LT-IIb(T13I), a non-toxic type II heat-labile enterotoxin, augments the capacity of a ricin toxin subunit vaccine to evoke neutralizing antibodies and protective immunity.
Currently, there is a shortage of adjuvants that can be employed with protein subunit vaccines to enhance protection against biological threats. LT-IIb(T13I) is an engineered nontoxic derivative of LT-IIb, a member of the type II subfamily of heat labile enterotoxins expressed by Escherichia coli, that possesses potent mucosal adjuvant properties. In this study we evaluated the capacity of LT-IIb(T13I) to augment the potency of RiVax, a recombinant ricin toxin A subunit vaccine, when co-administered to mice via the intradermal (i.d.) and intranasal (i.n.) routes. We report that co-administration of RiVax with LT-IIb(T13I) by the i.d. route enhanced the levels of RiVax-specific serum IgG antibodies (Ab) and elevated the ratio of ricin-neutralizing to non-neutralizing Ab, as compared to RiVax alone. Protection against a lethal ricin challenge was also augmented by LT-IIb(T13I). While local inflammatory responses elicited by LT-IIb(T13I) were comparable to those elicited by aluminum salts (Imject®), LT-IIb(T13I) was more effective than aluminum salts at augmenting production of RiVax-specific serum IgG. Finally, i.n. administration of RiVax with LT-IIb(T13I) also increased levels of RiVax-specific serum and mucosal Ab and enhanced protection against ricin challenge. Collectively, these data highlight the potential of LT-IIb(T13I) as an effective next-generation i.d., or possibly i.n. adjuvant for enhancing the immunogenicity of subunit vaccines for biodefense.
The Witebsky Center for Microbial Pathogenesis and Immunology, The University at Buffalo, Buffalo, New York, United States of America.
Christopher J
CJ
Greene
Chrystal M
CM
Chadwick
Lorrie M
LM
Mandell
John C
JC
Hu
Joanne M
JM
O'Hara
Robert N
RN
Brey
Nicholas J
NJ
Mantis
Terry D
TD
Connell
D000276:Adjuvants, Immunologic; D000281:Administration, Intranasal; D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology* / Q000627:therapeutic use; D001427:Bacterial Toxins / Q000008:administration & dosage* / Q000276:immunology / Q000378:metabolism; D004357:Drug Synergism; D004768:Enterotoxins / Q000008:administration & dosage* / Q000276:immunology / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000008:administration & dosage* / Q000276:immunology / Q000378:metabolism; D005260:Female; D018928:Immunity, Mucosal; D007114:Immunization; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D012867:Skin / Q000276:immunology* / Q000378:metabolism; D014612:Vaccines / Q000008:administration & dosage* / Q000276:immunology / Q000378:metabolism; D022223:Vaccines, Subunit / Q000627:therapeutic use*; D014614:Vaccines, Synthetic / Q000627:therapeutic use*
D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D001427:Bacterial Toxins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; C509236:RiVax; D014612:Vaccines; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic; C027538:heat-labile enterotoxin, E coli