Christoph M Janitzek; Max Søgaard; Kara-Lee Aves; Emma W Horsted; Sayit Mahmut Erdoğan; Tobias Gustavsson; Jerzy Dorosz; Stine Clemmensen; Laurits Fredsgaard; Susan Thrane; Elena E Vidal-Calvo; Paul Khalifé; Thomas M Hulen; Swati Choudhary; Michael Theisen; Susheel K Singh; Asier Garcia-Senosiain; Linda Van Oosten; Gorben Pijlman; Bettina Hierzberger; Tanja Domeyer; Blanka W Nalewajek; Anette Strøbæk; Magdalena Skrzypczak; Laura F Andersson; Søren Buus; Anette Stryhn Buus; Jan Pravsgaard Christensen; Tim J Dalebout; Kasper Iversen; Lene H Harritshøj; Benjamin Mordmüller; Henrik Ullum; Line S Reinert; Willem Adriaan de Jongh; Marjolein Kikkert; Søren R Paludan; Thor G Theander; Morten A Nielsen; Ali Salanti; Adam F Sander Journal: Nat Commun Date: 2021-01-12 Impact factor: 14.919
Authors: Essie Komla; Oscar B Torres; Rashmi Jalah; Agnieszka Sulima; Zoltan Beck; Carl R Alving; Arthur E Jacobson; Kenner C Rice; Gary R Matyas Journal: Vaccines (Basel) Date: 2021-06-01