Viral antigens for human and veterinary vaccines are still inactivated with formaldehyde. This is not an ideal inactivant and the problems of formaldehyde inactivation of vaccines are discussed. Vaccines inactivated with aziridines are superior in safety and antigenicity. Aziridines inactivate viruses in a first-order reaction and the inactivation rate and endpoint can be determined. The preparation and application of the aziridine compound binary ethylenimine (BEI) and the necessary conditions for and controls of the inactivation process are described and discussed. A computer program has been written for assistance in the use of BEI for controlled inactivation of viral antigens.

Foot-and-mouth disease virus was inactivated with binary ethylenimine formed apart from or directly in the virus suspension by the cyclization of 2-bromoethylamine hydrobromide or 2-chloroethylamine hydrochloride under alkaline conditions. The inactivation rates with binary ethylenimine prepared apart from the virus suspension in dilute sodium hydroxide with either 2-bromoethylamine hydrobromide or 2-chlorethylamine hydrochloride were higher than with pure ethylenimine. When binary ethylenime was prepared directly in the virus suspension only 2-bromoethylamine hydrobromide gave acceptable inactivation rates. The reduced inactivation rates for binary ethylenimine directly prepared in the virus suspension are due to the different cyclization rates of 2-bromoethylamine hydrobromide and 2-chloroethylamine hydrochloride and to the interference of bicarbonate in the cyclization reaction. The complement fixing antigen of foot-and-mouth disease virus was not affected by binary ethylenimine inactivation. Vaccines prepared with foot-and-mouth disease virus inactivated by binary ethylenimine were comparable in their immunogenicity to vaccines prepared with ethylenimine or N-acetylethylenimine used as inactivants. Application of binary ethylenimine in the preparation of foot-and-mouth disease vaccines considerably reduces the potential danger associated with handling pure ethylenimine and other aziridines.

Summary The inactivation of foot‐and‐mouth disease virus by ethylenimine and propylenimine has been compared to inactivation by N‐acetylethylenimine. Propylenimine has an inactivation rate similar to N‐acetylethylenimine. Ethylenimine has a higher inactivation rate and unaltered activity upon storage at room temperature for extended periods of time and is therefore a more desirable inactivant for this virus than N‐acetylethylenimine. Zusammenfassung Die Inaktivierung von Maul‐ und Klauenseuchevirus durch Äthylenimin und Propylenimin Die Inaktivierung von Maul‐ und Klauenseuchevirus durch Äthylenimin und Propylenimin wurde mit der Inaktivierung durch N‐acetyläthylenimin verglichen. Die Inaktivierungsrate von Propylenimin ist der von N‐acetyläthylenimin ähnlich. Äthylenimin hat eine höhere Inaktivierungsrate und eine unveränderte Aktivität nach Lagerung bei Zimmertemperatur über längere Zeiträume und ist deshalb ein besseres Inaktivierungsmittel für das MKS‐Virus als N‐acetyläthylenimin. Résumé L'inactivation du virus de la fièvre aphteuse par éthylènimine et propylènimine On a comparé l'inactivation du virus de la fièvre aphteuse avec éthylènimine et propylènimine avec l'inactivation au moyen de N‐acéthyléthlènimine. L'indice d'inactivation est le même pour propylènimine et N‐acéthyl‐éthylènimine. Ethylènimine a montré un indice d'inactivation plus rapide et une activité inchangée après entreposage à la température ambiante à des temps plus longs; éthylènimine est un meilleur procédé d'inactivation pour le virus de la fièvre aphteuse que N‐acéthyléthylènimine. Resumen La inactivación del virus aftoso mediante etilenimina y propilenimina La inactivación del virus aftoso por medio de etilenimina y propilenimina se comparó con la inactivación mediante N‐acetiletilenimina. La tasa de inactivación de propilenimina es semejante a la apreciada utilizando N‐acetiletilenimina. La etilenimina arroja una tasa de inactivación más rápida y una actividad inalterable tras almacenamiento en el laboratorio a temperatura ambiente durante un espacio largo de tiempo y es un agente de inactivación mejor para el virus aftoso que la N‐acetiletilenimina.

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