Abstract：
:Generation of potent antibodies by a mutation-selection process called affinity maturation is a key component of effective immune responses. Antibodies that protect against highly mutable pathogens must neutralize diverse strains. Developing effective immunization strategies to drive their evolution requires understanding how affinity maturation happens in an environment where variants of the same antigen are present. We present an in silico model of affinity maturation driven by antigen variants which reveals that induction of cross-reactive antibodies often occurs with low probability because conflicting selection forces, imposed by different antigen variants, can frustrate affinity maturation. We describe how variables such as temporal pattern of antigen administration influence the outcome of this frustrated evolutionary process. Our calculations predict, and experiments in mice with variant gp120 constructs of the HIV envelope protein confirm, that sequential immunization with antigen variants is preferred over a cocktail for induction of cross-reactive antibodies focused on the shared CD4 binding site epitope.
journal_name
Celljournal_title
Cellauthors
Wang S,Mata-Fink J,Kriegsman B,Hanson M,Irvine DJ,Eisen HN,Burton DR,Wittrup KD,Kardar M,Chakraborty AKdoi
10.1016/j.cell.2015.01.027subject
Has Abstractpub_date
2015-02-12 00:00:00pages
785-797issue
4eissn
0092-8674issn
1097-4172pii
S0092-8674(15)00070-7journal_volume
160pub_type
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