VIRUSES 60 



• 

 again threaten, because death usually Is the result of complications such as- 

 pneumonia following the attack of influenza. The methods available for combat- 

 ing pneumonia probably are adequate to insure against a repetition of the ter- 

 rific death toll. Nevertheless influenza is a serious disease which, even when 

 it does not kill, completely disables its victims for a period of one to four 

 weeks. It takes little imagination to picture the consequences of an influenza 

 epidemic in an active military theater. It was an urgent war problem to develop 

 a satisfactory influenza vaccine. It will be remembered that the second way of 

 vaccinating is to introduce into the body of the host a large amount of suspen- 

 sion of virus rendered incapable of multiplying and producing disease, but not 

 incapable of inducing the formation in the blood of antibodies. Vaccination a- 

 galnst influenza is of this type. As a result of fundamental biological studies 

 in influenza virus carried out in several laboratories, and of chemical and 

 physical studies carried out at the Hockefeller Institute for lledical Research, 

 two types of influenza vaccine were developed during the war. Both have been 

 used to immunize the members of our armed forces and both are now available for 

 civilian use. iioth of these vaccines are composed of suspensions of influenza 

 virus to which an amount of formaldehyde has been added, sufficient to destroy 

 the ability to induce antibody formation. 



The virus subsequently to be used as vaccine is grown in chicken embryos. 

 Ten-day old chicken embryos or half-hatched eggs are inoculated with influenza 

 virus. This is done by simply punching a hole in the shell above the air sack 

 and introducing a hypodermic needle into the fluids surrounding the embryo. Dur- 

 ing the course of 48 hours the virus multiplies and causes a disease in the em- 

 bryo. The virus is then liberated into the fluids. When the embryo is chilled, 

 these fluids can be removed. The virus is then recovered and is treated with 

 formaldehyde to form the vaccine. The two vaccines at present available differ 

 with respect to the method used for the concentration of the virus. The vaccine 

 which was first accepted by the Army is purified and concentrated by precipi- 

 tation with chicken red blood cells. The precipitated red blood cell-virus com- 

 plex is suspended in a small volume of salt solution and then heated up to body 

 temperature. At this temperature the virus dissociates from the cells. The red 

 cells can be removed by low speed centrifugation . Formaldehyde is then added to 

 the virus to destroy its ability to reproduce. This material is distributed as 

 vaccine. The second type of vaccine was developed as a result of the fundamental 

 physical and chemical studies on the nature of influenza virus carried out at the 

 Hockefeller Institute for Medical Research. In this particular case, the fluids 

 obtained from the diseased chicken embryos are subjected to high speed centri- 

 fugation with a Sharpies Supercentrifuge - a device very much resembling an or- 

 dinary cream separator. The formaldehyde used to inactivate the virus is added 

 to the fluid before centrifugation. The inactivated virus collects on the peri- 

 phery of the centrifuge in a mass. This can be suspended in a small volume of 

 salt solution. The centrifugation process seems to give a somewhat higher de- 

 gree of concentration of the virus and produces a product which causes a low 

 incidence of unfavorable reactions in the vaccinated person. There are two kinds 

 of Influenza recognized today, influenza A and influenza B. Immunity to influ- 

 enza A does not protect against influenza B and conversely. Therefore influenza 

 vaccines are mixtures of both influenza A and influenza B viruses. 



The vaccine solution is administered by subcutaneous injection. When the 

 centrifuged vaccine is used, about 3/10 of a milligram of virus is used as a 

 dose. This represents about half of the material that can be obtained from the 

 fluids of a single infected chicken embryo. An individual thus vaccinated pro- 

 duces antibodies to influenza. This can be demonstrated in the laborato.ry, for 

 the serum from a vaccinated individual will neutralize virus in a test tube. 

 This antibody formation is associated with protection against the virus disease. 

 Henle, Henle and Stokes showed that hximan volunteers who had been vaccinated 

 in this manner showed a much lower susceptibility to experimental influenza than 

 nonvaccinated individuals. The Influenza Commission of the U. S. Army conducted 

 a large scale test of the effectiveness of the influenza vaccine. I>uring the 



