262 T. FRANCIS, JR. 



influenza virus was the predominant strain during the period of 1915-24, 

 especially about 1918. In 1935, antibodies to PR8 were found in the first 

 years of life; in 1948, they were found first at the age of seven; in the 1952 sera 

 they were not measurable until eleven or twelve years of age. In 1935, 

 antibodies to swine virus were not found before eleven years of age; in 1952, 

 seventeen years later, they were first detected at twenty-nine years of age. 

 The shift of these antibodies temporally coincides remarkably with the 

 passage of time, and the age distribution of antibodies to the respective 

 prototypes thus constitutes a recapitulation of the periods of prevalence of 

 certain antigenic groups of type A virus. The same patterns have been 

 obtained in England, Japan, and Czechoslovakia (Davenport et ah, 1955; 

 Davenport and Hennessy, 1958; Blaskovic and Rathova, 1956). 



Recognition of these antibody patterns in the general population provides 

 epidemiological perspective to consideration of serological classification and 

 appears to define the significant variants among influenza A viruses. They 

 behave as major serological groups in which the lesser degrees of serological 

 variation from one year to another are indistinct. The data also afford 

 explanation for the variability and lack of strain specificity in antibody 

 response to infection or vaccination; existing antibodies to one group are 

 enhanced by subsequent experience with a related strain. High antibody 

 levels noted in the acute stage of infection are more likely then to be the 

 heterologous pre-existing antibody to one group, while that to the infecting 

 virus is low. 



c. Doctrine of Original Antigenic Sin. The dominant character of the group 

 antibodies is further emphasized by serological responses of different age 

 groups to vaccination. When children who have some antibody are vaccinated 

 with any of the A strains, they respond with antibodies to A-prime virus 

 strains; persons in the middle range respond with additional antibodies to the 

 PR8 group of viruses; people over thirty respond with increased antibody to 

 swine influenza virus (Davenport and Hennessy, 1956). Absorptions of sera 

 from groups of persons both normal and after vaccination resulted in complete 

 removal of antibody to all strains of influenza virus within a type when a 

 strain of antigenic configuration similar to that of the strain of first experience 

 was employed (Jensen et al., 1956). Absorption of sera from people of twenty 

 years of age with the PR8 strain removes antibody to all other type A strains; 

 all antibody in the serum of persons of thirty to fifty years is absorbed by 

 swine influenza virus; all antibody is absorbed from children's serum by 

 A-prime strains. These effects were substantiated by observations in ferrets 

 successively infected with three serologically different strains of type A virus. 

 Absorption of the serum after the third infection with the second or third 

 strain removed antibody to that strain and to some cross-related antigens, 

 but when the serum was absorbed with the first infecting strain, antibody to 



