Gamma-irradiated rotavirus: A possible whole virus inactivated vaccine

Abstract

Rotavirus (RV) causes significant morbidity and mortality in developing countries, where children and infants are highly susceptible to severe disease symptoms. While live attenuated vaccines are available, reduced vaccine efficacy in developing countries illustrates the need for highly immunogenic alternative vaccines. Here, we studied the possible inactivation of RV using gamma(γ)-irradiation, and assessed the sterility and immunogenicity of γ-irradiated RV (γ-RV) as a novel vaccine candidate. Interestingly, the inactivation curve of RV did not show a log-linear regression following exposure to increased doses of γ-rays, and consequently the radiation dose required to achieve the internationally accepted Sterility Assurance Level could not be calculated. Nonetheless, we performed sterility testing based on serial passages of γ-RV, and our data clearly illustrate the lack of infectivity of γ-RV preparations irradiated with 50 kGy. In addition, we tested the immunogenicity of 50 kGy γ-RV in mice and our data illustrate the induction of strong RV-specific neutralising antibody responses following administration of γ-RV without using adjuvant. Therefore, whilst γ-RV may not constitute a replacement for current RV vaccines, this study represents a proof-of-concept that γ-irradiation can be applied to inactivate RV for vaccine purposes. Further investigation will be required to address whether γ-irradiation can be applied to improve safety and efficacy of existing live attenuated vaccines.

Innate and Adaptive Immune Responses against Bordetella pertussis and Pseudomonas aeruginosa in a Murine Model of Mucosal Vaccination against Respiratory Infection

“…Sometimes considered crude, whole cell vaccines (WCV) are often highly efficacious for the prevention of infection by pathogens and are often the first generation of vaccines to be developed when a pathogen emerges as a threat. WCVs are produced from cultured bacteria or viruses, either killed, inactivated, or attenuated by treatments such as gamma irradiation, heat, or chemicals [ 13 , 14 , 15 , 16 , 17 ]. These preparations contain immunostimulatory endotoxin and a wide array of antigens.…”

Controlling the Colonization of Clostridium perfringens in Broiler Chickens by an Electron-Beam-Killed Vaccine

“…The benefits of developing vaccines using eBeam technology are that it is chemical-free, highly scalable, and can be very precise in delivering the eBeam doses as well as assure complete inactivation of large volume lots. Presently, several irradiated viral and bacterial vaccines have been developed that have been shown to be more efficacious than other vaccines prepared by other technologies [ 57 , 58 , 59 , 60 , 61 , 62 ]. Electron beam technology platforms are continually improving in terms of robustness, modularity, and versatility in terms of beam power and electron energies [ 63 ].…”

Sterility of gamma-irradiated pathogens: a new mathematical formula to calculate sterilizing doses

“…RV was titrated by focus-forming assay (FFA) as described previously [ 29 ]. Briefly, MA104 cells were seeded in 96-well flat-bottomed microtitre plates at 6.4 × 10 3 cells/well and plates were incubated at 37°C for 3 days until a confluent monolayer had formed.…”

“…Our recent publications, however, have shown non-linear inactivation curves ( Fig. 1B ) for rotavirus (RV) [ 29 ] and S. pneumoniae [ 30 ], demonstrating multiple-hit kinetics for complicated pathogens. While a D 10 value is usually calculated based on the linear portion of the curve [ 22 ], ignoring the shoulder of resistance could lead to miscalculation of the irradiation dose required to achieve a SAL of 10 −6 (or DS SAL ).…”