Vaccines and the Role of Pre-existing Immunity
المؤلف:
Sunil Thomas
المصدر:
Vaccine Design: Methods and Protocols: Volume 1:Vaccines for Human Diseases
الجزء والصفحة:
p114-115
2025-05-26
545
Immune systems are typically not neutral as they have previously encountered foreign agents and have built tolerance to self- components. Furman et al. and others have shown that pre- existing titers against influenza hemagglutinin reduce effectiveness of the trivalent inactivated seasonal influenza vaccine (TIV) in terms of total HA-neutralizing (HAI) titer achieved [ 1 , 2 ]. This effect does not seem to exist for an influenza live vaccine (LAIV) [ 3 ].
Current evidence suggests possible detrimental role of low- affinity antibodies stemming from previous infections with related pathogens as demonstrated in Dengue virus infection. Infection by a single serotype is in most cases harmless, or comparable to infection as in common cold. However, infection by three or four serotypes frequently leads to a hemorrhagic syndrome, inducing cross-reactive T-cells and (low-affinity) antibody-mediated enhancement (ADE) [ 4 – 5 ].
An example where pre-existing immunity against the vaccine vector increases pathogen acquisition rates is Merck’s MRKAd5/ HIV which is highly immunogenic but non-efficacious. This HIV - 1 vaccine uses an inactivated adenovirus serotype 5 (Ad5) vaccine vector and seems to induce high HIV - 1 infection rates in Ad5 seropositive individuals [ 6 ]. While reason behind this effect has been suggested to be at least in part antibody-mediated uptake leading to increased dendritic cell activation, recent systems analysis by Zak et al. suggests that pre-existing Ad5-neutralizing antibodies effectively reduce dose of vaccine and hence immunogenicity [ 7 , 8 ].
It is also well established that stimulating the immune system in a way as to promote an immune arm unsuitable for pathogen clearance can be an immuno-evasive strategy for pathogens, exemplarily demonstrated by the Th1 versus Th2 immune signatures seen in leprosy and the role of IL-10 in Epstein - Barr virus EBV ) infection [ 9 , 10 ]. The induced state of the immune system and degree of cross-reactivity of the adaptive immune system can be expected to severely shape efficacy and precise nature the host responds to secondary natural infections and also to vaccines [ 11 – 12 ]. Better understanding of the precise interaction of superinfections and interaction of complex immune phenotypes with vaccines may contribute substantially to prediction of inter-patient variability in vaccine responses. This calls for advances in immunology , molecular biology, and systems vaccinology.
References
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[2] He X-S, Holmes TH, Sasaki S et al (2008) Baseline levels of influenza-specific CD4 memory T-cells affect T-cell responses to influenza vaccines. PLoS One 3:e2574
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[6] McElrath MJ, De Rosa SC, Moodie Z et al (2008) HIV-1 vaccine-induced immunity in the test-of-concept Step Study: a case-cohort analysis. Lancet 372:1894–1905
[7] Perreau M, Pantaleo G, Kremer EJ (2008) Activation of a dendritic cell–T cell axis by Ad5 immune complexes creates an improved environment for replication of HIV in T cells. J Exp Med 205:2717–2725
[8] Zak DE, Andersen-Nissen E, Peterson ER et al (2012) Merck Ad5/HIV induces broad innate immune activation that predicts CD8+ T-cell responses but is attenuated by preexisting Ad5 immunity. Proc Natl Acad Sci U S A 109:E3503–E3512
[9] Nath I, Saini C, Valluri VL (2015) Immunology of leprosy and diagnostic challenges. Clin Dermatol 33:90–98
[10] Lindquester GJ, Greer KA, Stewart JP, Sample JT (2014) Epstein-Barr virus IL-10 gene expression by a recombinant murine gammaherpesvirus in vivo enhances acute pathogenicity but does not affect latency or reactivation. Herpesviridae 5:1
[11] Rawson TM, Anjum V, Hodgson J et al (2014) Leprosy and tuberculosis concomitant infection: a poorly understood, age-old relationship. Lepr Rev 85:288–295
[12] Coffey LL, Failloux A-B, Weaver SC (2014) Chikungunya virus-vector interactions. Viruses 6:4628–4663
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