title: Primary vaccine failure to routine vaccines: Why and what to do?
abstract: There are 2 major factors responsible for vaccine failures, the first is vaccine-related such as failures in vaccine attenuation, vaccination regimes or administration. The other is host-related, of which host genetics, immune status, age, health or nutritional status can be associated with primary or secondary vaccine failures. The first describes the inability to respond to primary vaccination, the latter is characterized by a loss of protection after initial effectiveness. Our studies concentrate on the evaluation of immunological characteristics responsible for primary vaccine failures in different (risk) populations for which the underlying mechanisms are currently unknown. Here we summarise current knowledge and findings from our studies. About 2-10% of healthy individuals fail to mount antibody levels to routine vaccines. Comparing the immune responses to different vaccines in non-responder and high-responder vaccinees revealed that hypo-responsiveness is antigen/vaccine-specific at the humoral but not at the cellular level. We found that T-regulatory as well as B-regulatory cells and the production of IL-10 are involved in non/hypo-responsiveness. Non-responsiveness increases with age and in particular vaccination to a novel vaccine in persons > 65 years is associated with a high low/non-responder rate, indicating that vaccine schedules and doses (at least for primary vaccination) should be adapted according to age. In light of the growing number of allergic but also obese people, our current studies concentrate on these risk groups to reveal whether different vaccination approaches are necessary for optimal protection compared to healthy individuals. These studies are in line with the significant paradigm shift taking place in many fields of medical research and care, and will extend the concept of personalised medicine into the field of vaccinology.
authors.affiliation: a Institute of Specific Prophylaxis and Tropical Medicine; Medical University Vienna ; Vienna , Austria.
authors.forename: Ursula
authors.initials: U
authors.lastname: Wiedermann
authors.affiliation: a Institute of Specific Prophylaxis and Tropical Medicine; Medical University Vienna ; Vienna , Austria.
authors.forename: Erika
authors.initials: E
authors.lastname: Garner-Spitzer
authors.affiliation: a Institute of Specific Prophylaxis and Tropical Medicine; Medical University Vienna ; Vienna , Austria.
authors.forename: Angelika
authors.initials: A
authors.lastname: Wagner
mesh_terms: D060151:B-Lymphocytes, Regulatory / Q000276:immunology; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D017211:Treatment Failure; D014612:Vaccines / Q000008:administration & dosage* / Q000276:immunology*
chemical_list: C508609:IL10 protein, human; D014612:Vaccines; D016753:Interleukin-10
keywords: antibody; failure; immunisation; personalised; protection; response; vaccination; vaccinology
references.citation: J Immunol. 2013 Sep 1;191(5):2426-36
references.pmid: 23872054
references.citation: Exp Gerontol. 2014 Jun;54:94-100
references.pmid: 24370373
references.citation: PLoS One. 2012;7(3):e34145
references.pmid: 22461903
references.citation: Vaccine. 2013 Jan 11;31(4):584-90
references.pmid: 23142301
references.citation: Lancet. 1999 Jan 16;353(9148):196-200
references.pmid: 9923875
references.citation: Nat Immunol. 2013 May;14(5):428-36
references.pmid: 23598398
references.citation: Int J Med Microbiol. 2006 May;296 Suppl 40:202-7
references.pmid: 16524776
references.citation: PLoS One. 2013 Dec 11;8(12):e82779
references.pmid: 24349359
references.citation: Chest. 2014 Nov;146(5):1347-57
references.pmid: 25367471
references.citation: Vaccine. 2007 Jan 15;25(5):927-31
references.pmid: 17005304
references.citation: Exp Gerontol. 2008 Jan;43(1):34-8
references.pmid: 17977683
references.citation: J Infect Dis. 2002 Jan 1;185(1):114-7
references.pmid: 11756990
references.citation: J Comp Pathol. 2010 Jan;142 Suppl 1:S116-9
references.pmid: 19959180
references.citation: Diabetes Res Clin Pract. 2005 Jul;69(1):29-35
references.pmid: 15955385
references.citation: Vaccine. 2005 Jul 14;23(32):4158-66
references.pmid: 15964484
references.citation: Klin Wochenschr. 1986 Aug 1;64(15):688-94
references.pmid: 2945040
references.citation: Vaccine. 2005 May 9;23(25):3232-5
references.pmid: 15837226
references.citation: Clin Infect Dis. 2011 Jul 1;53(1):68-75
references.pmid: 21653306
references.citation: J Med Virol. 2012 Aug;84(8):1274-8
references.pmid: 22711356
references.citation: Int J Obes (Lond). 2012 Aug;36(8):1072-7
references.pmid: 22024641
references.citation: Vaccine. 2006 Nov 17;24(47-48):6808-11
references.pmid: 16872725
references.citation: Autoimmunity. 2006 Mar;39(2):137-41
references.pmid: 16698670
references.citation: Vaccine. 2013 Feb 18;31(9):1293-7
references.pmid: 23306371
references.citation: Exp Gerontol. 2012 Aug;47(8):654-7
references.pmid: 22564865
references.citation: Nat Rev Immunol. 2009 Mar;9(3):185-94
references.pmid: 19240757
references.citation: N Engl J Med. 1986 May 22;314(21):1393
references.pmid: 2939347
references.citation: Commun Dis Public Health. 2003 Jun;6(2):106-12
references.pmid: 12889288
references.citation: Arthritis Rheumatol. 2015 Feb;67(2):582-3
references.pmid: 25418753
references.citation: Vaccine. 2010 Apr 30;28(20):3511-5
references.pmid: 20332047
references.citation: Exp Biol Med (Maywood). 2010 Dec;235(12):1412-24
references.pmid: 21127339
references.citation: Pediatr Blood Cancer. 2011 Dec 15;57(7):1104-8
references.pmid: 21953691
references.citation: EMBO Rep. 2007 Mar;8(3):220-3
references.pmid: 17304236
references.citation: Pediatr Allergy Immunol. 2005 Dec;16(8):637-40
references.pmid: 16343084
references.citation: Arch Intern Med. 1996 Oct 28;156(19):2226-31
references.pmid: 8885822
references.citation: Sci Transl Med. 2013 May 15;5(185):185ps8
references.pmid: 23677590
references.citation: Immunol Lett. 2014 Nov;162(1 Pt B):346-53
references.pmid: 24960535
references.citation: Vaccine. 2009 Jan 7;27(2):197-204
references.pmid: 18996424
references.citation: Vaccine. 2013 Dec 16;31(52):6177-84
references.pmid: 24176495
references.citation: J Viral Hepat. 1998 Nov;5 Suppl 2:9-11
references.pmid: 9857354