Gamma-Irradiated Venezuelan Equine Encephalitis Vaccines

Abstract

The efficacy of Formalin-inactivated Venezuelan equine encephalitis (VEE) vaccine has been reported to be low for man. Although a live VEE vaccine has been shown to be highly effective for the protection of laboratory workers, local and systemic reactions have occurred in approximately 20% of inoculated individuals. Therefore, studies were initiated in an attempt to produce an inactivated vaccine of high potency with low toxicity. Inactivated VEE vaccines were prepared by exposing virus suspensions to 8 x 106 or 10 X 106 r of gamma radiation. Irradiated VEE vaccines prepared from virus suspensions produced in Maitland-type chick embryo (MTCE) cell cultures and in monolayer cultures of human diploid strain WI-38 cells were highly immunogenic for mice and guinea pigs. Guinea pigs vaccinated with a series of three inoculations of vaccine (MTCE) survived challenge with at least 108.4 mouse intracerebral 50% lethal doses of VEE virus. Irradiated vaccines induced high levels of serum-neutralizing and hemagglutinin-inhibiting antibodies in guinea pigs and rabbits. These findings suggest that ionizing radiation may be effective in the preparation of an inactivated VEE vaccine.

Immunogenicity of Purified Venezuelan Equine Encephalitis Virus Inactivated by Ionizing Radiation

“…The immunogenic potency of the nonviable vaccines described in this report is similar to that of other recently described VEE vaccines that were also inactivated by ionizing radiation (13). Those vaccines were evaluated by determination of the 50% effective dose (ED50), the quantity of undiluted vaccine protecting 50%" of tested animals from a lethal challenge.…”

“…The live, attenuated vaccine, although conferring good protection in man (7), causes a significant incidence of undesirable clinical manifestations (1). An experimental tissue culture vaccine inactivated by ionizing radiation was recently described (13).…”

Return of inactivated whole‐virus vaccine for superior efficacy

“…This rationale was soon incorporated into vaccine development, specifically for pathogens whose immunogenicity was destroyed by other means of inactivation. γ‐Irradiation was applied for the preparation of experimental vaccines against a number of infectious diseases, including parasitic ( Toxoplasma gondii , 88 Dictyocaulus viviparus , 89 Ancylostoma caninum , 90 Schistosoma japonicum , 91 , 92 Plasmodium berghei , 93 , 94 Trypanosoma congolense 95 and T. gondii ), 88 bacterial ( Escherichia coli , Pasteurella tularensis , 96 , 97 Mycobacterium tuberculosis 98 and Listeria monocytogenes ) 99 and viral diseases (bluetongue, 100 , 101 Venezuelan equine encephalitis, 102 , 103 rabies, 104 smallpox, 105 , 106 mumps 107 and influenza) 108 . Among these studies that have directly compared γ‐irradiation with other forms of inactivation methods, the superior retention of immunogenicity by γ‐irradiation has been consistently observed 104 , 109 , 110 , 111 …”

Immunity to Aerosol Challenge in Guinea Pigs Immunized with Gamma-Irradiated Venezuelan Equine Encephalitis Vaccines

“…Ten per cent or more of the animals were bled intracardially before vaccination, 21 days postvaccination, and 14 days postchallenge. Serum samples were assayed for hemagglutinatinginhibiting (HI; reference 14) and serum-neutralizing (SN) antibodies as previously described (15). SN indexes are expressed as log10 ; HI titers are expressed as the reciprocal.…”

“…MATERIALS AND METHODS Irradiated VEE vaccine. Three lots of irradiated vaccine were prepared from suspensions of VEE virus grown in human diploid cell monolayers (WI-38) as described previously (15). Seed virus used for preparation of vaccines had been passaged 14 times in chick embryos and once in WI-38 cell monolayers.…”