82 AN INTRODUCTION TO THE STUDY OF VIRUSES 
vaccines for dog distemper and equine encephalomyelitis has been 
found most satisfactory, but for fowl plague phenol is superior to 
formaldehyde. 
A vaccine prepared from inactivated rickettsiae has been used for a 
number of years against the Rocky Mountain spotted fever. The 
vaccine is prepared from the infected ticks which are the vectors of 
the disease and each ml of vaccine contains the inactivated virus from 
1} ticks. The ticks are raised in vast numbers, and infected adult ticks 
can be stored satisfactorily under refrigeration for at least 14 years 
before being used for vaccine manufacture. 
It is interesting to find that an increasing amount of potent vaccine 
was due to the use of old infective ticks, since the virus in aged ticks 
seems to have better antigenic properties (Parker, 1941). 
The use of vaccines containing active virus has had success with 
some virus diseases, such as fowl-pox, laryngo-tracheitis of chicken, 
and ovine ecthyma of sheep and goats. In these cases immunity is 
obtained by the administration of the active virus by unnatural or 
non-infective routes. Some viruses are infective only if introduced 
into the body by some particular portal of entry. Thus influenza 
virus must gain access to the respiratory tract in order to initiate the 
disease. If the virus is inoculated subcutaneously or intraperitoneally 
into ferrets or mice, no sign of illness follows, but a considerable 
degree of resistance against subsequent infection is established. De- 
pending upon this, American workers have practised human vacci- 
nation with active virus given subcutaneously (Wilson Smith, 1939). 
The greatest success by far, however, has been obtained by the use - 
of modified virus vaccines, the classical case of this technique being 
vaccination against smallpox carried out by Jenner, a hundred years 
before the discovery of the first virus. He used the virus of vaccinia, 
obtained from calves suffering from cowpox, which is a mutant or 
modified form of the smallpox virus and is non-virulent, remaining 
localized round the site of inoculation. It nevertheless stimulates the 
production of antibodies effective against the more virulent and 
invasive virus of smallpox. 
By different techniques, mutants of some viruses can now be pro- 
duced artificially. There are two main methods: (1) by propagation 
of the virus in animals which are not the natural hosts, and (2) by 
culturing the virus on the chorioallantoic membrane of the developing 
hen’s egg. 
Perhaps the most striking instance of vaccination with a modified 
