Journal
VACCINE
Volume 26, Issue 49, Pages 6189-6199Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.vaccine.2008.09.080
Keywords
Immune refocusing; Deceptive imprinting; Vaccine design
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Funding
- NIAID NIH HHS [R21 AI 44364-01, R43 AI48972-01/02, R43 AI055221-01] Funding Source: Medline
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A large number of the world's most widespread and problematic pathogens evade host immune responses by inducing strain-specific immunity to immunodominant epitopes with high mutation rates capable of altering antigenic profiles. The immune system appears to be decoyed into reacting to these immunodominant epitopes that offer little cross protection between serotypes or subtypes. For example, during HIV-1 infection, the immune system reacts strongly to the V1, V2, and/or V3 loops of the Surface envelope glycoprotein but not to epitopes that afford broad protection against strain variants. Similarly, the host mounts strain-specific immunity to immunodominant epitopes of the influenza hemagglutinin (HA) protein. A large number of pathogens appear to exploit this weakness in the host immune system by focusing antigenic attention upon highly variable epitopes while avoiding surveillance toward more highly conserved receptor binding sites or other essential functional domains. Because the propensity of the immune system to react against immunodominant strain-specific epitopes appears to be genetically hard-wired, the phenomenon has been termed deceptive imprinting. In this review, the authors describe observations related to deceptive imprinting in multiple systems and propose strategies for overcoming this phenomenon in the design of vaccines capable of inducing protection against highly variable pathogens. (C) 2008 Elsevier Ltd. All rights reserved.
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