Factors Influencing Inactivation of Infectivity and Hemagglutinin of Influenza Virus by Gamma Radiation

Abstract

Factors influencing the effects of gamma, irradiation on influenza A(PR8) virus suspensions have been investigated. In purified virus suspensions in physiological saline, the hemagglutinin was destroyed more rapidly than the infectivity. The addition of reagents such as histidine, sodium p-aminohippurate, ascorbic acid, or cystine to the saline suspension reversed this effect. It was also found that the effect of a given amount of gamma radiation on the infectivity and hemagglutinin was similar regardless of whether the radiation was administered as a single dose or as two or four divided doses on different days. It is possible to calculate the amount of radiation required to destroy the infectivity and yet retain most of the hemagglutinin content, If a given dose of radiation has been insufficient to produce complete virus inactivation, the suspension can be subjected to a further dose, the amount of which can be exactly calculated, without destroying the hemagglutinin. These experiments were repeated with other strains of influenza A and B with similar results. The application of this work to the preparation of virus vaccines is being investigated and will be reported later.

Return of inactivated whole‐virus vaccine for superior efficacy

“…Unsurprisingly, γ‐irradiation was also used for influenza virus vaccines. Polley and colleagues were one of the first to successfully prepare γ‐inactivated influenza virus vaccine 112 . Guinea pigs intraperitoneally immunized with γ‐inactivated A/PR8 (H1N1) induced high hemagglutination inhibition, and serum neutralization titres, conferring homologous protection.…”

“…The primary target of γ‐ray irradiation is the microbial genome 125 . It causes strand breaks in the genetic material, rendering the pathogen replication deficient without causing significant denaturation of the structures and biological function of proteins 108 , 112 , 133 , 134 , 135 , 136 . For this reason, γ‐ray inactivation has been used in studies of protein chemistry of highly virulent pathogens, such as Ebola, Marburg and Lassa virus, generating a relatively low risk of infection for the experimenter 137 , 138 .…”

The Use of Gamma Radiation for the Preparation of Virus Vaccines

“…This was a close about 50y0 greater than that calculated to be required from the inactivation curves (9). After it was shown that each virus suspension was non-infective (lo), each was inoculated into a group of six guinea pigs, in amounts of 0.5 n~l per aniii~al by the ii~traperitoneal route.…”

“…Jordan and Icempe (2) found that viruses could be inactivated with retention of antigenicity by performing the gamma irradiation on samples packed in dry ice. Recently it was shown in this Laboratory that, by the addition of various protective agents t o purified suspensions of influenza virus, it was possible to destroy the infectivity yet t o retain most of the hemagglutinin content (9). I t is the purpose of this paper t o report the application of this work to the preparatioil of influenza and mumps virus vaccines and the results obtained with these vaccines on inoculation into small laboratory animals.…”

“…The sediment was resuspencled in a quantity of physiological saline so as to produce a hemagglutination titer of about 1 :2560 1,er ml. Prior to irradiation, histidine to cive a con cent^-ation of 0.2% \vas added to the iiifluenza virus suspe~~sions since this reagent was shonrn previously to protect the I~emagglutinin cluring gamma irradiation (9). With mumps virus suspensioils, 0.2% soclium p-aininol~ippurate (l'-AH) was used as the protective agent.…”