Pw. Tebbey et al., Effective mucosal immunization against respiratory syncytial virus using purified F protein and a genetically detoxified cholera holotoxin, CT-E29H, VACCINE, 18(24), 2000, pp. 2723-2734
We exploited the powerful adjuvant properties of cholera holotoxin (CT) to
create a mucosally administered subunit vaccine against respiratory syncyti
al virus (RSV). A genetically detoxified mutant CT with an E to H substitut
ion at amino acid 29 of the CT-Al subunit (CT-E29H) was compared to wild ty
pe CT for toxicity and potential use as an intranasal (IN) adjuvant for the
natural fusion (F) protein of RSV, When compared to CT the results demonst
rated that: (1) CT-E29H binding to GM1 ganglioside was equivalent, (2) ADP-
ribosylation of agmatine was 11.7%, and (3) toxicity was attenuated in both
Y-1 adrenal (1.2%) and patent mouse gut weight assays. IN vaccination with
F protein formulated with CT-E29H induced serum anti-CT and anti-F protein
antibodies that were comparable to those obtained after vaccination with e
quivalent doses of CT. Vaccinations containing CT-E29H at doses of 0.1 mu g
were statistically equivalent to 1.0 mu g in enhancing responses to F prot
ein. Antigen-specific mucosal IgA and anti-RSV neutralizing antibodies were
detected in nasal washes and sera, respectively, of mice that had received
F protein and 0.1 or 1.0 mu g of CT-E29H. Anti-F protein IgA was not detec
ted in the nasal washes from mice IN vaccinated with 0.01 mu g CT-E29H or I
M with F protein adsorbed to AlOH adjuvant. In addition, the formulation of
purified F protein and CT-E29H (0.1 and 1.0 mu g) facilitated protection o
f both mouse lung and nose from live RSV challenge. Collectively, the data
have important implications for vaccine strategies that use genetically det
oxified mutant cholera holotoxins for the mucosal delivery of highly purifi
ed RSV antigens. (C) 2000 Elsevier Science Ltd. Ail rights reserved.