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


METHODS
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.


CONCLUSIONS
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.
a Pfizer Vaccine Immunotherapeutics , Ottawa Laboratories , Ottawa , ON , Canada ;
Michael J
MJ
McCluskie
a Pfizer Vaccine Immunotherapeutics , Ottawa Laboratories , Ottawa , ON , Canada ;
Dana M
DM
Evans
a Pfizer Vaccine Immunotherapeutics , Ottawa Laboratories , Ottawa , ON , Canada ;
Ningli
N
Zhang
a Pfizer Vaccine Immunotherapeutics , Ottawa Laboratories , Ottawa , ON , Canada ;
Michelle
M
Benoit
b Pfizer Vaccine Research and Early Development , Pearl River , NY , USA ;
Susan P
SP
McElhiney
b Pfizer Vaccine Research and Early Development , Pearl River , NY , USA ;
Manu
M
Unnithan
c Pfizer Biotherapeutics Pharmaceutical Sciences , St. Louis , MO , USA ;
Suzanne C
SC
DeMarco
d Pfizer Vaccine Immunotherapeutics , La Jolla , CA , USA.
Bryan
B
Clay
d Pfizer Vaccine Immunotherapeutics , La Jolla , CA , USA.
Christoph
C
Huber
c Pfizer Biotherapeutics Pharmaceutical Sciences , St. Louis , MO , USA ;
Aparna
A
Deora
c Pfizer Biotherapeutics Pharmaceutical Sciences , St. Louis , MO , USA ;
Jennifer M
JM
Thorn
d Pfizer Vaccine Immunotherapeutics , La Jolla , CA , USA.
David R
DR
Stead
d Pfizer Vaccine Immunotherapeutics , La Jolla , CA , USA.
James R
JR
Merson
a Pfizer Vaccine Immunotherapeutics , Ottawa Laboratories , Ottawa , ON , Canada ;
Heather L
HL
Davis
D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry / Q000276:immunology*; D005260:Female; D006241:Haptens / Q000737:chemistry / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009538:Nicotine / Q000737:chemistry / Q000276:immunology*
D001426:Bacterial Proteins; D006241:Haptens; C028581:CRM197 (non-toxic variant of diphtheria toxin); D009538:Nicotine
Adjuvant; immune response; immunization; mice; pharmacology