{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:42:27Z","timestamp":1760060547380,"version":"build-2065373602"},"reference-count":50,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T00:00:00Z","timestamp":1756771200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Regione Lombardia (Milano, Italy)","award":["13465\/2013","2009"],"award-info":[{"award-number":["13465\/2013","2009"]}]},{"name":"Post-Polio Health International (St. Louis, MO, USA)","award":["13465\/2013","2009"],"award-info":[{"award-number":["13465\/2013","2009"]}]},{"name":"Eighth Award-2014","award":["13465\/2013","2009"],"award-info":[{"award-number":["13465\/2013","2009"]}]},{"name":"Associazione Interregionale Disabili Motori (AIDM), Ospedale di Malcesine (Verona, Italy)","award":["13465\/2013","2009"],"award-info":[{"award-number":["13465\/2013","2009"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Background\/Objectives: This study investigated susceptibility factors that may contribute to Post-Polio Syndrome (PPS) in elderly polio survivors. Methods: Serum immunoglobulin (Ig) levels, poliovirus neutralizing antibodies (PV NAb), and vitamin D status were evaluated in 80 PPS patients, 40 family members, and 89 healthy controls. Results: A significant number of PPS patients and their family members showed reduced levels of total IgG and\/or IgA, and specific IgG subclasses, indicating a high prevalence of primary humoral immunodeficiencies within these groups. Despite these Ig deficits, PV NAb titers were similar across all groups, indicating high protection against poliovirus, likely due to vaccination campaigns with live virus in Italy and intense exposure to poliovirus, especially in long-term rehabilitation institutions. However, a small group of PPS subjects lacked neutralizing antibodies for specific poliovirus serotypes, suggesting more severe antibody deficiencies. Additionally, PPS subjects had a high prevalence of vitamin D deficiency, which likely increases their risk for osteoporosis\/osteopenia and fractures. It is unclear if this deficiency was also present in their infancy, potentially enhancing their susceptibility to poliovirus. Conclusions: Overall, the findings indicate that genetic, immunological, or nutritional factors may increase individual susceptibility to the pathogenic effects of poliovirus. This study\u2014limited to serum antibodies\u2014highlights the complex relationship between immune status and long-term health in aging polio survivors. The results emphasize the need for potent poliovirus drugs and vaccines to help contain possible outbreaks but also\u2014for poliomyelitis survivors\u2014to avoid or mitigate the progression to PPS, the latest phase of this devastating disease.<\/jats:p>","DOI":"10.3390\/vaccines13090939","type":"journal-article","created":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T16:05:22Z","timestamp":1756829122000},"page":"939","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Post-Polio Syndrome: Impact of Humoral Immune Deficiencies, Poliovirus Neutralizing Antibodies, Vitamin D Deficiency"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3008-2126","authenticated-orcid":false,"given":"Antonio","family":"Toniolo","sequence":"first","affiliation":[{"name":"Global Virus Network, University of Insubria, 21100 Varese, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Konstantin","family":"Chumakov","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Tropical Medicine, George Washington University, Washington, DC 20052, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanni","family":"Federico","sequence":"additional","affiliation":[{"name":"Unit of Pediatrics, Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2894-3583","authenticated-orcid":false,"given":"Giuseppe","family":"Maccari","sequence":"additional","affiliation":[{"name":"Data Science for Health Lab, Fondazione Toscana Life Sciences, 53100 Siena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angelo","family":"Genoni","sequence":"additional","affiliation":[{"name":"Medical Microbiology Section, Department of Medicine, University of Insubria, 21100 Varese, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0611-5549","authenticated-orcid":false,"given":"Alessandro","family":"Saba","sequence":"additional","affiliation":[{"name":"Department of Surgical, Medical and Molecular Pathology, University of Pisa, 56126 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Nauti","sequence":"additional","affiliation":[{"name":"Clinical Laboratories, Ospedale di Circolo e Fondazione Macchi, 21100 Varese, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giorgio","family":"Bono","sequence":"additional","affiliation":[{"name":"Neurology Section, Department of Biotechnology, University of Insubria, 21100 Varese, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Franco","family":"Molteni","sequence":"additional","affiliation":[{"name":"Villa Beretta Rehabilitation Research Innovation Institute, 23845 Costa Masnaga, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3191-8597","authenticated-orcid":false,"given":"Salvatore","family":"Monaco","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, University of Verona and Policlinico GB Rossi, 37134 Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1093\/aje\/kwq320","article-title":"From Emergence to Eradication: The Epidemiology of Poliomyelitis Deconstructed","volume":"172","author":"Nathanson","year":"2010","journal-title":"Am. J. Epidemiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1038\/s41467-017-00257-5","article-title":"Genome-Wide Association and HLA Region Fine-Mapping Studies Identify Susceptibility Loci for Multiple Common Infections","volume":"8","author":"Tian","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1093\/infdis\/147.3.422","article-title":"Differential Resistance to Paralytic Poliomyelitis Controlled by Histocompatibility Leukocyte Antigens","volume":"147","author":"Persijn","year":"1983","journal-title":"J. Infect. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1002\/jmv.21444","article-title":"Ala67Thr Mutation in the Poliovirus Receptor CD155 Is a Potential Risk Factor for Vaccine and Wild-type Paralytic Poliomyelitis","volume":"81","author":"Kindberg","year":"2009","journal-title":"J. Med. Virol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/j.jaci.2018.07.013","article-title":"Lessons Learned from the Study of Human Inborn Errors of Innate Immunity","volume":"143","author":"Bucciol","year":"2019","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1111\/imr.13402","article-title":"Protective Role of Antibodies in Enteric Virus Infections: Lessons from Primary and Secondary Immune Deficiencies","volume":"328","author":"Riller","year":"2024","journal-title":"Immunol. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1016\/j.vaccine.2015.01.018","article-title":"Immunodeficiency-Related Vaccine-Derived Poliovirus (iVDPV) Cases: A Systematic Review and Implications for Polio Eradication","volume":"33","author":"Guo","year":"2015","journal-title":"Vaccine"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1016\/j.vaccine.2010.10.026","article-title":"Economic Analysis of the Global Polio Eradication Initiative","volume":"29","author":"Pallansch","year":"2010","journal-title":"Vaccine"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"S272","DOI":"10.1093\/infdis\/175.Supplement_1.S272","article-title":"Poliomyelitis Eradication and Its Impact on Primary Health Care in the Philippines","volume":"175","author":"Tangermann","year":"1997","journal-title":"J. Infect. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1086\/499970","article-title":"1,25-Dihydroxyvitamin D3 Enhances Systemic and Mucosal Immune Responses to Inactivated Poliovirus Vaccine in Mice","volume":"193","author":"Ivanov","year":"2006","journal-title":"J. Infect. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1210\/endrev\/bnae009","article-title":"Consensus Statement on Vitamin D Status Assessment and Supplementation: Whys, Whens, and Hows","volume":"45","author":"Giustina","year":"2024","journal-title":"Endocr. Rev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e055435","DOI":"10.1136\/bmjopen-2021-055435","article-title":"Vitamin D Insufficiency in COVID-19 and Influenza A, and Critical Illness Survivors: A Cross-Sectional Study","volume":"11","author":"Hurst","year":"2021","journal-title":"BMJ Open"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"110183","DOI":"10.1016\/j.clim.2024.110183","article-title":"The Immune Cell Transcriptome Is Modulated by Vitamin D3 Supplementation in People with a First Demyelinating Event Participating in a Randomized Placebo-Controlled Trial","volume":"262","author":"Yeh","year":"2024","journal-title":"Clin. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1007\/BF03349999","article-title":"Calcitriol Inhibits the PHA-Induced Production of IL-2 and IFN-\u03b3 and the Proliferation of Human Peripheral Blood Leukocytes While Enhancing the Surface Expression of HLA Class II Molecules","volume":"12","author":"Saggese","year":"1989","journal-title":"J. Endocrinol. Investig."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1038\/s41590-021-01080-3","article-title":"Autocrine Vitamin D Signaling Switches off Pro-Inflammatory Programs of TH1 Cells","volume":"23","author":"Chauss","year":"2022","journal-title":"Nat. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"r601","DOI":"10.1136\/bmj.r601","article-title":"Vitamin D for Multiple Sclerosis \u2026 and Other Research","volume":"389","author":"Nolan","year":"2025","journal-title":"BMJ"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1001\/jama.2025.1604","article-title":"High-Dose Vitamin D in Clinically Isolated Syndrome Typical of Multiple Sclerosis: The D-Lay MS Randomized Clinical Trial","volume":"333","author":"Thouvenot","year":"2025","journal-title":"JAMA"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1038\/s41579-022-00770-5","article-title":"Epstein\u2013Barr Virus and Multiple Sclerosis","volume":"21","author":"Soldan","year":"2023","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_19","unstructured":"(2025, August 29). A Multicenter, Prospective, Randomized, Placebo-Controlled, Double-Blind, Parallel-Group Clinical Trial to Assess the Efficacy and Safety of Immune Globulin Intravenous (Human) Flebogamma\u00ae 5% DIF in Patients with Post-Polio Syndrome. Available online: https:\/\/onderzoekmetmensen.nl\/en\/node\/55451\/pdf."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1111\/j.1468-1331.2006.01385.x","article-title":"EFNS Guideline on Diagnosis and Management of Post-polio Syndrome. Report of an EFNS Task Force","volume":"13","author":"Farbu","year":"2006","journal-title":"Eur. J. Neurol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1314","DOI":"10.1136\/bmj.330.7503.1314","article-title":"Poliomyelitis and the Postpolio Syndrome","volume":"330","author":"Howard","year":"2005","journal-title":"BMJ"},{"key":"ref_22","unstructured":"Rifai, N. (2022). Tietz Textbook of Laboratory Medicine, Elsevier. [7th ed.]."},{"key":"ref_23","unstructured":"World Health Organization (2021). Poliovirus Containment: Guidance to Minimize Risks for Facilities Collecting, Handling or Storing Materials Potentially Infectious for Polioviruses, WHO. [2nd ed.]."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1007\/978-1-4939-3292-4_8","article-title":"Standardized Methods for Detection of Poliovirus Antibodies","volume":"Volume 1387","year":"2016","journal-title":"Poliovirus"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1911","DOI":"10.1210\/jc.2011-0385","article-title":"Evaluation, Treatment, and Prevention of Vitamin D Deficiency: An Endocrine Society Clinical Practice Guideline","volume":"96","author":"Holick","year":"2011","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1711","DOI":"10.1016\/j.vaccine.2018.02.059","article-title":"New Insights into Physiopathology of Immunodeficiency-Associated Vaccine-Derived Poliovirus Infection; Systematic Review of over 5 Decades of Data","volume":"36","author":"Shaghaghi","year":"2018","journal-title":"Vaccine"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1080\/14740338.2024.2359616","article-title":"Vaccine-Associated Paralytic Poliomyelitis in Oral Polio Vaccine Recipients: Disproportionality Analysis Using VAERS and Systematic Review","volume":"23","author":"Suares","year":"2024","journal-title":"Expert Opin. Drug Saf."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1007\/s11882-020-00938-0","article-title":"B Cell Disorders in Children\u2014Part I","volume":"20","author":"Gilchrist","year":"2020","journal-title":"Curr. Allergy Asthma Rep."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1007\/s11882-020-00963-z","article-title":"B Cell Disorders in Children: Part II","volume":"20","author":"Griffin","year":"2020","journal-title":"Curr. Allergy Asthma Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1038\/nri3466","article-title":"Primary Antibody Deficiencies","volume":"13","author":"Durandy","year":"2013","journal-title":"Nat. Rev. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e2049","DOI":"10.1002\/rmv.2049","article-title":"Viral Infection in Primary Antibody Deficiency Syndromes","volume":"29","author":"Jones","year":"2019","journal-title":"Rev. Med. Virol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.1038\/s41590-023-01544-8","article-title":"Effect of Posttranslational Modifications and Subclass on IgG Activity: From Immunity to Immunotherapy","volume":"24","author":"Nimmerjahn","year":"2023","journal-title":"Nat. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e2107148118","DOI":"10.1073\/pnas.2107148118","article-title":"Increased in Vitro Neutralizing Activity of SARS-CoV-2 IgA1 Dimers Compared to Monomers and IgG","volume":"118","author":"Sun","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3328","DOI":"10.1038\/s41467-018-05746-9","article-title":"Deficient Humoral Responses and Disrupted B-Cell Immunity Are Associated with Fatal SFTSV Infection","volume":"9","author":"Song","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.it.2019.01.005","article-title":"Role of IgG3 in Infectious Diseases","volume":"40","author":"Damelang","year":"2019","journal-title":"Trends Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1093\/infdis\/jis033","article-title":"Early Appearance of Neutralizing Immunoglobulin G3 Antibodies Is Associated with Chikungunya Virus Clearance and Long-Term Clinical Protection","volume":"205","author":"Kam","year":"2012","journal-title":"J. Infect. Dis."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.ijid.2015.04.018","article-title":"Post-Poliomyelitis Syndrome as a Possible Viral Disease","volume":"35","author":"Baj","year":"2015","journal-title":"Int. J. Infect. Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2989","DOI":"10.1016\/j.vaccine.2021.04.005","article-title":"Long-Term Persistence of Poliovirus Neutralizing Antibodies in the Era of Polio Elimination: An Italian Retrospective Cohort Study","volume":"39","author":"Bianchi","year":"2021","journal-title":"Vaccine"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1366","DOI":"10.1080\/21645515.2020.1812315","article-title":"Safety and Immunogenicity of a New Sabin Inactivated Poliovirus Vaccine Candidate Produced on the PER.C6\u00ae Cell-Line: A Phase 1 Randomized Controlled Trial in Adults","volume":"17","author":"Shukarev","year":"2021","journal-title":"Hum. Vaccines Immunother."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"6802","DOI":"10.1016\/j.vaccine.2022.09.088","article-title":"The Fight against Poliomyelitis through the History: Past, Present and Hopes for the Future. Albert Sabin\u2019s Missing Nobel and His \u201cGift to All the World\u2019s Children\u201d","volume":"40","author":"Martini","year":"2022","journal-title":"Vaccine"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.4158\/EP-2020-0102","article-title":"The Risk of Bone Fractures in Post-Poliomyelitis Patients Transitioning to Middle Adulthood","volume":"26","author":"Sherf","year":"2020","journal-title":"Endocr. Pract."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e0146","DOI":"10.2106\/JBJS.RVW.19.00146","article-title":"Management Options and Outcomes for Patients with Femoral Fractures with Post-Polio Syndrome of the Lower Extremity: A Critical Analysis Review","volume":"8","author":"Garceau","year":"2020","journal-title":"JBJS Rev."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1080\/20469047.2023.2171759","article-title":"Vitamin D: Immune Function, Inflammation, Infections and Auto-Immunity","volume":"43","author":"Johnson","year":"2023","journal-title":"Paediatr. Int. Child Health"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1080\/17446651.2023.2270053","article-title":"Treatment of Vitamin D Deficiency in Children","volume":"18","author":"Fischer","year":"2023","journal-title":"Expert Rev. Endocrinol. Metab."},{"key":"ref_45","first-page":"783","article-title":"Poliomyelitis Control in Israel, the West Bank and Gaza Strip: Changing Strategies with the Goal of Eradication in an Endemic Area","volume":"72","author":"Goldblum","year":"1994","journal-title":"Bull. World Health Organ."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"jiw547","DOI":"10.1093\/infdis\/jiw547","article-title":"Completing Polio Eradication: The Case for Antiviral Drugs","volume":"215","author":"Sutter","year":"2016","journal-title":"J. Infect. Dis."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1177\/0272989X231191127","article-title":"Health Economic Analysis of Antiviral Drugs in the Global Polio Eradication Endgame","volume":"43","author":"Badizadegan","year":"2023","journal-title":"Med. Decis. Mak."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"105842","DOI":"10.1016\/j.antiviral.2024.105842","article-title":"The Combination of Pleconaril, Rupintrivir, and Remdesivir Efficiently Inhibits Enterovirus Infections in Vitro, Delaying the Development of Drug-Resistant Virus Variants","volume":"224","author":"Ianevski","year":"2024","journal-title":"Antivir. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1016\/S1473-3099(23)00139-1","article-title":"Immunogenicity of Novel Oral Poliovirus Vaccine Type 2 Administered Concomitantly with Bivalent Oral Poliovirus Vaccine: An Open-Label, Non-Inferiority, Randomised, Controlled Trial","volume":"23","author":"Wilkinson","year":"2023","journal-title":"Lancet Infect. Dis."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Kulkarni, P.S., Zaman, K., Desai, S.A., Bharati, S., Goswami, D.R., Sharmeen, A.T., Rana, S., Haque, W., Khandelwal, A., and Manney, S. (2025). Safety and Immunogenicity of a Reduced-Dose Inactivated Poliovirus Vaccine versus a Full-Dose Inactivated Poliovirus Vaccine in Infants in Bangladesh: A Double-Blind, Non-Inferiority, Randomised, Controlled, Phase 3 Trial. Lancet Infect. Dis.","DOI":"10.1016\/S1473-3099(25)00215-4"}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/13\/9\/939\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:37:45Z","timestamp":1760035065000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/13\/9\/939"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,2]]},"references-count":50,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["vaccines13090939"],"URL":"https:\/\/doi.org\/10.3390\/vaccines13090939","relation":{},"ISSN":["2076-393X"],"issn-type":[{"type":"electronic","value":"2076-393X"}],"subject":[],"published":{"date-parts":[[2025,9,2]]}}}