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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[1] Beyer WE, de Bruijn IA, Palache AM et al (1999) Protection against influenza after annually repeated vaccination: a meta-analysis of serologic and fi eld studies. Arch Intern Med 159:182–188

[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

[3] Sasaki S, He X-S, Holmes TH et al (2008) Influence of prior influenza vaccination on antibody and B-cell responses. PLoS One 3:e2975

[4] Schmid MA, Diamond MS, Harris E (2014) Dendritic cells in dengue virus infection: tar gets of virus replication and mediators of immunity. Front Immunol 5:647

[5] Mustafa MS, Rasotgi V, Jain S, Gupta V (2015) Discovery of fifth serotype of dengue virus (DENV-5): a new public health dilemma in dengue control. Med J Armed Forces India 71:67–70

[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

مواضيع ذات صلة

Microbiota, Chronic Infections, and Vaccines

Examples of Protein Subunit Vaccines

Methods for Using Full-Length Antigens (Proteins) as Vaccines

Pan-Genomic Analysis

Reverse Vaccinology

Improving Vaccines over Natural Immune Responses

Selecting Vaccine Antigens

Principles of Vaccine Development

A Brief History of Vaccination

Development of Vaccines for Tuberculosis and Meningitis

Development of Vaccines for Viral Hepatitis, Coronavirus, and Norovirus

Development of Powerful Influenza Vaccines