Modeling the effects of prior infection on vaccine efficacy

We performed computer simulations to study the effects of prior infection on vaccine efficacy. We injected three antigens sequentially. The first antigen, designated the prior, represented a prior infection or vaccination. The second antigen, the vaccine, represented a single component of the trivalent influenza vaccine. The third antigen, the epidemic, represented challenge by an epidemic strain. For a fixed vaccine to epidemic strain cross-reactivity, we generated prior strains over a full range of cross-reactivities to the vaccine and to the epidemic strains. We found that, for many cross-reactivities, vaccination, when it had been preceded by a prior infection, provided more protection than vaccination alone. However, at some cross-reactivities, the prior infection reduced protection by clearing the vaccine before it had the chance to produce protective memory. The cross-reactivities between the prior, vaccine and epidemic strains played a major role in determining vaccine efficacy. This work has applications to understanding vaccination against viruses such as influenza that are continually mutating.

[1]  G Köhler,et al.  Frequency of precursor cells against the enzyme β‐galactosidase An estimate of the BALB/c strain antibody repertoire , 1976, European journal of immunology.

[2]  N. K. Jerne,et al.  Clonal selection in a lymphocyte network. , 1974, Society of General Physiologists series.

[3]  G M Edelman,et al.  Origins and mechanisms of specificity in clonal selection. , 1974, Society of General Physiologists series.

[4]  Sylvia Deutsch,et al.  Original antigenic sin at the cellular level I. Antibodies produced by individual cells against cross‐reacting haptens , 1972, European journal of immunology.

[5]  P E Seiden,et al.  A model for simulating cognate recognition and response in the immune system. , 1992, Journal of theoretical biology.

[6]  Ron R. Hightower,et al.  Deriving shape space parameters from immunological data. , 1997, Journal of theoretical biology.

[7]  Thomas Francis,et al.  EPIDEMIOLOGIC AND IMMUNOLOGIC SIGNIFICANCE OF AGE DISTRIBUTION OF ANTIBODY TO ANTIGENIC VARIANTS OF INFLUENZA VIRUS , 1953, The Journal of experimental medicine.

[8]  R. Webster,et al.  Disquisitions of Original Antigenic Sin. I. Evidence in man. , 1966, The Journal of experimental medicine.

[9]  N. Cox,et al.  Antigenic drift in influenza virus H3 hemagglutinin from 1968 to 1980: multiple evolutionary pathways and sequential amino acid changes at key antigenic sites , 1983, Journal of virology.

[10]  A. Wilson,et al.  Immunological comparison of azurins of known amino acid sequence , 1975, Journal of Molecular Evolution.