Modern approaches to vaccination in children with different types of primary and secondary immunodeficiencies (literature review)




children, primary immunodeficiencies, antibody deficiency, immunosuppressive therapy, infectious diseases


Chronic disease and immunosuppression increase the risk of vaccine-preventable infections, complications, and mortality from infectious diseases. Safe vaccination and achieving an adequate serological response to vaccination are crucial aspects of the management of such patients.

Purpose - to analyze data from domestic and foreign medical literature regarding modern approaches to vaccination of children with various primary and secondary immunodeficiency diseases.

The majority of children with primary immunodeficiency who have preserved antibody production can demonstrate an immune response to vaccination, but this response can be rapidly lost over time. Limitations to vaccinating children with primary immunodeficiency are related to the use of live vaccines in conditions where the cellular immune system is compromised.

Patients with primary antibody deficiency are treated with immunoglobulin preparations and depend on the presence of specific antibodies at a protective level against infectious pathogens, including vaccine-preventable infections. Several studies have shown the effectiveness of intravenous immunoglobulin treatment in reducing the number and severity of infections in patients with humoral deficiency.

The majority of children with rheumatic diseases vaccinated according to the Schedule of Routine Immunisations before starting immunosuppressive therapy have protective antibody levels against vaccine-preventable infections. All non-live vaccines can be administered without restrictions, but should be administered two weeks before immunosuppressive therapy to increase immunogenicity. Children receiving high doses of immunosuppressive therapy should avoid receiving live attenuated vaccines.

No conflict of interests was declared by the author.


Albert D, Dunham J, Khan S et al. (2008). Variability in the biological response to anti- CD20 B cell depletion in systemic lupus erythaematosus. Ann Rheum Dis. 67: 1724-1731.; PMid:18250115

Au K, Reed G, Curtis JR et al. (2011). High disease activity is associated with an increased risk of infection in patients with rheumatoid arthritis. Ann Rheum Dis. 70: 785-791.; PMid:21288960

Beglaryan SA, Chernyshova LI. (2018). Approaches to the development of clinical criteria for cases suspicious for primary immunodeficiency (literature review). Sovremennaya pediatriya. 8(96): 92-98.

Bergbreiter A, Salzer U. (2009). Common variable immunodeficiency: a multifaceted and puzzling disorder. Expert. Rev. Clin. Immunol. 5(2): 167-180.; PMid:20477064

Bernatowska E, Wolska-Kusnierz B, Pac M et al. (2007). Risk of BCG infection in primary immunodeficiency children. Proposal of diagnostic, prophylactic and herapeutic guidelines for disseminated BCG based on experience in the Department of Immunology. Children's Memorial Health Institute in Warsaw between 1980-2006. Centr. Eur. J. Immunol. 32 (4): 221-225.

Bondarenko AV. (2015). Diagnostics of primary immunodeficiencies. Family medicine. 4(60): 154-160.

Chen N, Zhang ZY, Liu DW et al. (2015). The clinical features of autoimmunity in 53 patients with Wiskott-Aldrich syndrome in China: a single-center study. Eur. J. Pediatr. 174(10): 1311-1318.; PMid:25877044

Chernyshova LI, Volokha AP, Kostyuchenko LV. (2013). Pediatric immunology: a textbook. Kyiv: VSV Medicine: 720.

Chernyshova LI. (2006). Primary immunodeficiencies in children. Art of healing. 2: 16-21.

Chernyshova LI. (2007). Problems and achievements of pediatric clinical immunology in Ukraine in 2006. Perinatology and pediatrics. 3(31): 5-6.

Compagno N, Malipiero G, Cinetto F, Agostini C. (2014, Dec 08). Immunoglobulin replacement therapy in secondary hypogammaglobulinemia. Frontiers in Immunology. 5(626): 1-6.; PMid:25538710 PMCid:PMC4259107

Dmytruk VI, Zaslavska HO. (2017). Imunoprofilaktyka infektsiinykh zakhvoriuvan u ditei: dosiahnennia ta problemy. Antyvaktsynalnyi rukh yak faktor pereshkody v provedenni imunizatsiinaselennia. Aktualna infektolohiia. 5 (4): 166-171.

Farcet MR, Planitzer CB, Stein O, Modrof J, Kreil TR. (2010). Hepatitis A virus antibodies in immunoglobulin preparations. J Allergy Clin Immunol. 125(1): 198-202.; PMid:19962745

Firinu D, Massida O, Lorrai MM et al. (2011). Successful Treatment of Chronic Mucocutaneous Candidiasis Caused by Azole-Resistant Candida albicans with Posaconazole. Clinical and Developmental Immunology. Article ID 283239.; PMid:21197459 PMCid:PMC3003968

Furer V, Rondaan C, Heijstek MW, Agmon-Levin N, van Assen S, Bijl M et al. (2020). 2019 Update of EULAR Recommendations for Vaccination in AdultPatients with Autoimmune Inflammatory Rheumatic Diseases. Ann RheumDis. 79(1): 39-52.; PMid:31413005

Germano V, Cattaruzza MS, Osborn J et al. (2014). Infection risk in rheumatoid arthritis and spondyloarthropathy patients under treatment with DMARDs, corticosteroids and TNF-α antagonists. J Transl Med. 12: 77.; PMid:24655394 PMCid:PMC3994399

Goyal R, Bulua AC, Nikolov NP et al. (2009). Rheumatologic and autoimmune manifestations of primary immunodeficiency disorders. Curr. Opin. R. 21(1): 78-84.; PMid:19077721 PMCid:PMC2760066

Guo LI, Chen BO, Xu B et al. (2015). X-linked hyper-IgM syndrome with eosinophilia in a male child: A case report. Exp. Ther. Med. 9(4): 1328-1330.; PMid:25780430 PMCid:PMC4353739

Guthridge JM, Cogman A, Merrill JT et al. (2013). Herpes zoster vaccination in SLE: a pilot study of immunogenicity. J Rheumatol. 40: 1875-1880.; PMid:24037550 PMCid:PMC3867792

Hellerud BC, Aase A, Herstad TK et al. (2010). Critical roles of complement and antibodies in host defense mechanisms against Neisseria meningitidis as revealed by human complement genetic deficiencies. Infect Immun. 78(2): 802-809.; PMid:19933829 PMCid:PMC2812193

Husebye ES, Perheentupa J, Rautemaa R, Ksmpe O. (2019). Clinical manifestations and management of patients with autoimmune polyendocrine syndrome type I. J. Intern. Med. 265: 514-529.; PMid:19382991

Kobrynski LJ, Sulivan KE. (2007). Velocardiofacial syndrome, DiGeorge syndrome: the chromosome 22g11.2 deletion syndromes. Lancet. 370 (9596): 1443-1452.; PMid:17950858

Kostik MM, Lubimova NA, Fridman IV et al. (2021). The vaccinecoverage and vaccine immunity status and risk factors of non protective levels of antibodies against vaccines in children withjuvenile idiopathic arthritis: cross-sectional Russian tertiary Centre study. Pediatric Rheumatology. 19(1): 108.; PMid:34225748 PMCid:PMC8256221

Kostyuchenko LV, Romanashyn YaYu. (2010). Autoimmune phenomena in children with primary immunodeficiencies. Pediatrics, obstetrics and gynecology: science and practice journal. 72 (5): 41-44.

Lee PP, Woodbine L, Gilmour KC, Bibi S, Cale CM, Amrolia PJ et al. (2013). The manyfaces of Artemis-deficient combined immunodeficiency: Two patients with DCLRE1C mutations and a systematic literaturereview of genotype-phenotype correlation. Clin. Immunol. 149: 464-474.; PMid:24230999

Lucas M, Lee M, Lortan J, Lopez-Granados E, Misbah S, Chapel H. (2010). Infection outcomes in patients with common variable immunodeficiency disorders: relationship to immunoglobulin therapy over 22 years. J Allergy Clin Immunol. 125(6): 1354-1360.; PMid:20471071

Melony A, Willcox N, Meager A et al. (2012). Autoimmune polyendocrine syndrome type 1: an extensive longitudinal study in Sardinian patients. J. Clin. Endocr. Metab. 97: 1114-1124.; PMid:22344197

Nobre FA, Gonzalez IG, Simao RM et al. (2014). Antibody levels to tetanus, diphtheria, measles and varicella in patients with primary immunodeficiency undergoing intravenous immunoglobulin therapy: a prospective study. BMC Immunology. 15: 26.; PMid:24952415 PMCid:PMC4074853

Omelchenko LI, Oshlyanska OA. (2011). Immunopathological mechanisms of development of rheumatic diseases in children as a basis for choosing treatment tactics. Nowadays Pediatrics. 1: 135-141.

Oshlyanska OA, Omelchenko LI, Chernyshov VP, Galazyuk LV. (2008). The role of a nonspecific cellular immune response in the formation of autoimmunity. Perinatology and pediatrics. 3: 83-85.

Patel SY, Carbone J, Jolles S. (2019, Feb 08). The Expanding Fieldof Secondary Antibody Deficiency: Causes, Diagnosis, and Management. Frontiers in Immunology. 10(33): 1-15.; PMid:30800120 PMCid:PMC6376447

Pochynok TV, Omelchenko LI. (2004). Selective Ig A deficiency and chronic fatigue syndrome. Perinatologiya i pediatriya. 1: 33-35.

Puel A, Doffinger R, Natividad A. (2010). Autoantibodies against IL-17A, IL-17F and IL-22 in patients with chronic mucocutaneous candidiasis and autoimmune polyendocrine syndrome type I. J. Exp. Med. 207(2): 291-297.; PMid:20123958 PMCid:PMC2822614

Quinti I, Soresina A, Guerra A, Rondelli R, Spadaro G, Agostini C et al. (2011). IPINet Investigators. Effectiveness of immunoglobulin replacement therapy on clinical outcome in patients with primary antibody deficiencies: results from a multicenter prospective cohort study. J Clin Immunol. 31(3): 315-322.; PMid:21365217

Rehnberg M, Amu S, Tarkowski A, Bokarewa MI, Brisslert M. (2009). Short- and Long-Term Effects of Anti-CD20 Treatment on B Cell Ontogeny in BoneMarrow of Patients With Rheumatoid Arthritis. Arthritis Res Ther. 11(4): R123.; PMid:19686595 PMCid:PMC2745807

Romanyshin YYu, Kostyuchenko LV, Vygovska LS. (2011). X-linked lymphoproliferative syndrome. Sovremennaya pediatriya. 2: 179-182.

Shah I, Rahangdale A, Bhatnagar S. (2013). Liver Abscesses and Hyper IgM Syndrome. J. Family Med. Prim. Care. 2(2): 206-208.; PMid:24479081 PMCid:PMC3894042

Soler-Palacin P, Margareto C, Llobet P et al. (2007). Chronic granulomatous disease in pediatric patients: 25 years of experience. Allergol. Immunopathol. (Madr). 35 (3): 83-89.; PMid:17594870

Srivastava S, Wood P. (2016). Secondary antibody deficiency - causes and approach to diagnosis. Clin Med. 16: 571-576.; PMid:27927823 PMCid:PMC6297325

Srivastava S, Wood P. (2016, Dec). Secondary antibody deficiency - causes and approach to diagnosis. Clinical Medicine. 16(6): 571-576.; PMid:27927823 PMCid:PMC6297325

Subbarayan A, Colarusso G, Hughes SM et al. (2011). Clinical Features That Identify Children with Primary Immunodeficiency Diseases. Pediatrics. 127: 800-816.; PMid:21482601

Voloha AP. (2019). Vaktsinatsiya detey s hronicheskimi zabolevaniyami. Pediatriya. Vostochnaya Evropa. 7 (4): 644-660.

Volokha AP, Boiarchuk OR, Bondarenko AV. (2020). Vaktsynatsiia ditei z pervynnymy imunodefitsytamy. Metodychni rekomendatsii. Kyiv: Znannia.

Volokha AP, Chernyshova LI. (2010). Rol imunizatsii v zakhystivid infektsii osib z pervynnymy imunodefitsytamy. Sovremennaya pedyatriya. 2: 140-145.

Volokha AP, Chernyshova LI. (2010). Rol imunizatsii v zakhysti vid infektsii osib z pervynnymy imunodefitsytamy. Sovremennaya pediatriya. 2: 140-145.

Volokha AP, Chernyshova LY, Berezhnoi VV. (2005). Juvenile rheumatoid arthritis in a patient with hereditary hypogammaglobulinemia. Sovremennaya pediatriya. 4(9): 180-184.

Volokha AP. (2019). Vaccination of children with chronic diseases. Pediatrics. Eastern Europe. 7 (4): 644-660.

Wang LL, Zhou W, Zhao W et al. (2014). Clinical features and genetic analysis of 20 Chinese patients with X-linked hyper-IgM syndrome. J. Immunol. Res. 2014: 683160. Epub 2014 Aug 20.; PMid:25215306 PMCid:PMC4158165

Weaver A, Troum O, Hooper M et al. (2013). Rheumatoid arthritis disease activity and disability affect the risk of serious infection events in radius 1. J Rheumatol. 40: 1275-1281.; PMid:23772079

Yarmohammadi H, Estrella L, Doucette J et al. (2006). Recognizing primary immune deficiency in clinical practice. Clin. Vaccine Immunol. 13(3): 329-332.; PMid:16522773 PMCid:PMC1391953