Subunit Vaccine against the Seven Serotypes of Botulism

Enhancing the Protective Immune Response against Botulism

“…This suggests that neutralizing capacity for BoNT intoxication need not parallel potency to neutralize HCR-receptor interactions. While recombinant HCRs are candidate BoNT vaccines, each variant retains an ability to bind and enter neurons that is similar to that of the native holotoxin (29,33,42), and possible physiological consequences of recombinant HCRs entering motor neurons are unknown. By eliminating receptor binding, HCR/A retains its protective ability and even appears to be a more protective immunogen than wild-type HCR while eliminating chance side effects and sequestration from immune detection.…”

“…This vaccine is currently in early clinical trials; passive immunization in animal models from neutralizing antibodies generated in humans improved survival with BoNT challenges (32). Previously, our lab engineered a vaccine composed of the HCR domains of each of the seven BoNT serotypes which protected against challenge by each respective holotoxin (33). A lack of cross-neutralization is consistent with the observation that immunoreactive epitopes appear to be distinct for different serotypes, as reported for BoNT/A and BoNT/B (30,34).…”

Binding activity and immunogenic characterization of recombinant C-terminal quarter and half of the heavy chain of botulinum neurotoxin serotype A

“…28,29 Ganglioside, especially GT1b, is considered a component of the double-receptor system of BoNTs. 24,[30][31][32] The first step in BoNT/A intoxication of neurons starts with binding of C-terminus subdomain of Hc to ganglioside on presynaptic membranes.…”

“…Ganglioside binding assays were performed following the procedure described previously by modified method. 6,28,38 ELISA plates were coated with 100 μl of 40 μg/ml bovine ganglioside GT1b (Sigma) per well and blocked with PBS containing 1% Casein (Sigma) at 25°C for 3 h. After incubation, the wells were washed with PBST and then 100 μl of purified AHc (50 μg/ml), 35 AHc-C (50 μg/ml) and BSA (50 μg/ml) were added to different wells for 3 h at 25°C. BSA was used as negative control.…”

Vaccines against botulism

“…These studies showed the feasibility of producing HC as a protein-derived vaccine candidate and encouraged the continued development of the vaccine potential of HC in several heterologous expression systems [52][53][54][55]. Only a few examples towards developing HC as a vaccine will be described and interested readers are encouraged search for other studies that utilize HCs for vaccine development.…”