SEROLOGICAL VARIATION 263 



all three strains was removed. The first experience with a type A influenza 

 virus conditions the antibody-forming mechanisms so that the related antigens 

 in strains of all subsequent experiences stimulate antibody of the initial 

 character, which then represents the age group throughout its life. With 

 increasing age, characteristic strain antigen is less apparent in the antibody 

 response to infection or vaccination because antibody to most of the antigens 

 is already present and a broader response takes place. This apparently 

 provides a resistance which is reflected in the reduced age incidence in older 

 persons to all epidemics of influenza A. One important observation is that 

 conditioning to antigens not represented in the antibody content of an age 

 group can be established by vaccination with appropriate strains (Davenport 

 and Hennessy, 1956). Subsequent inoculations or exposure will result in 

 enhancement of that antibody as well as to the first antibody acquired 

 naturally. Antibody patterns can thus be developed in all age segments of the 

 population to provide a broad coverage against numerous antigens and 

 strains. These observations have led to formulation of the doctrine of 

 "original antigenic sin" (Francis, 1955; Davenport and Hennessy, 

 1956). 



The 1957 Asian strains of type A differ distinctly from those of the last 

 twenty-five years, and antibodies to them are not found in most of the 

 population. However, as originally observed by Mulder (1957; Mulder and 

 Masurel, 1958) and repeatedly confirmed, persons of seventy to eighty years 

 of age may have antibodies to them. This indicates that the Asian strain had 

 been in circulation some seventy years ago, which would approximate the 

 time of the 1889-90 epidemic. Moreover, persons above forty especially 

 above seventy, respond to vaccination with Asian strains by better antibody 

 production to that dominant antigen than do younger age groups. Some 

 produce antibody to Asian virus after vaccination with heterologous strains 

 (Davenport, 1958). The incidence of disease has been distinctly lower in the 

 population over forty years. Antibody to the 1957 strains apparently 

 typifies the oldest age group and will hereafter be typical as well of that 

 population cohort which is now in the early years of life. 



3. Classification of Type A Strains 



The accumulated information from serological studies of influenza A virus 

 provides a reasonable basis for separation of the strains into four groups, 

 each representing a period of epidemic prevalence. They constitute major 

 mutations, but in each instance their dominant antigens have been shown to 

 be related to strains dispersed in other years. Genetic controls appear to keep 

 them within the type boundaries rather than following an unrestricted 

 course of developing totally new species. (Table III). 



