DISIlTTEGRATIOir OP VIRUSES 



43 



The hemagglutinin of the virus is thus at its maximum stability in solutions much 

 more alkaline than the isoelectric point. 



iiecause of the fact that many viruses seem to denature or to become inacti- 

 vated at rates which vary with the initial virus concentration, it was thought 

 worthwhile to determine whether or not the rate of inactivation of influenza virus 

 hemagglutinin varies with the initial concentration. The data shown in Table V 

 Indicate that the reaction velocity for the destruction of hemagglutinin increases 

 as one decreases the concentration of virus. 



TABLE V 

 REACTIO N VELOCITY C0N5TA1TTS FOR THERMAL IITACTIVATION OF CCA OP IHPLUEITZA A VIRUS 



If^ 



kVo 



"58^" 



kV, 



isr^ 



kV^ 



However, it can be seen further that if one multiplies the reaction rate by the 

 square root of the initial virus concentration, one obtains values which do not 

 vary in any orderly manner. This would seem to indicate that the reaction rate 

 is inversely proportional to the square root of initial virus concentration. An 

 explanation for this behavior can be found. As was pointed out previously, the 

 fact that the destruction of hemagglutinin seems to be a reaction of the three 

 halves order, when it should be, in fact, a reaction of the first order, can be 

 explained by the assumption that the hemagglutinin is inhomogeneous with respect 

 to its stability. If one supposes that there are at least two different kinds 

 of hemagglutinin present, that each is destroyed according to a first order re- 

 action, and that the overall destruction of the two or more types is such as to 

 make the reaction appear to be one of the three halves order, then one can show 

 from simple kinetic considerations that the apparent reaction velocity constant 

 calculated on the assumption that the reaction really is of the three halves 

 order will vary with the reciprocal of the square root of the initial total virus 

 concentration. Since this is what does happen, one is justified in considering 

 the dependence of rate of destruction upon the reciprocal of square root of in- 

 itial concentration as evidence in favor of the complexity of the hemagglutinin. 



This question of the destruction of influenza A virus hemagglutinin has 

 its practical aspect. A vaccine has been developed for influenza virus. I'he 

 vaccine is nothing more than a suspension of the virus which has been rendered 

 non-infectious with formaldehyde. This vaccine is prepared by biological houses 

 and stored until used by a physician. It is very important to know the optimal 

 conditions for storage. What one wants to know is the condition of storage at 

 which the vaccine will lose its ability to form antibodies most slowly. When 

 one studies the rate of destruction of hemagglutinin, one might well provide 

 clues for establishing the conditions most favorable for storage of influenza 

 vaccine . 



