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. 1966 Sep 1;124(3):331–345. doi: 10.1084/jem.124.3.331

DISQUISITIONS ON ORIGINAL ANTIGENIC SIN

I. EVIDENCE IN MAN

S Fazekas de StGroth 1, R G Webster 1
PMCID: PMC2138235  PMID: 5922742

Abstract

When primary immunity is boosted not by the homologous but by a crossreacting vaccine, the newly formed antibodies react better with the primary antigen than with the antigen actually eliciting the response. This phenomenon bears the name of Original Antigenic Sin (1). It is shown that the number of antibody molecules produced against the original and the vaccinating antigen is the same; that each of these molecules is capable of reacting with both antigens; that the activity of an antiserum can be completely absorbed with either antigen; that both residual and adsorbed-dissociated fractions of antibody exhibit the same relative affinities towards the two antigens as did the native serum; that, unlike standard primary and secondary responses, the population of antibody molecules characterizing the Original Antigenic Sin is homogeneous; that each molecule has a lower equilibrium constant (i.e. higher avidity) against the original antigen than against the antigen stimulating the present response; and that all equilibrium constants are typical of secondary antibody. It is concluded that the Original Antigenic Sin is a partial anamnestic response, a related antigen stimulating that sector only of the originally primed cells which is destined to produce cross-reacting antibody. A hypothesis is developed according to which the basic difference between primary and secondary reactivity rests on the presence of a trapping mechanism that allows anamnestic production of antibody against lower doses of the homologous antigen. Such a mechanism is capable of cross-trapping related antigens, thus preventing a standard primary response and allowing manifestations of Original Antigenic Sin.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. ARONSSON T., GRONWALL A. Improved separation of serum proteins in paper electrophoresis: a new electrophoresis buffer. Scand J Clin Lab Invest. 1957;9(4):338–341. doi: 10.1080/00365515709079983. [DOI] [PubMed] [Google Scholar]
  2. BOYDEN S. V. Antibody production. Nature. 1960 Mar 12;185:724–727. doi: 10.1038/185724a0. [DOI] [PubMed] [Google Scholar]
  3. CAMPBELL J. G. Anamnestic responses in rabbits immunized with two related bacterial viruses. Aust J Exp Biol Med Sci. 1959 Jun;37:245–252. doi: 10.1038/icb.1959.25. [DOI] [PubMed] [Google Scholar]
  4. DAVENPORT F. M., HENNESSY A. V. A serologic recapitulation of past experiences with influenza A; antibody response to monovalent vaccine. J Exp Med. 1956 Jul 1;104(1):85–97. doi: 10.1084/jem.104.1.85. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. DAVENPORT F. M., HENNESSY A. V., FRANCIS T., Jr Epidemiologic and immunologic significance of age distribution of antibody to antigenic variants of influenza virus. J Exp Med. 1953 Dec;98(6):641–656. doi: 10.1084/jem.98.6.641. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. DAVENPORT F. M., HENNESSY A. V. Predetermination by infection and by vaccination of antibody response to influenza virus vaccines. J Exp Med. 1957 Dec 1;106(6):835–850. doi: 10.1084/jem.106.6.835. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. EISEN H. N., KARUSH F. IMMUNE TOLERANCE AND AN EXTRACELLULAR REGULATORY ROLE FOR BIVALENT ANTIBODY. Nature. 1964 May 16;202:677–682. doi: 10.1038/202677a0. [DOI] [PubMed] [Google Scholar]
  8. FISHMAN M., ADLER F. L. Antibody formation initiated in vitro. II. Antibody synthesis in x-irradiated recipients of diffusion chambers containing nucleic acid derived from macrophages incubated with antigen. J Exp Med. 1963 Apr 1;117:595–602. doi: 10.1084/jem.117.4.595. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. FISHMAN M. Antibody formation in vitro. J Exp Med. 1961 Dec 1;114:837–856. doi: 10.1084/jem.114.6.837. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. FRANCIS T., Jr, DAVENPORT F. M., HENNESSY A. V. A serological recapitulation of human infection with different strains of influenza virus. Trans Assoc Am Physicians. 1953;66:231–239. [PubMed] [Google Scholar]
  11. FRANCIS T., Jr Influenza: the new acquayantance. Ann Intern Med. 1953 Aug;39(2):203–221. doi: 10.7326/0003-4819-39-2-203. [DOI] [PubMed] [Google Scholar]
  12. FRANCIS T., Jr The current status of the control of influenza. Ann Intern Med. 1955 Sep;43(3):534–538. doi: 10.7326/0003-4819-43-3-534. [DOI] [PubMed] [Google Scholar]
  13. HENNESSY A. V., DAVENPORT F. M., FRANCIS T., Jr Studies of antibodies to strains of influenza virus in persons of different ages in sera collected in a postepidemic period. J Immunol. 1955 Nov;75(5):401–409. [PubMed] [Google Scholar]
  14. JENSEN K. E., DAVENPORT F. M., HENNESSY A. V., FRANCIS T., Jr Characterization of influenza antibodies by serum absorption. J Exp Med. 1956 Aug 1;104(2):199–209. doi: 10.1084/jem.104.2.199. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. NISONOFF A., PRESSMAN D. Heterogeneity and average combining constants of antibodies from individual rabbits. J Immunol. 1958 Jun;80(6):417–428. [PubMed] [Google Scholar]
  16. NISONOFF A., PRESSMAN D. Heterogeneity of antibody sites in their relative combining affinities for structurally related haptens. J Immunol. 1958 Aug;81(2):126–135. [PubMed] [Google Scholar]

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