A mutant pertussis toxin molecule that lacks ADP-ribosyltransferase activity, PT-9K/129G, is an effective mucosal adjuvant for intranasally delivered proteins

• DOI: 10.1128/iai.63.6.2100-2108.1995
• Publication Date: 2020-01-06T18:49:08Z
• Authors: M Roberts; A Bacon; R Rappuoli; M Pizza; I Cropley; G Douce; G Dougan; M Marinaro; J McGhee; S Chatfield
• Keywords: Cholera toxin; Diphtheria Toxin; Toxoid

We examined the capacity of a genetically detoxified derivative pertussis toxin (PTX), PT-9K/129G, to act as mucosal adjuvant for an intranasally (i.n.) administered tetanus vaccine. Groups mice were immunized i.n. with nontoxic C-terminal 50-kDa portion (fragment C [Frg C]) either alone or mixed PTX, cholera (CT) subcutaneously (s.c.) equivalent amount Frg adsorbed alhydrogel. In response single immunization, receiving plus PT-9K/129G CT and parenterally developed high-titer (> 20,000) anti-Frg antibodies, whereas PTX seroconverted only after being boosted. The serum was dominated by immunoglobulin G1 (IgG1) in s.c. contrast, IgG1, IgG2a, IgG2b contributed almost equally when adjuvant. Anti-Frg IgE detected sera High levels IgA antibodies present nasal lavage fluid from but not that given parenterally. adjuvanticity manifested inbred well outbred mice. A dose (with high specific activity) sufficient protect all challenge, contrast case received conclude analog which is devoid ADP-ribosyltransferase activity, potent vaccines delivered via respiratory tract.